Are US Cervical Cancer Screening Exit Criteria Failing?

Cervical cancer screening guidelines in the United States have evolved considerably over the past few decades, reflecting advances in understanding how cervical cancer develops, the pivotal role that human papillomavirus (HPV) plays in driving carcinogenesis, and improved screening techniques.

Despite these changes, concerns persist about whether current exit criteria — the guidelines for discontinuing screening in women of a certain age — are achieving their intended purpose of minimizing harm while preventing disease. 

Guidelines recommend that women over age 65 years who have had adequate prior cervical cancer screening can stop because, beyond this point, women face a low risk for cervical cancer and cancer death. 

Findings from a recent modeling study align with the recommendation. The analysis, published in JAMA Network Open, predicted low rates of cervical cancer and cancer death for women who meet criteria to exit screening.

Real-world data, however, tell a different story: Cervical cancer incidence and mortality rates remain relatively high among older women, according to Rebecca B. Perkins, MD, MSc, from Tufts Medical Center, Boston, and Sarah Feldman, MD, MPH, from Brigham and Women’s Hospital, writing in an invited commentary published alongside the modeling study. 

Are US cervical cancer screening criteria for when to stop screening failing? Or do modeling studies miss the mark on estimating risk? 

What’s the History of Exit Criteria Advice? 

In 2012, guidelines from the American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology, and US Preventive Services Task Force (USPSTF) were aligned in their recommendation against screening for cervical cancer in women over 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. In 2018, the USPSTF reaffirmed this recommendation.

Adequate screening is defined as either three consecutive negative Pap tests or two consecutive negative concurrent HPV and Pap test results (co-testing) within 10 years preceding age 65, with the most recent test administered within the past 5 years. 

According to the USPSTF, screening should begin at age 21, with Pap tests recommended every 3 years throughout that decade. Beginning at age 30, screening options can include Pap tests every 3 years, HPV tests every 5 years, or a combination every 5 years until age 65.

The goal of exit criteria is to reduce overscreening and related harms, such as unnecessary colposcopies and biopsies, patient anxiety, and increased healthcare costs, in women deemed low risk for cervical cancer. This approach aligns with the well-established principle of risk stratification in cancer screening programs. 

Yet, the optimal age and method for stopping cervical cancer screening remains controversial. 

The USPSTF recommendations were based on a modeling analysis commissioned by the Task Force, which “projected that extending screening beyond age 65 years in women with an adequate screening history would not have significant benefit.”

But even the USPSTF has acknowledged that “the epidemiologic evidence to support a definitive age to end screening in older females is lacking,” according to Shalini Kulasingam, PhD, first author on the modeling study, and colleagues.

What the New Modeling Study Found 

In the recent modeling study, Kulasingam and colleagues explored the risk for cervical cancer and cervical cancer death among women who met current US criteria to stop cervical cancer screening. 

The team used a modeling approach that incorporated different screening histories to estimate the risk for cervical intraepithelial neoplasia grade 3, cervical cancer, and cervical cancer deaths in a cohort of women not vaccinated against HPV and who were representative of women transitioning out of screening in the US healthcare setting.

Across various screening history scenarios, all models estimated a low risk for subsequently developing or dying from cervical cancer, although the risk increased with age and/or time since screening exit, the team found. 

In one scenario, in which women had no screening before age 60, the cumulative risks for cervical cancer by age 70 years ranged from 0.001% to 0.003% and the risks for cervical cancer death ranged from 0% to 0.001%. By age 85 years, the cumulative risks for cervical cancer ranged from 0.026% to 0.081% and risks for cervical cancer death ranged from 0.005% to 0.038%. 

Beyond Modeling: What’s Happening in Practice? 

For a variety of reasons, these types of models may yield “unrealistically” low cancer estimates, Perkins and Feldman cautioned in their commentary. 

Perkins and Feldman explained that the low rates of cervical cancer found in this modeling study contrast with the relatively high rates observed in practice. For example, in the US, more than 20% of cervical cancers occur in women older than 65 years, and mortality rates are much higher in older women.

Discrepancies between model predictions and clinical experience may stem from a lack of adherence to screening recommendations at older ages, but modeling studies assume adherence, Perkins and Feldman noted. 

Research suggests, for instance, that women aged 60-64 years are less than half as likely to get screened for cervical cancer compared with those aged 30-39 years. Studies assessing adherence to screening exit guidelines have reported substantial underscreening in women aged 64-66, with only 1 in 3 fulfilling criteria to discontinue screening. 

And unless screening gaps are addressed, cervical cancer rates among women older than 65 years probably will continue to trend upward over time for a variety of reasons, Perkins and Feldman said. 

“First, more women are aging with their cervix in place due to lower hysterectomy rates compared with prior cohorts,” the experts explained. 

“Second, women born before HPV vaccination was widely available and who undergo less frequent screening than prior generations may have higher rates of both HPV infection and undetected abnormalities than previous generations, further increasing cancer risks.”

Plus, they added, “new data indicate that a proportion of HPV infections reactivate after a period of latency and that reactivations are associated with high-grade lesions.” 

Time to Update Exit Criteria? 

The immediate clinical and policy implications of the modeling study are not clear at the moment, Kulasingam told Medscape Medical News.

“This study is a first step towards determining if there are more effective and cost-effective strategies that are easy to implement and can be used to safely exit women from cervical cancer screening,” said Kulasingam, with the School of Public Health, University of Minnesota, Minneapolis. 

However, “a growing body of evidence suggests that documenting a woman’s screening history to determine if she’s eligible to exit screening is difficult,” Kulasingam added. 

For example, in two US large health systems, about 69% of patients lacked sufficient data in the electronic health record to meet criteria to exit cervical cancer screening by age 65 years. 

Perkins and Feldman echoed this issue with tracking screening exit eligibility. 

Mounting data indicate that requiring clinicians to access 10-25 years of prior results to determine screening exit eligibility is “not feasible,” they wrote. Obtaining historical medical records is “cumbersome, time consuming, and not reimbursable.”

One solution supported by the modeling study is that all women at average risk and with a cervix undergo two cervical cancer screenings with HPV testing between age 60 and 65 years, Perkins and Feldman said. 

That would be “more practical and actionable than current recommendations that require clinicians to perform retrospective electronic medical record review for each patient.” 

And this type of exit advice would provide direct, unambiguous education to clinicians and the lay public. “This could address issues related to lack of awareness and inability to enact current recommendations,” Perkins and Feldman said. 

Perkins and Feldman say it’s equally important for women and their healthcare providers to be aware of factors that increase cervical cancer risk and require screening beyond age 65 years. According to guidelines, these factors include a prior abnormal Pap test or positive HPV test results at age 55 or older; a history of cervical precancer at age 40 years or older; immunosuppression, including HIV infection; solid organ transplant; use of medications with significant immunosuppressive effects; and any history of cervical cancer. 

The USPSTF is currently revising its cervical cancer screening guidelines and has the opportunity to address exit criteria. 

Media relations for the USPSTF did not respond to requests made by Medscape Medical News for comment on this issue, but in draft recommendations released last December, the USPSTF continued to conclude that the benefits of continued screening may not outweigh harms for women older than 65 who have had adequate prior screening with normal results and are not at high risk.