Paola A. Gehrig, MD

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at obnews@frontlinemedcom.com.

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at obnews@frontlinemedcom.com.

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at obnews@frontlinemedcom.com.

Vulvar cancer is a rare gynecologic cancer comprising only 5% of gynecologic malignancies. Given the low incidence of disease, many primary providers and even obstetricians and gynecologists many never encounter a case. Increased awareness of vulvar cancer and vulvar dysplasia among patients and physicians may decrease diagnostic delays and expedite patient therapy.

Diagnosis

There is a well documented delay in diagnosis of vulvar cancer that is attributed to both the patient and the physician. Patients may feel uncomfortable or embarrassed telling their physicians about vulvar symptoms and providers may not recognize the risk for malignancy and provide alternative therapies prior to biopsy (J Reprod Med. 1999;44[9]:766-8.).

Risk factors for vulvar cancer include human papillomavirus (HPV) infection, a history of smoking, immunosuppression, and a history of an abnormal pap smear. Vulvar dystrophy, lichen sclerosis, and squamous intraepithelial lesions have also been suggested as precursor lesions of invasive cancers. The key to early diagnosis and treatment is immediate in-office biopsy.

When evaluating a patient with a vulvar lesion, the initial evaluation should include a thorough exam with a measurement of the lesion and evaluation of inguinal lymph nodes. Also, a detailed description of a lesion’s relationship to the midline (how many centimeters away) and other vital structures (clitoris, urethra, anus) is important.

An in-office biopsy can be done on initial presentation and should include the lesion in question and underlying stroma in an effort to delineate depth of invasion. While shave biopsies may be appropriate for some skin lesions, if there is any concern for malignancy, a punch biopsy is preferred.

Pathology

Squamous cell carcinoma is the most common histologic subtype (greater than 90%) followed by malignant melanoma. Malignant melanoma poses a diagnostic challenge as 25% may present with nonpigmented lesions. These lesions may arise from a junctional nevus and are more common in postmenopausal white women.

The measurement of tumor thickness is essential in evaluation of melanoma. A diagnosis of vulvar melanoma should be referred to a gynecologic oncologist for further evaluation and treatment. Frequently these patients require a multidisciplinary approach with other medical and surgical subspecialties consulting.

Adenocarcinoma of the vulva frequently arises within the Bartholin glands. Bartholin gland disease is typically a disease of young women. Any abscess or lesion in the bartholin gland in women older than 50 years should raise awareness of the possibility of malignancy. Providers should have a low threshold for biopsy of any Bartholin lesion in older women and for any Bartholin gland lesion or cyst that returns or persists after initial drainage.

Staging pearls

Vulvar cancer spreads by direct extension, lymphatic embolization and hematogenous spread. Lymphatic spread can occur early in the disease and portends a much worse prognosis. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system. The most significant change was in stage III disease, which now includes any patient with lymph node involvement. This change emphasizes lymph node status as the single most important prognostic factor. The 5-year overall survival of patients with locally advanced tumors but negative regional lymph nodes (62%) has been found to be significantly better than those with positive nodal status (39%, P value less than.0001) (Gynecol Oncol. 2008;110[1]:83-6.).

In patients with stage IA disease, which includes lesions less than 2 cm in size with stromal invasion of less than 1 mm, the risk of lymph node metastasis is low. These patients do not require inguinal lymph node dissection. If lesions are greater than 2 cm and/or have greater than 1 mm depth of invasion, a lymph node dissection is indicated. Lymph node dissection is performed on the ipsilateral side of the lesion as long as the lesion is more than 2 cm from a midline structure. If the lesion is in the midline or within 2 cm of the midline, a bilateral inguinal lymph node dissection is recommended.

There has been a recent uptake of the sentinel inguinal lymph node biopsy technique after two large prospective studies (the GROINSS V trial and GOG 173) validated this methodology (Lancet Oncol. 2010 Jul;11[7]:646-52 and Gynecol Oncol. 2013 Feb;128[2]:155-9).

Treatment

Surgical management of stage I and II disease involves a wide radical excision of the tumor with a 1-cm circumferential margin. Tumors with a depth of invasion of less than 1 mm do not require lymphadenectomy (Gynecol Oncol. 1992 Mar;44[3]:240-4). Stage I/II disease with deeper than 1-mm invasion requires a 2-cm margin and either sentinel node evaluation or lymphadenectomy. Survival for women with adequate resection of primary squamous carcinoma with negative lymph node involvement is greater than 90%.

Patients with metastasis to the groin frequently receive bilateral groin and pelvic radiation; however, recommendations are individualized based on size and number of metastasis. Patients should expect to receive recommendations for therapy after pathologic review and multidisciplinary consultation; therapy should be individualized for each clinical situation.

This disease is one of the elderly, but it is important to remember that treatment recommendations should not be made according to age alone. A British study found that when women over the age of 80 received standard treatment, their recurrence rate was 25% compared with a 53% recurrence rate in those whose treatment was modified (Int J Gynecol Cancer. 2009;19[4]:752-5.). In patients with advanced disease, preoperative radiation, with or without chemotherapy, is frequently regarded as the treatment of choice and may eliminate the need for radical surgery.

While vulvar cancer is a rare gynecologic malignancy, it can be devastating for patients and families, especially at late stages. Early diagnosis and treatment is imperative for improved patient outcomes. An increased awareness among patients and physicians alike may allow for earlier diagnosis and treatment.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures.

Vulvar cancer is a rare gynecologic cancer comprising only 5% of gynecologic malignancies. Given the low incidence of disease, many primary providers and even obstetricians and gynecologists many never encounter a case. Increased awareness of vulvar cancer and vulvar dysplasia among patients and physicians may decrease diagnostic delays and expedite patient therapy.

Diagnosis

There is a well documented delay in diagnosis of vulvar cancer that is attributed to both the patient and the physician. Patients may feel uncomfortable or embarrassed telling their physicians about vulvar symptoms and providers may not recognize the risk for malignancy and provide alternative therapies prior to biopsy (J Reprod Med. 1999;44[9]:766-8.).

Risk factors for vulvar cancer include human papillomavirus (HPV) infection, a history of smoking, immunosuppression, and a history of an abnormal pap smear. Vulvar dystrophy, lichen sclerosis, and squamous intraepithelial lesions have also been suggested as precursor lesions of invasive cancers. The key to early diagnosis and treatment is immediate in-office biopsy.

When evaluating a patient with a vulvar lesion, the initial evaluation should include a thorough exam with a measurement of the lesion and evaluation of inguinal lymph nodes. Also, a detailed description of a lesion’s relationship to the midline (how many centimeters away) and other vital structures (clitoris, urethra, anus) is important.

An in-office biopsy can be done on initial presentation and should include the lesion in question and underlying stroma in an effort to delineate depth of invasion. While shave biopsies may be appropriate for some skin lesions, if there is any concern for malignancy, a punch biopsy is preferred.

Pathology

Squamous cell carcinoma is the most common histologic subtype (greater than 90%) followed by malignant melanoma. Malignant melanoma poses a diagnostic challenge as 25% may present with nonpigmented lesions. These lesions may arise from a junctional nevus and are more common in postmenopausal white women.

The measurement of tumor thickness is essential in evaluation of melanoma. A diagnosis of vulvar melanoma should be referred to a gynecologic oncologist for further evaluation and treatment. Frequently these patients require a multidisciplinary approach with other medical and surgical subspecialties consulting.

Adenocarcinoma of the vulva frequently arises within the Bartholin glands. Bartholin gland disease is typically a disease of young women. Any abscess or lesion in the bartholin gland in women older than 50 years should raise awareness of the possibility of malignancy. Providers should have a low threshold for biopsy of any Bartholin lesion in older women and for any Bartholin gland lesion or cyst that returns or persists after initial drainage.

