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Can transvaginal ultrasound detect endometrial disease among asymptomatic postmenopausal patients?
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women (strength of recommendation: B, based on cohort studies).
Evidence summary
In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound.1 Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population.
An additional study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound.2 Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%.
The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population.
The relevance of several other studies is affected by small sample size (range, 36–85).3-6 Other studies did not attempt to biopsy all patients screened with ultrasound.7,8
Recommendations from others
The National Cancer Institute states finds the evidence insufficient to recommend any routine screening for endometrial cancer with either endometrial biopsy or transvaginal ultrasound. The American Cancer Society does not recommend routine screening of asymptomatic patients for endometrial cancer. They recommend prompt recognition and evaluation of abnormal uterine bleeding. The US Preventive Services Task Force and American Academy of Family Physicians have not issued recommendations related to endometrial cancer screening.
No need to screen postmenopausal women for endometrial disease
Paul V. Aitken, Jr., MD, MPH
New Hanover Regional Medical Center, Wilmington, NC/University of North Carolina at Chapel Hill
This Clinical Inquiry appears to draw appropriate conclusions to the question as presented. However, the question implies tacit approval of the notion of screening asymptomatic postmenopausal women. As pointed out above, no major organization recommends screening of these women. When reviewing a study we must also ask if the original study question is similar to our own clinical question. A critical piece of information regarding this answer is that references 1 and 2 are “nested” studies done within the context of large drug trials originally designed to answer very different questions. These asymptomatic women were being screened as part of the study protocol to ensure drug safety. Any effort on our part to apply this data to our asymptomatic patients should be considered with this significant limitation in mind.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
1. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Intervention Trial. N Engl J Med 1997;337:1792-1798.
2. Fleischer AC, Wheeler JE, Lindsay I, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet Gynecol 2001;184:70-75.
3. Hanggi W, Bersinger N, Altermatt HJ, Birkhauser MH. Comparison of transvaginal ultrasonography and endometrial biopsy in surveillance in postmenopausal HRT users. Maturitas 1997;27:133-143.
4. Shipley CF, 3rd, Simmons CL, Nelson GH. Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women. J Ultrasound Med 1994;13:99-104.
5. Paraskevaidis E, Papadimitriou D, Kalantaridou SN, et al. Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women. Anticancer Res 2002;22:1127-1130.
6. Castelo-Branco C, Puerto B, Duran M, et al. Transvaginal sonography of the endometrium in postmenopausal women: monitoring the effect of hormone replacement therapy. Maturitas 1994;19:59-65.
7. Vuento MH, Pirhonen JP, Makinen JI, et al. Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography. Br J Obstet Gynaecol 1999;106:14-20.
8. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M. A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography. Tumori 1995;81:334-337.
Evidence-based answers from the Family Physicians Inquiries Network
Are antibiotics effective in preventing pneumonia for nursing home patients?
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
8. Strassbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term care facilities. Infection Control and Hospital Epidemiology 1996;17:129-140.
9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-4):1-28.
10. Prevention of Pneumococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1-24.
11. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2002;51(RR-3):1-31.
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
Antibiotics should not be used for prophylaxis of pneumonia in nursing homes. We found no studies testing the effectiveness of antibiotics in preventing pneumonia in any population, including persons with predisposing conditions such as influenza. Three measures effectively prevent pneumonia in nursing home patients: influenza vaccination of residents (strength of recommendation [SOR]: B, based on systematic review of homogenous cohort observational studies); influenza vaccination of caregivers (SOR: B, based on individual randomized controlled trial); pneumococcal vaccination of residents (SOR: B, based on randomized, nonblinded clinical trials and consistent case-control studies).
Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.
Evidence summary
Overuse of antibiotics is already a problem in nursing homes. A large portion of bacterial pneumonia in the nursing home population results from aspiration of oropharyngeal bacteria, which is more likely to be drug-resistant if the resident has been on antibiotics.1 We found no studies that testing antibacterial agents for prevention of pneumonia in nursing home patients. However, 3 measures are clearly helpful in preventing pneumonia in nursing home patients:
- Influenza vaccination of residents: A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35–66)—defined as 1 minus the odds ratio—for influenza immunization in preventing pneumonia.2
- Influenza vaccination of caregivers: A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4–0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3).3
- Pneumococcal vaccination of residents: This evidence was reviewed in a prior Clinical Inquiry.4 The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35.
