Sarah Dilley, MD, MPH

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.