Staging pearls

Vulvar cancer spreads by direct extension, lymphatic embolization and hematogenous spread. Lymphatic spread can occur early in the disease and portends a much worse prognosis. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system. The most significant change was in stage III disease, which now includes any patient with lymph node involvement. This change emphasizes lymph node status as the single most important prognostic factor. The 5-year overall survival of patients with locally advanced tumors but negative regional lymph nodes (62%) has been found to be significantly better than those with positive nodal status (39%, P value less than.0001) (Gynecol Oncol. 2008;110[1]:83-6.).

In patients with stage IA disease, which includes lesions less than 2 cm in size with stromal invasion of less than 1 mm, the risk of lymph node metastasis is low. These patients do not require inguinal lymph node dissection. If lesions are greater than 2 cm and/or have greater than 1 mm depth of invasion, a lymph node dissection is indicated. Lymph node dissection is performed on the ipsilateral side of the lesion as long as the lesion is more than 2 cm from a midline structure. If the lesion is in the midline or within 2 cm of the midline, a bilateral inguinal lymph node dissection is recommended.

There has been a recent uptake of the sentinel inguinal lymph node biopsy technique after two large prospective studies (the GROINSS V trial and GOG 173) validated this methodology (Lancet Oncol. 2010 Jul;11[7]:646-52 and Gynecol Oncol. 2013 Feb;128[2]:155-9).

Treatment

Surgical management of stage I and II disease involves a wide radical excision of the tumor with a 1-cm circumferential margin. Tumors with a depth of invasion of less than 1 mm do not require lymphadenectomy (Gynecol Oncol. 1992 Mar;44[3]:240-4). Stage I/II disease with deeper than 1-mm invasion requires a 2-cm margin and either sentinel node evaluation or lymphadenectomy. Survival for women with adequate resection of primary squamous carcinoma with negative lymph node involvement is greater than 90%.

Patients with metastasis to the groin frequently receive bilateral groin and pelvic radiation; however, recommendations are individualized based on size and number of metastasis. Patients should expect to receive recommendations for therapy after pathologic review and multidisciplinary consultation; therapy should be individualized for each clinical situation.

This disease is one of the elderly, but it is important to remember that treatment recommendations should not be made according to age alone. A British study found that when women over the age of 80 received standard treatment, their recurrence rate was 25% compared with a 53% recurrence rate in those whose treatment was modified (Int J Gynecol Cancer. 2009;19[4]:752-5.). In patients with advanced disease, preoperative radiation, with or without chemotherapy, is frequently regarded as the treatment of choice and may eliminate the need for radical surgery.

While vulvar cancer is a rare gynecologic malignancy, it can be devastating for patients and families, especially at late stages. Early diagnosis and treatment is imperative for improved patient outcomes. An increased awareness among patients and physicians alike may allow for earlier diagnosis and treatment.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures.

Vulvar cancer is a rare gynecologic cancer comprising only 5% of gynecologic malignancies. Given the low incidence of disease, many primary providers and even obstetricians and gynecologists many never encounter a case. Increased awareness of vulvar cancer and vulvar dysplasia among patients and physicians may decrease diagnostic delays and expedite patient therapy.

Diagnosis

There is a well documented delay in diagnosis of vulvar cancer that is attributed to both the patient and the physician. Patients may feel uncomfortable or embarrassed telling their physicians about vulvar symptoms and providers may not recognize the risk for malignancy and provide alternative therapies prior to biopsy (J Reprod Med. 1999;44[9]:766-8.).

Risk factors for vulvar cancer include human papillomavirus (HPV) infection, a history of smoking, immunosuppression, and a history of an abnormal pap smear. Vulvar dystrophy, lichen sclerosis, and squamous intraepithelial lesions have also been suggested as precursor lesions of invasive cancers. The key to early diagnosis and treatment is immediate in-office biopsy.

When evaluating a patient with a vulvar lesion, the initial evaluation should include a thorough exam with a measurement of the lesion and evaluation of inguinal lymph nodes. Also, a detailed description of a lesion’s relationship to the midline (how many centimeters away) and other vital structures (clitoris, urethra, anus) is important.

An in-office biopsy can be done on initial presentation and should include the lesion in question and underlying stroma in an effort to delineate depth of invasion. While shave biopsies may be appropriate for some skin lesions, if there is any concern for malignancy, a punch biopsy is preferred.

Pathology

Squamous cell carcinoma is the most common histologic subtype (greater than 90%) followed by malignant melanoma. Malignant melanoma poses a diagnostic challenge as 25% may present with nonpigmented lesions. These lesions may arise from a junctional nevus and are more common in postmenopausal white women.

The measurement of tumor thickness is essential in evaluation of melanoma. A diagnosis of vulvar melanoma should be referred to a gynecologic oncologist for further evaluation and treatment. Frequently these patients require a multidisciplinary approach with other medical and surgical subspecialties consulting.

Adenocarcinoma of the vulva frequently arises within the Bartholin glands. Bartholin gland disease is typically a disease of young women. Any abscess or lesion in the bartholin gland in women older than 50 years should raise awareness of the possibility of malignancy. Providers should have a low threshold for biopsy of any Bartholin lesion in older women and for any Bartholin gland lesion or cyst that returns or persists after initial drainage.

Staging pearls

Vulvar cancer spreads by direct extension, lymphatic embolization and hematogenous spread. Lymphatic spread can occur early in the disease and portends a much worse prognosis. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system. The most significant change was in stage III disease, which now includes any patient with lymph node involvement. This change emphasizes lymph node status as the single most important prognostic factor. The 5-year overall survival of patients with locally advanced tumors but negative regional lymph nodes (62%) has been found to be significantly better than those with positive nodal status (39%, P value less than.0001) (Gynecol Oncol. 2008;110[1]:83-6.).

In patients with stage IA disease, which includes lesions less than 2 cm in size with stromal invasion of less than 1 mm, the risk of lymph node metastasis is low. These patients do not require inguinal lymph node dissection. If lesions are greater than 2 cm and/or have greater than 1 mm depth of invasion, a lymph node dissection is indicated. Lymph node dissection is performed on the ipsilateral side of the lesion as long as the lesion is more than 2 cm from a midline structure. If the lesion is in the midline or within 2 cm of the midline, a bilateral inguinal lymph node dissection is recommended.

There has been a recent uptake of the sentinel inguinal lymph node biopsy technique after two large prospective studies (the GROINSS V trial and GOG 173) validated this methodology (Lancet Oncol. 2010 Jul;11[7]:646-52 and Gynecol Oncol. 2013 Feb;128[2]:155-9).

Treatment

Surgical management of stage I and II disease involves a wide radical excision of the tumor with a 1-cm circumferential margin. Tumors with a depth of invasion of less than 1 mm do not require lymphadenectomy (Gynecol Oncol. 1992 Mar;44[3]:240-4). Stage I/II disease with deeper than 1-mm invasion requires a 2-cm margin and either sentinel node evaluation or lymphadenectomy. Survival for women with adequate resection of primary squamous carcinoma with negative lymph node involvement is greater than 90%.

Patients with metastasis to the groin frequently receive bilateral groin and pelvic radiation; however, recommendations are individualized based on size and number of metastasis. Patients should expect to receive recommendations for therapy after pathologic review and multidisciplinary consultation; therapy should be individualized for each clinical situation.

This disease is one of the elderly, but it is important to remember that treatment recommendations should not be made according to age alone. A British study found that when women over the age of 80 received standard treatment, their recurrence rate was 25% compared with a 53% recurrence rate in those whose treatment was modified (Int J Gynecol Cancer. 2009;19[4]:752-5.). In patients with advanced disease, preoperative radiation, with or without chemotherapy, is frequently regarded as the treatment of choice and may eliminate the need for radical surgery.