Two other proposed interventions require further study to evaluate their role in prophylaxis. Antiviral prophylaxis to prevent pneumonia during nursing home outbreaks of influenza has not been evaluated in controlled trials. Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes (Table). Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive.5,6 Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia.
Oral hygiene programs for nursing home residents may also reduce pneumonia. In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36–0.99; NNT=12.5) for pneumonia over a 2-year period.7 The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible.
TABLE
Available treatment and prophylactic regimens for influenza
| Drug name | Regimen for treatment* | Regimen for prophylaxis† | Comments | Cost‡ |
|---|---|---|---|---|
| Oseltamivir (Tamiflu) | 75 mg orally twice daily for 5 days | 75 mg orally once daily for >7 days | Influenza A and B | 10 tabs $59.99 (no generic) |
| Rimantidine (Flumadine) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only | 14 tabs $33.45 (no generic) |
| Amantadine (Symmetrel) | 100 mg orally twice daily (100 mg orally once daily in elderly) | 100 mg orally twice daily (100 mg orally once daily in elderly) | Influenza A only (consider lower doses in debilitated patients) | 60 tabs $75.58 (brand), $18.99 (generic) |
| Zanamivir (Relenza) | 2 inhalations (10 mg) every 12 hours for 5 days | Not indicated | Influenza A and B (inhalations may be difficult to administer to debilitated patients) | 20 inhalation doses $54.41 (no generic) |
| Source: Epocrates RX: Online and PDA-Based Reference, June 12, 2004. | ||||
| * Start treatment within 48 hours of onset of symptoms. | ||||
| † Start prophylaxis immediately or within 48 hours of exposure. | ||||
| ‡ Approximate retail price from www.drugstore.com, June 2004. | ||||
Recommendations from others
There are no recommendations about the use of antibiotic prophylaxis for pneumonia in either the nursing home or in the outpatient settings; however, there are clear recommendations against the overuse of antibiotics.8
The CDC Advisory Committee on Immunization Practices (ACIP) recommends:
- annual influenza vaccine for persons residing in nursing homes9
- annual influenza vaccine for health care workers in long-term care facilities9
- pneumococcal vaccine for persons residing in a nursing home (the schedule for an immunocompetent adult is a single dose, followed by a booster after age 65 if the first dose was before age 65, or after 5 years for persons <65 years with compromised immune status)10
- chemoprophylaxis for influenza outbreaks in nursing homes.11
Prevention is key for reducing pneumonia mortality
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Pneumonia is one of the most common causes of death for nursing home patients. While pneumonia can present with the classic fever, productive cough, and air hunger, it often presents with such nonspecific findings as altered mental status or mild tachypnea, which can significantly delay diagnosis. Additionally, many older adults poorly tolerate the metabolic demands of the disease and become critically ill very rapidly. Thus, prevention remains a key strategy for reducing mortality. Nursing home policies that facilitate vaccination and reduce disease transmission are critically important in this regard.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
8. Strassbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term care facilities. Infection Control and Hospital Epidemiology 1996;17:129-140.
9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-4):1-28.
10. Prevention of Pneumococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1-24.
11. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2002;51(RR-3):1-31.
1. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc 2001;49:85-90.
2. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527.
3. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6.
4. McCormack O, Meza J, Martin S, Tatum P. Is pneumococcal vaccine effective in nursing home patients? J Fam Pract 2003;52:150-154.
5. Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home. Arch Intern Med 1988;148:865-868.
6. Parker R, Loewen N, Skowronski D. Experience with oseltamivir in the control of a nursing home influenza B outbreak. Can Commun Dis Rep 2001;27:37-40.
