Study Assesses Risks of Cervical Cancer Outcomes for Women Exiting Screening at Age 65

Cervical cancer screening guidelines in the U.S. recommend that most women can discontinue routine screening at age 65 after receiving two consecutive negative cotests, which involve concurrent human papillomavirus (HPV) and Papanicolaou (Pap) tests. However, empirical data on cancer and mortality risks for this demographic group remain sparse. A decision analytical comparative modeling study was conducted to estimate risks of cervical cancer and associated mortality for women who meet the exit criteria. Recent study utilized four distinct models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and validated them against published data on cervical intraepithelial neoplasia grade 3 (CIN3) risks from a Kaiser Permanente Northern California (KPNC) cohort.

Model Outcomes and Analysis

With attention to both age-conditional and cumulative risks of cervical cancer and cancer death, the models generated outcomes for women aged 65, 70, 75, 80, and 85 years. Following the harmonized guidelines established in 2012, which reaffirmed the exit criteria based on adequate screening, the analysis sought to delineate cancer risks for those who had shown consistent negative results.

Microsimulations and Findings

The models involved microsimulations calibrated using U.S. epidemiologic data and facilitated comparisons of cancer risk under various screening histories. The findings highlighted that the 3-year risk for CIN3 for two consecutive negative results ranged from approximately 0.035% to 0.038%, marginally exceeding published bounds from the KPNC cohort, while the 5-year risks aligned within the accepted confidence interval, reflecting an estimated incidence of 0.075% to 0.083%.

Age-Conditional Risks Evaluation

In evaluating age-conditional risks, results indicated that, while the risks were generally low across both groups, lower age-conditional risks of cervical cancer and mortality were projected for those with comprehensive screening histories compared to those with only the two negative results when exiting screening. However, one of the models (Policy1-Cervix) produced a discrepancy, predicting higher risks in certain age brackets, suggesting variability among models stemming from different assumptions about cancer progression pathways.

Cumulative Risk Projections

Cumulatively, risks of cervical cancer by age 85 were projected to be between 0.026% and 0.081%, with mortality risks also being low (ranging from 0.005% to 0.038%). Interestingly, scenarios applying lower sensitivity for cytology tests and increased HPV incidence showed a slight escalation in these risks, underscoring the complexity of HPV theory in relation to cervical cancer risk. The present findings represent the first comprehensive estimates pertaining to this specific subset of older women and reaffirm the consequential role of rigorous screening in risk management. Despite the study’s insights, limitations were noted, including potential demographic disparities in the KPNC population and constraints surrounding various screening cessation criteria. Future guidelines should consider a broader spectrum of screening cessation strategies given the persistent uncertainties surrounding HPV incidence among aging cohorts. The analysis advocates for an intricate balance between minimizing cancer risks and evaluating screening-related harms and benefits, especially in the context of competing health concerns that accompany aging women. Continued surveillance of HPV prevalence should be prioritized to inform evolving cervical screening recommendations.

Key Points

- Cervical cancer screening in the U.S. allows most women to stop routine screening at age 65 after two consecutive negative HPV and Pap tests, but data on cancer and mortality risks for this age group is limited. A comparative modeling study aimed to fill this knowledge gap.

- The study employed four models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate cancer and mortality risks in women aged 65 to 85, using data from a Kaiser Permanente Northern California cohort for validation.

- Microsimulations demonstrated that the 3-year risk for cervical intraepithelial neoplasia grade 3 (CIN3) after two negative tests was between 0.035% and 0.038%, with 5-year risks falling within acceptable confidence intervals, estimated at 0.075% to 0.083%.

- Age-conditional risks revealed that women with comprehensive screening histories exhibited lower cervical cancer and mortality risks compared to those who had only the necessary two negative results. However, one of the models predicted higher risks for certain age groups, indicating variability in model outcomes based on different cancer progression assumptions.

- Cumulative risk projections indicated a cervical cancer risk by age 85 of 0.026% to 0.081%, with associated mortality risks ranging from 0.005% to 0.038%. Increased HPV incidence and lower sensitivity in cytology tests were associated with slight increases in these risks.

- The study acknowledged demographic disparities in the data and the need for future guidelines to account for varied screening cessation strategies, emphasizing the importance of balancing cancer risk reduction with the assessment of screening-related benefits and harms in aging populations. Ongoing monitoring of HPV prevalence is crucial for adapting cervical screening recommendations.

Reference –

Shalini L Kulasingam et al. (2025). Estimated Cancer Risk In Females Who Meet The Criteria To Exit Cervical Cancer Screening. *JAMA Network Open*, 8. https://doi.org/10.1001/jamanetworkopen.2025.0479.