While vulvar cancer is a rare gynecologic malignancy, it can be devastating for patients and families, especially at late stages. Early diagnosis and treatment is imperative for improved patient outcomes. An increased awareness among patients and physicians alike may allow for earlier diagnosis and treatment.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures.

Negative pressure wound therapy is a wound management system for chronic open subcutaneous or intra-abdominal wounds. Some popular commercial systems include V.A.C. therapy (KCI, San Antonio) and the Chariker-Jeter wound-sealing kit (Smith and Nephew, London). Within ob.gyn. and gynecologic oncology, they have use in the management of postoperative superficial wound dehiscence from routine surgery and in the management of the open abdomen.

The primary benefit of negative pressure wound therapy (NPWT) is the acceleration of wound healing. Postoperative superficial wound dehiscence can occur as a result of surgical factors such as wound infection and subcutaneous seroma/hematoma or systematic factors such as poor nutrition and wound ischemia.

Acceleration of wound healing results from the design of the NPWT systems. They consist of semipermeable dressings (foam), sealed with an adhesive sheet that is connected to a portable pump. By the application of –50 to –175 mm Hg of continuous or intermittent suction, the edges of the wound are drawn together, and this deforming process promotes tissue remodeling at the cellular level. Other potential benefits of negative pressure are increased blood flow, a decrease in mediators of inflammation, and an increase in collagen organization via changes in wound biochemistry.

An alternative to NPWT would be traditional gauze dressings, which can also be applied in the case of superficial wound dehiscence. These are changed up to three times a day, however, and this can result in significant patient discomfort, caregiver difficulties, and prolonged healing of weeks to months. In contrast, NPWT dressings are changed once every 2-3 days. They are also versatile and can be fit to traditionally shaped abdominal wounds, as well as difficult to dress vulvar and groin wounds (J. Obstet. Gynaecol. Can. 2011;33:1031-7).

In a series of 27 gynecologic oncology patients in whom NPWT was employed after primary wound–healing failure, there was a 96% reduction in the size of the wounds with a median number of therapy days of 32 (range, 3-88). The majority of these patients were also managed as outpatients without complication (Gynecol. Oncol. 2004;92:586-91).

There are some contraindications to NPWT that should be considered. The major, and perhaps most common, is an ongoing wound infection.

A wound that needs to be evaluated at least daily to assess the response to antibiotic therapy or need for debridement should not be managed with NPWT until the wound is deemed stable. There should be no devitalized tissue present in the wound upon application of the NPWT. If any necrotic tissue is present, then wound debridement is warranted until only well-vascularized tissue remains.

Another contraindication is the presence of malignant tissue in the wound. Negative pressure can promote this tissue growth and lead to chronic nonhealing. Other considerations would include adhesive allergies and fragile skin due to chronic steroid use or collagen vascular disorders, as NPWT can lead to skin necrosis.

Finally, the involvement of vital organs, such as exposed bowel, is a contraindication to the NPWT systems, as constant suction can promote fistula formation or hemorrhage. However, in the setting of an open abdomen after trauma surgery, there has been the development of intra-abdominal wound management systems that may be appropriate.

Although rare in obstetrics, gynecology, and gynecologic oncology, delayed abdominal closure may be necessary. This can occur after reoperation for bowel injury, in cases where bowel wall edema and increased intra-abdominal pressure preclude closure, or in cases of massive hemorrhage (for example, ruptured ectopic pregnancy) where patient instability necessitates rapid termination of the surgical case. These wounds can be managed with temporary abdominal closure techniques such as retention sutures, a Bogota bag, or loose packing (World. J. Surg. 2015; 39: 912-25).

The negative pressure systems developed for these instances are the V.A.C. abdominal dressing (KCI), Renasys NPWT (Smith and Nephew), and ABThera open abdomen negative pressure therapy (KCI). They consist of a perforated plastic sheet with foam attachments that is placed directly in the abdomen to cover the intestine. This is then covered with an adhesive dressing that is cut to accommodate the suction attachment for the negative pressure pump. This setup is easily applied and taken down, and therefore facilitates frequent abdominal washouts until true facial closure can be achieved.

There are many benefits to NPWT for the management of superficial and deep wound dehiscence in the ob.gyn. or gynecologic oncology patient. NPWT should be considered primarily with any surgical wound healing by secondary intention.

Dr. Doll is a third-year fellow in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. The authors reported having no relevant financial disclosures.

Negative pressure wound therapy is a wound management system for chronic open subcutaneous or intra-abdominal wounds. Some popular commercial systems include V.A.C. therapy (KCI, San Antonio) and the Chariker-Jeter wound-sealing kit (Smith and Nephew, London). Within ob.gyn. and gynecologic oncology, they have use in the management of postoperative superficial wound dehiscence from routine surgery and in the management of the open abdomen.

The primary benefit of negative pressure wound therapy (NPWT) is the acceleration of wound healing. Postoperative superficial wound dehiscence can occur as a result of surgical factors such as wound infection and subcutaneous seroma/hematoma or systematic factors such as poor nutrition and wound ischemia.

Acceleration of wound healing results from the design of the NPWT systems. They consist of semipermeable dressings (foam), sealed with an adhesive sheet that is connected to a portable pump. By the application of –50 to –175 mm Hg of continuous or intermittent suction, the edges of the wound are drawn together, and this deforming process promotes tissue remodeling at the cellular level. Other potential benefits of negative pressure are increased blood flow, a decrease in mediators of inflammation, and an increase in collagen organization via changes in wound biochemistry.

An alternative to NPWT would be traditional gauze dressings, which can also be applied in the case of superficial wound dehiscence. These are changed up to three times a day, however, and this can result in significant patient discomfort, caregiver difficulties, and prolonged healing of weeks to months. In contrast, NPWT dressings are changed once every 2-3 days. They are also versatile and can be fit to traditionally shaped abdominal wounds, as well as difficult to dress vulvar and groin wounds (J. Obstet. Gynaecol. Can. 2011;33:1031-7).

In a series of 27 gynecologic oncology patients in whom NPWT was employed after primary wound–healing failure, there was a 96% reduction in the size of the wounds with a median number of therapy days of 32 (range, 3-88). The majority of these patients were also managed as outpatients without complication (Gynecol. Oncol. 2004;92:586-91).

There are some contraindications to NPWT that should be considered. The major, and perhaps most common, is an ongoing wound infection.

A wound that needs to be evaluated at least daily to assess the response to antibiotic therapy or need for debridement should not be managed with NPWT until the wound is deemed stable. There should be no devitalized tissue present in the wound upon application of the NPWT. If any necrotic tissue is present, then wound debridement is warranted until only well-vascularized tissue remains.

Another contraindication is the presence of malignant tissue in the wound. Negative pressure can promote this tissue growth and lead to chronic nonhealing. Other considerations would include adhesive allergies and fragile skin due to chronic steroid use or collagen vascular disorders, as NPWT can lead to skin necrosis.

Finally, the involvement of vital organs, such as exposed bowel, is a contraindication to the NPWT systems, as constant suction can promote fistula formation or hemorrhage. However, in the setting of an open abdomen after trauma surgery, there has been the development of intra-abdominal wound management systems that may be appropriate.

Although rare in obstetrics, gynecology, and gynecologic oncology, delayed abdominal closure may be necessary. This can occur after reoperation for bowel injury, in cases where bowel wall edema and increased intra-abdominal pressure preclude closure, or in cases of massive hemorrhage (for example, ruptured ectopic pregnancy) where patient instability necessitates rapid termination of the surgical case. These wounds can be managed with temporary abdominal closure techniques such as retention sutures, a Bogota bag, or loose packing (World. J. Surg. 2015; 39: 912-25).