7. Yoneyama T, Yoshida M, Ohrui T, et al. Oral care reduces pneumonia in older patients in nursing homes. J Am Geriatr Soc 2002;50:430-433.
8. Strassbaugh LJ, Crossley KB, Nurse BA, Thrupp LD. Antimicrobial resistance in long-term care facilities. Infection Control and Hospital Epidemiology 1996;17:129-140.
9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-4):1-28.
10. Prevention of Pneumococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1-24.
11. Bridges CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA. Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2002;51(RR-3):1-31.
Evidence-based answers from the Family Physicians Inquiries Network
Is the ThinPrep better than conventional Pap smear at detecting cervical cancer?
Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer (strength of recommendation [SOR]: A–, based on 1 large validating cohort study with a good reference standard and 1 systematic review). There is insufficient evidence to recommend 1 preparation over the other (SOR: B–, based on several systematic reviews that include studies with poor reference standards).
The ThinPrep is a cost-effective screening tool if used at 3-year intervals (SOR: B, based on 1 systematic review and a decision analysis model). Additional advantages of the ThinPrep include being able to perform human papillomavirus (HPV) testing on the liquid. This is the preferred triage strategy for atypical squamous cells of undetermined significance (ASCUS) Pap smears (SOR: A, based on a large randomized, controlled trial).
Evidence summary
The conventional Pap smear is the standard screening test for cervical neoplasia. Despite success, the Pap smear has high false-negative rates due to poor sensitivity (51%; 95% confidence interval [CI], 37%–66%).1 The ThinPrep was developed to improve sensitivity by providing a monolayer of cells to the cytologist for review. A population-based comparative analysis of good quality shows that the new technology is better at detecting cancer precursors, but other systematic reviews that include less rigorous studies can only suggest it.
The overwhelming problem with most studies is they lack adequate reference standards. Customary criteria for evaluating diagnostic tests require that a “gold standard” reference be used, and that both the abnormal and normal results are validated against it. For cervical cancer screening, the “gold standard” is histology.
Only 1 analysis met the standard criteria. This prospective, population-based study of 8636 women reported that the ThinPrep was significantly more sensitive than the conventional smears at detecting high-grade squamous intraepithelial lesions (HSIL) and cancer, with sensitivity rates of 92.9% and 100% vs 77.8% and 90.9%, respectively (P<.001).2 This evidence demonstrates that the ThinPrep is better at detecting cervical cancer.
Several systematic reviews summarize the many studies that compare ThinPrep with the conventional Pap. Unfortunately, conclusions are difficult to interpret. A recent quantitative review implies that the ThinPrep increases cytologic diagnoses of cervical cancer and its precursors.3 A strength of this review is the inclusion of 10 articles with histology as the reference standard. The data from 21,752 patients compared the sensitivity and specificity rates of Thin Prep with conventional Pap for detecting abnormal histology. Sensitivity rates were reported as 76% (ThinPrep) and 68% (conventional), but the differences met statistical significance in only 2 of the included studies. Similarly, the overall specificity rates of the ThinPrep vs conventional Pap was 86% vs 79%, and again the differences did not usually reach statistical significance. The authors hypothesize that widespread use of ThinPrep could potentially detect an additional 162,000 patients with HSIL and 3000 patients with invasive cervical carcinoma.
A large meta-analysis of 25 prospective studies including over 500,000 women reported that ThinPrep increased detection of low-grade squamous intraepithelial lesions (LSIL) (odds ratio [OR]=2.15; 95% CI, 2.05–2.26) and HSIL (OR=2.26; 95% CI, 1.53–1.76), but the conclusions were severely limited by lack of a reference standard and high heterogeneity between study populations.4 Another review found insufficient evidence to even judge the new test.5
A large evidence review done for the Agency for Healthcare Research and Quality (AHRQ) concluded that the quality of the available literature is poor. Two of the 3 trials reviewed had major methodological flaws that prevented an appropriate comparison of the data to show a modestly higher sensitivity of the ThinPrep.1 From these reviews, we cannot recommend one technique over the other.