The negative pressure systems developed for these instances are the V.A.C. abdominal dressing (KCI), Renasys NPWT (Smith and Nephew), and ABThera open abdomen negative pressure therapy (KCI). They consist of a perforated plastic sheet with foam attachments that is placed directly in the abdomen to cover the intestine. This is then covered with an adhesive dressing that is cut to accommodate the suction attachment for the negative pressure pump. This setup is easily applied and taken down, and therefore facilitates frequent abdominal washouts until true facial closure can be achieved.

There are many benefits to NPWT for the management of superficial and deep wound dehiscence in the ob.gyn. or gynecologic oncology patient. NPWT should be considered primarily with any surgical wound healing by secondary intention.

Dr. Doll is a third-year fellow in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. The authors reported having no relevant financial disclosures.

Negative pressure wound therapy is a wound management system for chronic open subcutaneous or intra-abdominal wounds. Some popular commercial systems include V.A.C. therapy (KCI, San Antonio) and the Chariker-Jeter wound-sealing kit (Smith and Nephew, London). Within ob.gyn. and gynecologic oncology, they have use in the management of postoperative superficial wound dehiscence from routine surgery and in the management of the open abdomen.

The primary benefit of negative pressure wound therapy (NPWT) is the acceleration of wound healing. Postoperative superficial wound dehiscence can occur as a result of surgical factors such as wound infection and subcutaneous seroma/hematoma or systematic factors such as poor nutrition and wound ischemia.

Acceleration of wound healing results from the design of the NPWT systems. They consist of semipermeable dressings (foam), sealed with an adhesive sheet that is connected to a portable pump. By the application of –50 to –175 mm Hg of continuous or intermittent suction, the edges of the wound are drawn together, and this deforming process promotes tissue remodeling at the cellular level. Other potential benefits of negative pressure are increased blood flow, a decrease in mediators of inflammation, and an increase in collagen organization via changes in wound biochemistry.

An alternative to NPWT would be traditional gauze dressings, which can also be applied in the case of superficial wound dehiscence. These are changed up to three times a day, however, and this can result in significant patient discomfort, caregiver difficulties, and prolonged healing of weeks to months. In contrast, NPWT dressings are changed once every 2-3 days. They are also versatile and can be fit to traditionally shaped abdominal wounds, as well as difficult to dress vulvar and groin wounds (J. Obstet. Gynaecol. Can. 2011;33:1031-7).

In a series of 27 gynecologic oncology patients in whom NPWT was employed after primary wound–healing failure, there was a 96% reduction in the size of the wounds with a median number of therapy days of 32 (range, 3-88). The majority of these patients were also managed as outpatients without complication (Gynecol. Oncol. 2004;92:586-91).

There are some contraindications to NPWT that should be considered. The major, and perhaps most common, is an ongoing wound infection.

A wound that needs to be evaluated at least daily to assess the response to antibiotic therapy or need for debridement should not be managed with NPWT until the wound is deemed stable. There should be no devitalized tissue present in the wound upon application of the NPWT. If any necrotic tissue is present, then wound debridement is warranted until only well-vascularized tissue remains.

Another contraindication is the presence of malignant tissue in the wound. Negative pressure can promote this tissue growth and lead to chronic nonhealing. Other considerations would include adhesive allergies and fragile skin due to chronic steroid use or collagen vascular disorders, as NPWT can lead to skin necrosis.

Finally, the involvement of vital organs, such as exposed bowel, is a contraindication to the NPWT systems, as constant suction can promote fistula formation or hemorrhage. However, in the setting of an open abdomen after trauma surgery, there has been the development of intra-abdominal wound management systems that may be appropriate.

Although rare in obstetrics, gynecology, and gynecologic oncology, delayed abdominal closure may be necessary. This can occur after reoperation for bowel injury, in cases where bowel wall edema and increased intra-abdominal pressure preclude closure, or in cases of massive hemorrhage (for example, ruptured ectopic pregnancy) where patient instability necessitates rapid termination of the surgical case. These wounds can be managed with temporary abdominal closure techniques such as retention sutures, a Bogota bag, or loose packing (World. J. Surg. 2015; 39: 912-25).

The negative pressure systems developed for these instances are the V.A.C. abdominal dressing (KCI), Renasys NPWT (Smith and Nephew), and ABThera open abdomen negative pressure therapy (KCI). They consist of a perforated plastic sheet with foam attachments that is placed directly in the abdomen to cover the intestine. This is then covered with an adhesive dressing that is cut to accommodate the suction attachment for the negative pressure pump. This setup is easily applied and taken down, and therefore facilitates frequent abdominal washouts until true facial closure can be achieved.

There are many benefits to NPWT for the management of superficial and deep wound dehiscence in the ob.gyn. or gynecologic oncology patient. NPWT should be considered primarily with any surgical wound healing by secondary intention.

Dr. Doll is a third-year fellow in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. The authors reported having no relevant financial disclosures.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor in the division of gynecologic oncology at the university. Dr. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.

Obstetrician-gynecologists play a unique role in screening women for various malignancies, including breast, colon, and cervical carcinoma. Although less common, genetic syndromes also can affect the female reproductive tract; therefore, knowledge of the screening guidelines for the most common genetic syndromes – hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome, and Cowden syndrome – is important.

Hereditary breast and ovarian cancer syndrome

Caused by autosomal-dominant deletions in the BRCA1/2 genes, the lifetime risk of ovarian cancer in patients with a BRCA1 and BRCA2 mutation is 39%-46% and 12%-20%, respectively. Although not proven to improve detection or survival, the American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend that women with BRCA1/2 mutations should undergo screening with transvaginal ultrasonography and CA125 every 6 months beginning between ages 30-35 years or 5-10 years prior to the age of the youngest affected family member. For patients who have not completed childbearing, a recent meta-analysis showed that use of oral contraceptives was associated with a decreased risk of ovarian cancer in patients with BRCA1/2 (J. Clin. Oncol. 2013;31:4188-98). Once childbearing has been completed or at the age of 40 years, a risk-reducing bilateral salpingo-oophorectomy (BSO) should be strongly considered (Gynecol. Oncol. 2009;113:6-11; Obstet. Gynecol. 2011;117:742-6).

In addition, patients with BRCA 1/2 mutations carry a 65%-74% lifetime risk of developing breast cancer (Gynecol. Oncol. 2009;113:6-11).ACOG recommends that these women begin screening for breast cancer at the age of 25 years through semiannual self-breast exams as well as annual mammography and breast MRI or sooner if a family member’s cancer was diagnosed prior to this age. Chemoprevention with tamoxifen also has been shown to reduce the risk of breast cancer in patients with BRCA2 disease, but is less effective for BRCA1 patients. Prophylactic mastectomy has the ability to reduce a woman’s risk of developing breast cancer by 90%-95%.

Hereditary nonpolyposis colorectal cancer syndrome

Another autosomal-dominant disorder, hereditary nonpolyposis colorectal cancer (HNPCC) syndrome arises as a result of a genetic defect in DNA mismatch repair mechanisms. Colon cancer is the most common malignancy associated with this syndrome, with a 70% risk by the age of 70 years (JAMA 2006;296:1507-17). Other associated cancers include those of the urinary tract, hepatobiliary tract, small intestine, skin, and brain, but strong supportive data are lacking. Beginning at age 20-25 years (or 10 years before the age of the youngest family member to develop colon cancer), a colonoscopy is recommended every 1-2 years. Annual urinalysis with cytology is advocated by some as a screening test for urinary tract cancers.

Patients with HNPCC have up to a 60% lifetime risk of endometrial cancer and a 10% risk of ovarian cancer (Int. J. Cancer 1999;81:214-8; Hum. Mol. Gene. 1997;6:105-10). The American Cancer Society recommends an endometrial biopsy and transvaginal ultrasonography annually between 30-35 years of age (JAMA 2006;296:1507-17). Schmeler et al. compared outcomes among 315 women with mismatch repair defects, 61 of whom underwent risk-reducing hysterectomy and BSO. With an average follow-up of greater than 7 years, none of the patients who underwent surgery developed cancer, while 33% of those who did not have surgery developed endometrial cancer and 5.5% developed ovarian cancer (N. Engl. J. Med. 2006;354:261-9). Because of these data, risk-reducing surgery at the age of 35 should be considered.

Cowden Syndrome

Cowden Syndrome, caused by an autosomal-dominant mutation in the PTEN gene, is associated with an up to 10% lifetime risk of endometrial cancer and a 50% risk of breast cancer (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). The NCCN notes that data are limited, but discussion of endometrial cancer symptoms should be encouraged (NCCN Guidelines Version 4, 2013). Annual endometrial sampling and ultrasound should be considered in woman aged 35-40 years or 10 years earlier than the youngest affected family member (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). Screening for breast cancer should include annual mammography and breast MRI starting between age 30-35 years or earlier depending on family history, per the NCCN guidelines.

It is important to note that additional genetic syndromes can have repercussions on the female genital tract, including the Li-Fraumeni (ovarian cancer), the Peutz-Jeghers (sex cord–stromal tumors of the ovary, granulosa cell tumors), and the Ollier (granulosa cell tumors) syndromes; unfortunately, screening guidelines for these rare syndromes have not been well studied (JAMA 2006;296:1507-17).

Dr. Schuler is a gynecologic oncologist at Good Samaritan Hospital in Cincinnati. Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig and Dr. Schuler said they had no relevant financial disclosures.

Obstetrician-gynecologists play a unique role in screening women for various malignancies, including breast, colon, and cervical carcinoma. Although less common, genetic syndromes also can affect the female reproductive tract; therefore, knowledge of the screening guidelines for the most common genetic syndromes – hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome, and Cowden syndrome – is important.

Hereditary breast and ovarian cancer syndrome

Caused by autosomal-dominant deletions in the BRCA1/2 genes, the lifetime risk of ovarian cancer in patients with a BRCA1 and BRCA2 mutation is 39%-46% and 12%-20%, respectively. Although not proven to improve detection or survival, the American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend that women with BRCA1/2 mutations should undergo screening with transvaginal ultrasonography and CA125 every 6 months beginning between ages 30-35 years or 5-10 years prior to the age of the youngest affected family member. For patients who have not completed childbearing, a recent meta-analysis showed that use of oral contraceptives was associated with a decreased risk of ovarian cancer in patients with BRCA1/2 (J. Clin. Oncol. 2013;31:4188-98). Once childbearing has been completed or at the age of 40 years, a risk-reducing bilateral salpingo-oophorectomy (BSO) should be strongly considered (Gynecol. Oncol. 2009;113:6-11; Obstet. Gynecol. 2011;117:742-6).

In addition, patients with BRCA 1/2 mutations carry a 65%-74% lifetime risk of developing breast cancer (Gynecol. Oncol. 2009;113:6-11).ACOG recommends that these women begin screening for breast cancer at the age of 25 years through semiannual self-breast exams as well as annual mammography and breast MRI or sooner if a family member’s cancer was diagnosed prior to this age. Chemoprevention with tamoxifen also has been shown to reduce the risk of breast cancer in patients with BRCA2 disease, but is less effective for BRCA1 patients. Prophylactic mastectomy has the ability to reduce a woman’s risk of developing breast cancer by 90%-95%.

Hereditary nonpolyposis colorectal cancer syndrome

Another autosomal-dominant disorder, hereditary nonpolyposis colorectal cancer (HNPCC) syndrome arises as a result of a genetic defect in DNA mismatch repair mechanisms. Colon cancer is the most common malignancy associated with this syndrome, with a 70% risk by the age of 70 years (JAMA 2006;296:1507-17). Other associated cancers include those of the urinary tract, hepatobiliary tract, small intestine, skin, and brain, but strong supportive data are lacking. Beginning at age 20-25 years (or 10 years before the age of the youngest family member to develop colon cancer), a colonoscopy is recommended every 1-2 years. Annual urinalysis with cytology is advocated by some as a screening test for urinary tract cancers.

Patients with HNPCC have up to a 60% lifetime risk of endometrial cancer and a 10% risk of ovarian cancer (Int. J. Cancer 1999;81:214-8; Hum. Mol. Gene. 1997;6:105-10). The American Cancer Society recommends an endometrial biopsy and transvaginal ultrasonography annually between 30-35 years of age (JAMA 2006;296:1507-17). Schmeler et al. compared outcomes among 315 women with mismatch repair defects, 61 of whom underwent risk-reducing hysterectomy and BSO. With an average follow-up of greater than 7 years, none of the patients who underwent surgery developed cancer, while 33% of those who did not have surgery developed endometrial cancer and 5.5% developed ovarian cancer (N. Engl. J. Med. 2006;354:261-9). Because of these data, risk-reducing surgery at the age of 35 should be considered.

Cowden Syndrome

Cowden Syndrome, caused by an autosomal-dominant mutation in the PTEN gene, is associated with an up to 10% lifetime risk of endometrial cancer and a 50% risk of breast cancer (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). The NCCN notes that data are limited, but discussion of endometrial cancer symptoms should be encouraged (NCCN Guidelines Version 4, 2013). Annual endometrial sampling and ultrasound should be considered in woman aged 35-40 years or 10 years earlier than the youngest affected family member (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). Screening for breast cancer should include annual mammography and breast MRI starting between age 30-35 years or earlier depending on family history, per the NCCN guidelines.

It is important to note that additional genetic syndromes can have repercussions on the female genital tract, including the Li-Fraumeni (ovarian cancer), the Peutz-Jeghers (sex cord–stromal tumors of the ovary, granulosa cell tumors), and the Ollier (granulosa cell tumors) syndromes; unfortunately, screening guidelines for these rare syndromes have not been well studied (JAMA 2006;296:1507-17).

Dr. Schuler is a gynecologic oncologist at Good Samaritan Hospital in Cincinnati. Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig and Dr. Schuler said they had no relevant financial disclosures.

Obstetrician-gynecologists play a unique role in screening women for various malignancies, including breast, colon, and cervical carcinoma. Although less common, genetic syndromes also can affect the female reproductive tract; therefore, knowledge of the screening guidelines for the most common genetic syndromes – hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome, and Cowden syndrome – is important.

Hereditary breast and ovarian cancer syndrome

Caused by autosomal-dominant deletions in the BRCA1/2 genes, the lifetime risk of ovarian cancer in patients with a BRCA1 and BRCA2 mutation is 39%-46% and 12%-20%, respectively. Although not proven to improve detection or survival, the American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend that women with BRCA1/2 mutations should undergo screening with transvaginal ultrasonography and CA125 every 6 months beginning between ages 30-35 years or 5-10 years prior to the age of the youngest affected family member. For patients who have not completed childbearing, a recent meta-analysis showed that use of oral contraceptives was associated with a decreased risk of ovarian cancer in patients with BRCA1/2 (J. Clin. Oncol. 2013;31:4188-98). Once childbearing has been completed or at the age of 40 years, a risk-reducing bilateral salpingo-oophorectomy (BSO) should be strongly considered (Gynecol. Oncol. 2009;113:6-11; Obstet. Gynecol. 2011;117:742-6).