When evaluating a new screening test, cost is important. The AHRQ review1 and a modeled cost and outcomes analysis6 concluded that liquid-based cytology falls within the accepted ranges of cost-effectiveness if used at 3-year screening intervals. Another computer-based model evaluated different triage strategies for ASCUS Pap smears and found that reflex HPV testing provides the same or greater life expectancy benefits and is more cost-effective.7 This strategy requires the use of liquid-based cytology. The large ALTS trial supports the use of liquid-based cytology because it has shown HPV testing in patients with ASCUS decreases the need for colposcopy.8 Ultimately, when deciding which Pap test is better, many things in addition to sensitivity must be considered.
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. They acknowledge that ThinPrep may have improved sensitivity over conventional Pap smears but may possibly have lower specificity. The Task Force notes that ThinPrep could be cost-effective with longer screening intervals and can be helpful for the management of ASCUS.9
No current screening guidelines specifically recommend newer Pap test technologies in favor of conventional Pap tests. These associations include American Cancer Society, American Academy of Family Physicians, American College of Preventive Medicine, and American College of Gynecology.
ThinPrep’s high sensitivity and viral typing may be advantageous in some cases
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
Because the ThinPrep is expensive and not endorsed by major medical policy groups, it is not time for family physicians to switch to the ThinPrep en masse.However, I think 2 groups will be looking carefully at this technology.
First, in settings where annual follow-up is unreliable or impractical, the ThinPrep’s high sensitivity will definitely be advantageous. Second, physicians who want to use HPV-based colposcopy guidelines will appreciate the ThinPrep’s viral typing capabilities, although the unresolved issue of screening frequency will remain a problem. Advertising pressures, advocacy groups, and payer response will also shape this ongoing discussion.
1. McCrory DC, Mather DB, Bastian L. Evaluation of Cervical Cytology: Evidence Report Number 5, Summary. Rockville, Md: Agency for Health Care Policy and Research; 1999. Available at: www.ahcpr.gov/clinic/epcsums/cervsumm.htm. Accessed on March 9, 2004.
2. Hutchinson ML, Zahniser DJ, Sherman ME, et al. Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. Cancer 1999;87:48-55.
3. Abulafia O, Pezzullo JC, Shere DV. Performance of ThinPrep liquid-based cervical cytology in comparison with conventionally prepared Papanicolaou smears: a quantitative survey. Gynecologic Oncology 2003;90:137-144.
4. Bernstein SJ, Sanchez-Ramos L, Ndubisi B. Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A meta-analysis of prospective studies comparing cytologic diagnosis and sample adequacy. Am J Obstet Gynecol 2001;185:308-317.
5. Nanda K, McCrory DC, Myers ER, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;132:810-819.
6. Montz FJ, Farber FL, Bristow RE, et al. Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost and outcomes analysis. Obstet Gynecol 2001;97:781-788.
7. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA 2002;287:2382-2390.
8. Solomon D, Schiffman M, Tarone R. for the ALTS Study group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001;93:293-299.
9. US Preventive Services Task Force. Screening for cervical cancer: recommendations and rationale. Am J Nurs 2003;103:101-109.
Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer (strength of recommendation [SOR]: A–, based on 1 large validating cohort study with a good reference standard and 1 systematic review). There is insufficient evidence to recommend 1 preparation over the other (SOR: B–, based on several systematic reviews that include studies with poor reference standards).
The ThinPrep is a cost-effective screening tool if used at 3-year intervals (SOR: B, based on 1 systematic review and a decision analysis model). Additional advantages of the ThinPrep include being able to perform human papillomavirus (HPV) testing on the liquid. This is the preferred triage strategy for atypical squamous cells of undetermined significance (ASCUS) Pap smears (SOR: A, based on a large randomized, controlled trial).
Evidence summary
The conventional Pap smear is the standard screening test for cervical neoplasia. Despite success, the Pap smear has high false-negative rates due to poor sensitivity (51%; 95% confidence interval [CI], 37%–66%).1 The ThinPrep was developed to improve sensitivity by providing a monolayer of cells to the cytologist for review. A population-based comparative analysis of good quality shows that the new technology is better at detecting cancer precursors, but other systematic reviews that include less rigorous studies can only suggest it.