In addition, patients with BRCA 1/2 mutations carry a 65%-74% lifetime risk of developing breast cancer (Gynecol. Oncol. 2009;113:6-11).ACOG recommends that these women begin screening for breast cancer at the age of 25 years through semiannual self-breast exams as well as annual mammography and breast MRI or sooner if a family member’s cancer was diagnosed prior to this age. Chemoprevention with tamoxifen also has been shown to reduce the risk of breast cancer in patients with BRCA2 disease, but is less effective for BRCA1 patients. Prophylactic mastectomy has the ability to reduce a woman’s risk of developing breast cancer by 90%-95%.

Hereditary nonpolyposis colorectal cancer syndrome

Another autosomal-dominant disorder, hereditary nonpolyposis colorectal cancer (HNPCC) syndrome arises as a result of a genetic defect in DNA mismatch repair mechanisms. Colon cancer is the most common malignancy associated with this syndrome, with a 70% risk by the age of 70 years (JAMA 2006;296:1507-17). Other associated cancers include those of the urinary tract, hepatobiliary tract, small intestine, skin, and brain, but strong supportive data are lacking. Beginning at age 20-25 years (or 10 years before the age of the youngest family member to develop colon cancer), a colonoscopy is recommended every 1-2 years. Annual urinalysis with cytology is advocated by some as a screening test for urinary tract cancers.

Patients with HNPCC have up to a 60% lifetime risk of endometrial cancer and a 10% risk of ovarian cancer (Int. J. Cancer 1999;81:214-8; Hum. Mol. Gene. 1997;6:105-10). The American Cancer Society recommends an endometrial biopsy and transvaginal ultrasonography annually between 30-35 years of age (JAMA 2006;296:1507-17). Schmeler et al. compared outcomes among 315 women with mismatch repair defects, 61 of whom underwent risk-reducing hysterectomy and BSO. With an average follow-up of greater than 7 years, none of the patients who underwent surgery developed cancer, while 33% of those who did not have surgery developed endometrial cancer and 5.5% developed ovarian cancer (N. Engl. J. Med. 2006;354:261-9). Because of these data, risk-reducing surgery at the age of 35 should be considered.

Cowden Syndrome

Cowden Syndrome, caused by an autosomal-dominant mutation in the PTEN gene, is associated with an up to 10% lifetime risk of endometrial cancer and a 50% risk of breast cancer (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). The NCCN notes that data are limited, but discussion of endometrial cancer symptoms should be encouraged (NCCN Guidelines Version 4, 2013). Annual endometrial sampling and ultrasound should be considered in woman aged 35-40 years or 10 years earlier than the youngest affected family member (Obstet. Gynecol. Clin. N. Am. 2010;37:109-33). Screening for breast cancer should include annual mammography and breast MRI starting between age 30-35 years or earlier depending on family history, per the NCCN guidelines.

It is important to note that additional genetic syndromes can have repercussions on the female genital tract, including the Li-Fraumeni (ovarian cancer), the Peutz-Jeghers (sex cord–stromal tumors of the ovary, granulosa cell tumors), and the Ollier (granulosa cell tumors) syndromes; unfortunately, screening guidelines for these rare syndromes have not been well studied (JAMA 2006;296:1507-17).

Dr. Schuler is a gynecologic oncologist at Good Samaritan Hospital in Cincinnati. Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig and Dr. Schuler said they had no relevant financial disclosures.

Numerous screening methods for cervical cancer have been proposed internationally by various professional societies, including Pap cytology alone, cytology with human papillomavirus testing as triage (HPV testing for atypical squamous cells of unknown significance [ASCUS] on cytology), cytology with HPV cotesting (cytology and HPV testing obtained together), HPV testing alone, or HPV testing followed by Pap cytology triage (cytology in patients who are positive for high-risk oncogenic subtypes of HPV). Recommendations for use of cervical cytology and HPV testing continue to vary among professional societies, with variable adoption of these guidelines by providers as well. (Am. J. Prev. Med. 2013;45:175-81).

In 2012, updated cervical cancer screening recommendations were published by ASCCP (the American Society for Colposcopy and Cervical Pathology) (Am. J. Clin. Pathol. 2012;137:516-42); the USPSTF (U.S. Preventive Services Task Force ); and ACOG (the American College of Obstetricians and Gynecologists) (Obstet. Gynecol. 2009;114:1409-20).

These most recent guidelines show a greater degree of harmony across these governing bodies than did prior guidelines. All three professional societies recommend initiating screening at age 21 years and ceasing screening at age 65 years with an adequate screening history. All groups recommend against HPV cotesting in women under 30 years of age; however, after age 30 years, ASCCP and ACOG recommend HPV cotesting every 5 years as the preferred method of cervical cancer screening, while USPSTF suggests this only as an "option." Primary HPV testing without concurrent cytology for cervical cancer screening is not currently recommended by ASCCP and USPSTF and is not addressed by ACOG.

Efficacy of screening modalities

The rationale behind these screening recommendations depends on the efficacy of both cervical cytology and HPV testing to identify preinvasive cases or invasive cervical cancer. Multiple studies have addressed the sensitivity and specificity of cytology in cervical cancer screening. Overall, the sensitivity of Pap cytology is low at approximately 51%, while specificity is high at 96%-98% (Ann. Intern. Med. 2000;132:810-9; Vaccine 2008;26 Suppl. 10:K29-41). Since the initiation of cervical cytology for cancer screening, serial annual screening has compensated for the overall poor sensitivity of the test. Two consecutive annual Pap tests can increase overall sensitivity for detection of cervical cancer to 76%, and three consecutive annual Pap tests can increase overall sensitivity to 88%.

Unlike Pap cytology, HPV testing has a high sensitivity, ranging from 81%-97% in detection of cervical cancer (N. Engl. J. Med. 2007;357:1579-88). As a result, HPV testing does not rely on serial testing for accuracy and has a high negative predictive value, making negative results very reassuring. However, HPV testing has a slightly lower specificity of 94%, which results in a higher number of false positives. Furthermore, many patients who screen positive for high-risk HPV subtypes may have transient HPV infections, which are not clinically significant, and may not cause invasive cervical cancer.

Several randomized studies have compared Pap cytology to HPV testing for use in cervical cancer screening. A Canadian study randomized more than 10,000 women to either Pap cytology or HPV testing to detect cervical intraepithelial neoplasia (CIN) 2 or higher grade cervical lesions (Int. J. Cancer. 2006;119:615-23). Findings showed a sensitivity of 55.4% for Pap cytology vs. 94.6% for HPV testing. Pap cytology had a specificity of 96.8% while HPV testing had a specificity of 94.1%. The negative predictive value of HPV testing was 100%.

Swedescreen, a Swedish study of more 12,000 women (J. Med. Virol. 2007;79:1169-75), and POBASCAM, a large Dutch study of more than 18,000 women (Lancet 2007;370:1764-72), both compared HPV testing combined with Pap cytology (cotesting) to cytology alone. Both studies found that patients screened with Pap cytology alone had more CIN2 or greater lesions in follow-up than did patients screened with cytology in combination with HPV testing (relative risk, 0.53-0.58 for CIN 2+ and RR 0.45-0.53 for CIN 3+) (J. Natl. Cancer Inst. 2009;101:88-99).

Because of the higher sensitivity of HPV testing compared with Pap cytology, some have advocated the use of HPV testing as primary screening with cytology triage rather than the reverse (cytology with HPV triage), which is more commonly used today. A Finnish study showed that primary HPV testing with cytology performed only in patients who screened positive for high risk oncogenic subtypes of HPV was more sensitive than was conventional cytology in identifying cervical dysplasia and cancer. Additionally, in women over age 35 years, HPV testing combined with Pap cytology triage was more specific than cytology alone, and decreased colposcopy referrals and follow-up tests, making this screening option cost effective (J. Natl. Cancer Inst. 2009;101:1612-23). Nowhere else in medicine is a more specific test used prior to a more sensitive test when screening for disease; the screening test is typically the more sensitive, while the confirmatory test is the more specific.

HPV vaccination and effects on screening

Currently, given that the HPV vaccines available do not protect women from all oncogenic HPV types, the ASCCP, USPSTF, and ACOG all recommend screening vaccinated women in an identical fashion to unvaccinated women. Increasing vaccination rates will likely have an impact on the efficacy of the various cervical cancer screening modalities. Vaccination will result in a reduction in the prevalence of cytologic abnormalities. As disease prevalence decreases and screening intervals increase based on current guidelines, the positive predictive value of Pap cytology also will decline, resulting in more false-positive diagnoses and possibly unnecessary procedures and patient stress (Vaccine 2013;31:5495-9). As prevalence of disease decreases, Pap cytology has the potential to become less reliable. While the positive predictive value of HPV testing also declines with decreasing disease prevalence, HPV testing is more reproducible than interpretation of Pap cytology, so the extent of increasing false-positive results may be less (Vaccine 2006;24 Suppl 3:S3/171-7).

Future directions

HPV testing as primary screening for cervical cancer is not currently recommended. However, in the post-HPV vaccination era, this may become an increasingly reasonable approach, particularly in conjunction with Pap cytology used to triage patients who test positive for high-risk HPV subtypes. HPV testing has much greater sensitivity than Pap cytology does and can better identify patients who are likely to have a cytologic abnormality. In this group of patients with greater disease prevalence, the slightly higher specificity of Pap cytology can then be used to identify precancerous lesions and guide treatment. Once this group of patients with higher lesion prevalence than the general population has been identified through HPV testing, Pap cytology can then be used and will perform better than in a lower prevalence population.

The importance of Pap cytology and HPV testing in cervical cancer screening continues to evolve, particularly in the current era of HPV vaccination. The combination of HPV testing followed by Pap cytology has potential for becoming a highly effective screening strategy; however, the optimal administration of these tests is yet to be determined. As current screening modalities improve and new technologies emerge, ongoing work is needed to identify the most effective screening method for cervical cancer.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Kim is the department of gynecologic oncology at UNC-Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at UNC-Chapel Hill.

Numerous screening methods for cervical cancer have been proposed internationally by various professional societies, including Pap cytology alone, cytology with human papillomavirus testing as triage (HPV testing for atypical squamous cells of unknown significance [ASCUS] on cytology), cytology with HPV cotesting (cytology and HPV testing obtained together), HPV testing alone, or HPV testing followed by Pap cytology triage (cytology in patients who are positive for high-risk oncogenic subtypes of HPV). Recommendations for use of cervical cytology and HPV testing continue to vary among professional societies, with variable adoption of these guidelines by providers as well. (Am. J. Prev. Med. 2013;45:175-81).

In 2012, updated cervical cancer screening recommendations were published by ASCCP (the American Society for Colposcopy and Cervical Pathology) (Am. J. Clin. Pathol. 2012;137:516-42); the USPSTF (U.S. Preventive Services Task Force ); and ACOG (the American College of Obstetricians and Gynecologists) (Obstet. Gynecol. 2009;114:1409-20).

These most recent guidelines show a greater degree of harmony across these governing bodies than did prior guidelines. All three professional societies recommend initiating screening at age 21 years and ceasing screening at age 65 years with an adequate screening history. All groups recommend against HPV cotesting in women under 30 years of age; however, after age 30 years, ASCCP and ACOG recommend HPV cotesting every 5 years as the preferred method of cervical cancer screening, while USPSTF suggests this only as an "option." Primary HPV testing without concurrent cytology for cervical cancer screening is not currently recommended by ASCCP and USPSTF and is not addressed by ACOG.

Efficacy of screening modalities

The rationale behind these screening recommendations depends on the efficacy of both cervical cytology and HPV testing to identify preinvasive cases or invasive cervical cancer. Multiple studies have addressed the sensitivity and specificity of cytology in cervical cancer screening. Overall, the sensitivity of Pap cytology is low at approximately 51%, while specificity is high at 96%-98% (Ann. Intern. Med. 2000;132:810-9; Vaccine 2008;26 Suppl. 10:K29-41). Since the initiation of cervical cytology for cancer screening, serial annual screening has compensated for the overall poor sensitivity of the test. Two consecutive annual Pap tests can increase overall sensitivity for detection of cervical cancer to 76%, and three consecutive annual Pap tests can increase overall sensitivity to 88%.

Unlike Pap cytology, HPV testing has a high sensitivity, ranging from 81%-97% in detection of cervical cancer (N. Engl. J. Med. 2007;357:1579-88). As a result, HPV testing does not rely on serial testing for accuracy and has a high negative predictive value, making negative results very reassuring. However, HPV testing has a slightly lower specificity of 94%, which results in a higher number of false positives. Furthermore, many patients who screen positive for high-risk HPV subtypes may have transient HPV infections, which are not clinically significant, and may not cause invasive cervical cancer.

Several randomized studies have compared Pap cytology to HPV testing for use in cervical cancer screening. A Canadian study randomized more than 10,000 women to either Pap cytology or HPV testing to detect cervical intraepithelial neoplasia (CIN) 2 or higher grade cervical lesions (Int. J. Cancer. 2006;119:615-23). Findings showed a sensitivity of 55.4% for Pap cytology vs. 94.6% for HPV testing. Pap cytology had a specificity of 96.8% while HPV testing had a specificity of 94.1%. The negative predictive value of HPV testing was 100%.

Swedescreen, a Swedish study of more 12,000 women (J. Med. Virol. 2007;79:1169-75), and POBASCAM, a large Dutch study of more than 18,000 women (Lancet 2007;370:1764-72), both compared HPV testing combined with Pap cytology (cotesting) to cytology alone. Both studies found that patients screened with Pap cytology alone had more CIN2 or greater lesions in follow-up than did patients screened with cytology in combination with HPV testing (relative risk, 0.53-0.58 for CIN 2+ and RR 0.45-0.53 for CIN 3+) (J. Natl. Cancer Inst. 2009;101:88-99).

Because of the higher sensitivity of HPV testing compared with Pap cytology, some have advocated the use of HPV testing as primary screening with cytology triage rather than the reverse (cytology with HPV triage), which is more commonly used today. A Finnish study showed that primary HPV testing with cytology performed only in patients who screened positive for high risk oncogenic subtypes of HPV was more sensitive than was conventional cytology in identifying cervical dysplasia and cancer. Additionally, in women over age 35 years, HPV testing combined with Pap cytology triage was more specific than cytology alone, and decreased colposcopy referrals and follow-up tests, making this screening option cost effective (J. Natl. Cancer Inst. 2009;101:1612-23). Nowhere else in medicine is a more specific test used prior to a more sensitive test when screening for disease; the screening test is typically the more sensitive, while the confirmatory test is the more specific.

HPV vaccination and effects on screening

Currently, given that the HPV vaccines available do not protect women from all oncogenic HPV types, the ASCCP, USPSTF, and ACOG all recommend screening vaccinated women in an identical fashion to unvaccinated women. Increasing vaccination rates will likely have an impact on the efficacy of the various cervical cancer screening modalities. Vaccination will result in a reduction in the prevalence of cytologic abnormalities. As disease prevalence decreases and screening intervals increase based on current guidelines, the positive predictive value of Pap cytology also will decline, resulting in more false-positive diagnoses and possibly unnecessary procedures and patient stress (Vaccine 2013;31:5495-9). As prevalence of disease decreases, Pap cytology has the potential to become less reliable. While the positive predictive value of HPV testing also declines with decreasing disease prevalence, HPV testing is more reproducible than interpretation of Pap cytology, so the extent of increasing false-positive results may be less (Vaccine 2006;24 Suppl 3:S3/171-7).