The overwhelming problem with most studies is they lack adequate reference standards. Customary criteria for evaluating diagnostic tests require that a “gold standard” reference be used, and that both the abnormal and normal results are validated against it. For cervical cancer screening, the “gold standard” is histology.
Only 1 analysis met the standard criteria. This prospective, population-based study of 8636 women reported that the ThinPrep was significantly more sensitive than the conventional smears at detecting high-grade squamous intraepithelial lesions (HSIL) and cancer, with sensitivity rates of 92.9% and 100% vs 77.8% and 90.9%, respectively (P<.001).2 This evidence demonstrates that the ThinPrep is better at detecting cervical cancer.
Several systematic reviews summarize the many studies that compare ThinPrep with the conventional Pap. Unfortunately, conclusions are difficult to interpret. A recent quantitative review implies that the ThinPrep increases cytologic diagnoses of cervical cancer and its precursors.3 A strength of this review is the inclusion of 10 articles with histology as the reference standard. The data from 21,752 patients compared the sensitivity and specificity rates of Thin Prep with conventional Pap for detecting abnormal histology. Sensitivity rates were reported as 76% (ThinPrep) and 68% (conventional), but the differences met statistical significance in only 2 of the included studies. Similarly, the overall specificity rates of the ThinPrep vs conventional Pap was 86% vs 79%, and again the differences did not usually reach statistical significance. The authors hypothesize that widespread use of ThinPrep could potentially detect an additional 162,000 patients with HSIL and 3000 patients with invasive cervical carcinoma.
A large meta-analysis of 25 prospective studies including over 500,000 women reported that ThinPrep increased detection of low-grade squamous intraepithelial lesions (LSIL) (odds ratio [OR]=2.15; 95% CI, 2.05–2.26) and HSIL (OR=2.26; 95% CI, 1.53–1.76), but the conclusions were severely limited by lack of a reference standard and high heterogeneity between study populations.4 Another review found insufficient evidence to even judge the new test.5
A large evidence review done for the Agency for Healthcare Research and Quality (AHRQ) concluded that the quality of the available literature is poor. Two of the 3 trials reviewed had major methodological flaws that prevented an appropriate comparison of the data to show a modestly higher sensitivity of the ThinPrep.1 From these reviews, we cannot recommend one technique over the other.
When evaluating a new screening test, cost is important. The AHRQ review1 and a modeled cost and outcomes analysis6 concluded that liquid-based cytology falls within the accepted ranges of cost-effectiveness if used at 3-year screening intervals. Another computer-based model evaluated different triage strategies for ASCUS Pap smears and found that reflex HPV testing provides the same or greater life expectancy benefits and is more cost-effective.7 This strategy requires the use of liquid-based cytology. The large ALTS trial supports the use of liquid-based cytology because it has shown HPV testing in patients with ASCUS decreases the need for colposcopy.8 Ultimately, when deciding which Pap test is better, many things in addition to sensitivity must be considered.
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. They acknowledge that ThinPrep may have improved sensitivity over conventional Pap smears but may possibly have lower specificity. The Task Force notes that ThinPrep could be cost-effective with longer screening intervals and can be helpful for the management of ASCUS.9
No current screening guidelines specifically recommend newer Pap test technologies in favor of conventional Pap tests. These associations include American Cancer Society, American Academy of Family Physicians, American College of Preventive Medicine, and American College of Gynecology.
ThinPrep’s high sensitivity and viral typing may be advantageous in some cases
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
Because the ThinPrep is expensive and not endorsed by major medical policy groups, it is not time for family physicians to switch to the ThinPrep en masse.However, I think 2 groups will be looking carefully at this technology.
First, in settings where annual follow-up is unreliable or impractical, the ThinPrep’s high sensitivity will definitely be advantageous. Second, physicians who want to use HPV-based colposcopy guidelines will appreciate the ThinPrep’s viral typing capabilities, although the unresolved issue of screening frequency will remain a problem. Advertising pressures, advocacy groups, and payer response will also shape this ongoing discussion.
Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer (strength of recommendation [SOR]: A–, based on 1 large validating cohort study with a good reference standard and 1 systematic review). There is insufficient evidence to recommend 1 preparation over the other (SOR: B–, based on several systematic reviews that include studies with poor reference standards).
The ThinPrep is a cost-effective screening tool if used at 3-year intervals (SOR: B, based on 1 systematic review and a decision analysis model). Additional advantages of the ThinPrep include being able to perform human papillomavirus (HPV) testing on the liquid. This is the preferred triage strategy for atypical squamous cells of undetermined significance (ASCUS) Pap smears (SOR: A, based on a large randomized, controlled trial).
Evidence summary
The conventional Pap smear is the standard screening test for cervical neoplasia. Despite success, the Pap smear has high false-negative rates due to poor sensitivity (51%; 95% confidence interval [CI], 37%–66%).1 The ThinPrep was developed to improve sensitivity by providing a monolayer of cells to the cytologist for review. A population-based comparative analysis of good quality shows that the new technology is better at detecting cancer precursors, but other systematic reviews that include less rigorous studies can only suggest it.
The overwhelming problem with most studies is they lack adequate reference standards. Customary criteria for evaluating diagnostic tests require that a “gold standard” reference be used, and that both the abnormal and normal results are validated against it. For cervical cancer screening, the “gold standard” is histology.
Only 1 analysis met the standard criteria. This prospective, population-based study of 8636 women reported that the ThinPrep was significantly more sensitive than the conventional smears at detecting high-grade squamous intraepithelial lesions (HSIL) and cancer, with sensitivity rates of 92.9% and 100% vs 77.8% and 90.9%, respectively (P<.001).2 This evidence demonstrates that the ThinPrep is better at detecting cervical cancer.
Several systematic reviews summarize the many studies that compare ThinPrep with the conventional Pap. Unfortunately, conclusions are difficult to interpret. A recent quantitative review implies that the ThinPrep increases cytologic diagnoses of cervical cancer and its precursors.3 A strength of this review is the inclusion of 10 articles with histology as the reference standard. The data from 21,752 patients compared the sensitivity and specificity rates of Thin Prep with conventional Pap for detecting abnormal histology. Sensitivity rates were reported as 76% (ThinPrep) and 68% (conventional), but the differences met statistical significance in only 2 of the included studies. Similarly, the overall specificity rates of the ThinPrep vs conventional Pap was 86% vs 79%, and again the differences did not usually reach statistical significance. The authors hypothesize that widespread use of ThinPrep could potentially detect an additional 162,000 patients with HSIL and 3000 patients with invasive cervical carcinoma.
A large meta-analysis of 25 prospective studies including over 500,000 women reported that ThinPrep increased detection of low-grade squamous intraepithelial lesions (LSIL) (odds ratio [OR]=2.15; 95% CI, 2.05–2.26) and HSIL (OR=2.26; 95% CI, 1.53–1.76), but the conclusions were severely limited by lack of a reference standard and high heterogeneity between study populations.4 Another review found insufficient evidence to even judge the new test.5
A large evidence review done for the Agency for Healthcare Research and Quality (AHRQ) concluded that the quality of the available literature is poor. Two of the 3 trials reviewed had major methodological flaws that prevented an appropriate comparison of the data to show a modestly higher sensitivity of the ThinPrep.1 From these reviews, we cannot recommend one technique over the other.
When evaluating a new screening test, cost is important. The AHRQ review1 and a modeled cost and outcomes analysis6 concluded that liquid-based cytology falls within the accepted ranges of cost-effectiveness if used at 3-year screening intervals. Another computer-based model evaluated different triage strategies for ASCUS Pap smears and found that reflex HPV testing provides the same or greater life expectancy benefits and is more cost-effective.7 This strategy requires the use of liquid-based cytology. The large ALTS trial supports the use of liquid-based cytology because it has shown HPV testing in patients with ASCUS decreases the need for colposcopy.8 Ultimately, when deciding which Pap test is better, many things in addition to sensitivity must be considered.