Future directions

HPV testing as primary screening for cervical cancer is not currently recommended. However, in the post-HPV vaccination era, this may become an increasingly reasonable approach, particularly in conjunction with Pap cytology used to triage patients who test positive for high-risk HPV subtypes. HPV testing has much greater sensitivity than Pap cytology does and can better identify patients who are likely to have a cytologic abnormality. In this group of patients with greater disease prevalence, the slightly higher specificity of Pap cytology can then be used to identify precancerous lesions and guide treatment. Once this group of patients with higher lesion prevalence than the general population has been identified through HPV testing, Pap cytology can then be used and will perform better than in a lower prevalence population.

The importance of Pap cytology and HPV testing in cervical cancer screening continues to evolve, particularly in the current era of HPV vaccination. The combination of HPV testing followed by Pap cytology has potential for becoming a highly effective screening strategy; however, the optimal administration of these tests is yet to be determined. As current screening modalities improve and new technologies emerge, ongoing work is needed to identify the most effective screening method for cervical cancer.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Kim is the department of gynecologic oncology at UNC-Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at UNC-Chapel Hill.

Numerous screening methods for cervical cancer have been proposed internationally by various professional societies, including Pap cytology alone, cytology with human papillomavirus testing as triage (HPV testing for atypical squamous cells of unknown significance [ASCUS] on cytology), cytology with HPV cotesting (cytology and HPV testing obtained together), HPV testing alone, or HPV testing followed by Pap cytology triage (cytology in patients who are positive for high-risk oncogenic subtypes of HPV). Recommendations for use of cervical cytology and HPV testing continue to vary among professional societies, with variable adoption of these guidelines by providers as well. (Am. J. Prev. Med. 2013;45:175-81).

In 2012, updated cervical cancer screening recommendations were published by ASCCP (the American Society for Colposcopy and Cervical Pathology) (Am. J. Clin. Pathol. 2012;137:516-42); the USPSTF (U.S. Preventive Services Task Force ); and ACOG (the American College of Obstetricians and Gynecologists) (Obstet. Gynecol. 2009;114:1409-20).

These most recent guidelines show a greater degree of harmony across these governing bodies than did prior guidelines. All three professional societies recommend initiating screening at age 21 years and ceasing screening at age 65 years with an adequate screening history. All groups recommend against HPV cotesting in women under 30 years of age; however, after age 30 years, ASCCP and ACOG recommend HPV cotesting every 5 years as the preferred method of cervical cancer screening, while USPSTF suggests this only as an "option." Primary HPV testing without concurrent cytology for cervical cancer screening is not currently recommended by ASCCP and USPSTF and is not addressed by ACOG.

Efficacy of screening modalities

The rationale behind these screening recommendations depends on the efficacy of both cervical cytology and HPV testing to identify preinvasive cases or invasive cervical cancer. Multiple studies have addressed the sensitivity and specificity of cytology in cervical cancer screening. Overall, the sensitivity of Pap cytology is low at approximately 51%, while specificity is high at 96%-98% (Ann. Intern. Med. 2000;132:810-9; Vaccine 2008;26 Suppl. 10:K29-41). Since the initiation of cervical cytology for cancer screening, serial annual screening has compensated for the overall poor sensitivity of the test. Two consecutive annual Pap tests can increase overall sensitivity for detection of cervical cancer to 76%, and three consecutive annual Pap tests can increase overall sensitivity to 88%.

Unlike Pap cytology, HPV testing has a high sensitivity, ranging from 81%-97% in detection of cervical cancer (N. Engl. J. Med. 2007;357:1579-88). As a result, HPV testing does not rely on serial testing for accuracy and has a high negative predictive value, making negative results very reassuring. However, HPV testing has a slightly lower specificity of 94%, which results in a higher number of false positives. Furthermore, many patients who screen positive for high-risk HPV subtypes may have transient HPV infections, which are not clinically significant, and may not cause invasive cervical cancer.

Several randomized studies have compared Pap cytology to HPV testing for use in cervical cancer screening. A Canadian study randomized more than 10,000 women to either Pap cytology or HPV testing to detect cervical intraepithelial neoplasia (CIN) 2 or higher grade cervical lesions (Int. J. Cancer. 2006;119:615-23). Findings showed a sensitivity of 55.4% for Pap cytology vs. 94.6% for HPV testing. Pap cytology had a specificity of 96.8% while HPV testing had a specificity of 94.1%. The negative predictive value of HPV testing was 100%.

Swedescreen, a Swedish study of more 12,000 women (J. Med. Virol. 2007;79:1169-75), and POBASCAM, a large Dutch study of more than 18,000 women (Lancet 2007;370:1764-72), both compared HPV testing combined with Pap cytology (cotesting) to cytology alone. Both studies found that patients screened with Pap cytology alone had more CIN2 or greater lesions in follow-up than did patients screened with cytology in combination with HPV testing (relative risk, 0.53-0.58 for CIN 2+ and RR 0.45-0.53 for CIN 3+) (J. Natl. Cancer Inst. 2009;101:88-99).

Because of the higher sensitivity of HPV testing compared with Pap cytology, some have advocated the use of HPV testing as primary screening with cytology triage rather than the reverse (cytology with HPV triage), which is more commonly used today. A Finnish study showed that primary HPV testing with cytology performed only in patients who screened positive for high risk oncogenic subtypes of HPV was more sensitive than was conventional cytology in identifying cervical dysplasia and cancer. Additionally, in women over age 35 years, HPV testing combined with Pap cytology triage was more specific than cytology alone, and decreased colposcopy referrals and follow-up tests, making this screening option cost effective (J. Natl. Cancer Inst. 2009;101:1612-23). Nowhere else in medicine is a more specific test used prior to a more sensitive test when screening for disease; the screening test is typically the more sensitive, while the confirmatory test is the more specific.

HPV vaccination and effects on screening

Currently, given that the HPV vaccines available do not protect women from all oncogenic HPV types, the ASCCP, USPSTF, and ACOG all recommend screening vaccinated women in an identical fashion to unvaccinated women. Increasing vaccination rates will likely have an impact on the efficacy of the various cervical cancer screening modalities. Vaccination will result in a reduction in the prevalence of cytologic abnormalities. As disease prevalence decreases and screening intervals increase based on current guidelines, the positive predictive value of Pap cytology also will decline, resulting in more false-positive diagnoses and possibly unnecessary procedures and patient stress (Vaccine 2013;31:5495-9). As prevalence of disease decreases, Pap cytology has the potential to become less reliable. While the positive predictive value of HPV testing also declines with decreasing disease prevalence, HPV testing is more reproducible than interpretation of Pap cytology, so the extent of increasing false-positive results may be less (Vaccine 2006;24 Suppl 3:S3/171-7).

Future directions

HPV testing as primary screening for cervical cancer is not currently recommended. However, in the post-HPV vaccination era, this may become an increasingly reasonable approach, particularly in conjunction with Pap cytology used to triage patients who test positive for high-risk HPV subtypes. HPV testing has much greater sensitivity than Pap cytology does and can better identify patients who are likely to have a cytologic abnormality. In this group of patients with greater disease prevalence, the slightly higher specificity of Pap cytology can then be used to identify precancerous lesions and guide treatment. Once this group of patients with higher lesion prevalence than the general population has been identified through HPV testing, Pap cytology can then be used and will perform better than in a lower prevalence population.

The importance of Pap cytology and HPV testing in cervical cancer screening continues to evolve, particularly in the current era of HPV vaccination. The combination of HPV testing followed by Pap cytology has potential for becoming a highly effective screening strategy; however, the optimal administration of these tests is yet to be determined. As current screening modalities improve and new technologies emerge, ongoing work is needed to identify the most effective screening method for cervical cancer.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Kim is the department of gynecologic oncology at UNC-Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at UNC-Chapel Hill.