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. They acknowledge that ThinPrep may have improved sensitivity over conventional Pap smears but may possibly have lower specificity. The Task Force notes that ThinPrep could be cost-effective with longer screening intervals and can be helpful for the management of ASCUS.9
No current screening guidelines specifically recommend newer Pap test technologies in favor of conventional Pap tests. These associations include American Cancer Society, American Academy of Family Physicians, American College of Preventive Medicine, and American College of Gynecology.
ThinPrep’s high sensitivity and viral typing may be advantageous in some cases
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
Because the ThinPrep is expensive and not endorsed by major medical policy groups, it is not time for family physicians to switch to the ThinPrep en masse.However, I think 2 groups will be looking carefully at this technology.
First, in settings where annual follow-up is unreliable or impractical, the ThinPrep’s high sensitivity will definitely be advantageous. Second, physicians who want to use HPV-based colposcopy guidelines will appreciate the ThinPrep’s viral typing capabilities, although the unresolved issue of screening frequency will remain a problem. Advertising pressures, advocacy groups, and payer response will also shape this ongoing discussion.
1. McCrory DC, Mather DB, Bastian L. Evaluation of Cervical Cytology: Evidence Report Number 5, Summary. Rockville, Md: Agency for Health Care Policy and Research; 1999. Available at: www.ahcpr.gov/clinic/epcsums/cervsumm.htm. Accessed on March 9, 2004.
2. Hutchinson ML, Zahniser DJ, Sherman ME, et al. Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. Cancer 1999;87:48-55.
3. Abulafia O, Pezzullo JC, Shere DV. Performance of ThinPrep liquid-based cervical cytology in comparison with conventionally prepared Papanicolaou smears: a quantitative survey. Gynecologic Oncology 2003;90:137-144.
4. Bernstein SJ, Sanchez-Ramos L, Ndubisi B. Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A meta-analysis of prospective studies comparing cytologic diagnosis and sample adequacy. Am J Obstet Gynecol 2001;185:308-317.
5. Nanda K, McCrory DC, Myers ER, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;132:810-819.
6. Montz FJ, Farber FL, Bristow RE, et al. Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost and outcomes analysis. Obstet Gynecol 2001;97:781-788.
7. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA 2002;287:2382-2390.
8. Solomon D, Schiffman M, Tarone R. for the ALTS Study group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001;93:293-299.
9. US Preventive Services Task Force. Screening for cervical cancer: recommendations and rationale. Am J Nurs 2003;103:101-109.
1. McCrory DC, Mather DB, Bastian L. Evaluation of Cervical Cytology: Evidence Report Number 5, Summary. Rockville, Md: Agency for Health Care Policy and Research; 1999. Available at: www.ahcpr.gov/clinic/epcsums/cervsumm.htm. Accessed on March 9, 2004.
2. Hutchinson ML, Zahniser DJ, Sherman ME, et al. Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. Cancer 1999;87:48-55.
3. Abulafia O, Pezzullo JC, Shere DV. Performance of ThinPrep liquid-based cervical cytology in comparison with conventionally prepared Papanicolaou smears: a quantitative survey. Gynecologic Oncology 2003;90:137-144.
4. Bernstein SJ, Sanchez-Ramos L, Ndubisi B. Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A meta-analysis of prospective studies comparing cytologic diagnosis and sample adequacy. Am J Obstet Gynecol 2001;185:308-317.
5. Nanda K, McCrory DC, Myers ER, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;132:810-819.
6. Montz FJ, Farber FL, Bristow RE, et al. Impact of increasing Papanicolaou test sensitivity and compliance: a modeled cost and outcomes analysis. Obstet Gynecol 2001;97:781-788.
7. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA 2002;287:2382-2390.
8. Solomon D, Schiffman M, Tarone R. for the ALTS Study group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001;93:293-299.
9. US Preventive Services Task Force. Screening for cervical cancer: recommendations and rationale. Am J Nurs 2003;103:101-109.
Evidence-based answers from the Family Physicians Inquiries Network