WHEN TO STOP CERVICAL CANCER SCREENING

The value of cervical cancer screening in young and middle-aged women is established, but its utility for women 55 years of age or older has remained an open question. Now a new modeling study suggests that women can benefit from regular cytology screening (pap smear) up to 75 years of age, and those screened with the newer high-risk human papillomavirus (HPV) test can stop at age 55 years as long as their final test is negative.

The study was designed to apply to older women who live in wealthy nations that have established cervical cancer screening programs but who have not been vaccinated against HPV, lead author Talia Malagon, PhD, of the Division of Cancer Epidemiology, Department of Oncology, McGill University, Montreal, Quebec, Canada, and colleagues explain in their article published online November 1 in The Lancet Oncology.

The HPV vaccine was first licensed for use in 2006.

Worldwide recommendations for the age at which women can stop cervical cancer screening vary between 50 and 70 years of age, but that advice is based on low-quality evidence, and the incidence and mortality rates associated with cervical cancer remain high in older women, the authors write.

The Pap or cytology test, which identifies cervical cells that may appear abnormal because they are precancerous or for other reasons such as inflammation, is inexpensive and widely used.

The newer HPV test, which detects DNA or RNA from high-risk HPV in cervical cells and is gaining in popularity, "is associated with a 70% lower incidence of invasive cervical carcinoma compared with a negative cytology screen between the ages of 20 to 65 years," Malagon and colleagues explain.

Whether older women have a similarly lower risk after a negative exit HPV test or HPV and cytology co-test remained unclear.

In an accompanying commentary, Paolo Giorgi Rossi, PhD, of the Epidemiology Unit, Azienda Unità Sanitaria Locale, Reggio Emilia, Italy, writes that the age at which women can safely stop cervical cancer screening is "one of the most neglected issues in screening research."

Since 2012, international guidelines have used 60 to 65 years of age as the cutoff, "but to our knowledge, no data have been previously reported to support the chosen upper age limit to stop HPV-based cervical cancer screening," he notes.

In this study, Rossi adds, the authors have presented data "that are useful to guide decision making on the basis of the evidence, resources, and values we have."

Negative HPV Test Much More Predictive of Low Risk Than Pap Smear

In this study, "for a typical woman with average screening adherence," one negative cytology test before 70 years of age was not enough to indicate a long-term reduction in cervical cancer risk. "Therefore, additional screening might be warranted for a woman with an inadequate screening history in a cytology screening context," say the authors.

However, "a single negative HPV test or co-test after age 55 years indicated a very low remaining lifetime risk of cervical cancer," they write. "These results align with empirical data in younger women, showing the negative predictive value of a negative HPV test is much higher than that of a normal cytology test."

The findings suggest that a woman's decision to stop undergoing cervical cancer screening at age 55 years or more depends on the type of screening test used, Malagon explains in a press release about the study.

"For countries that still use cytology screening, screening at older ages should further reduce the risk of cervical cancer. However, our results suggest that for countries that use HPV testing as part of their screening, it might be possible to stop screening earlier than we are currently doing, provided women have a negative HPV test."

This study did not include any cost-effectiveness analysis, "which will be a useful next step to inform policy decisions before any change in guidance is considered," Malagon said in the release.

Cervical Cancer Likely Underestimated if Hysterectomies Not Excluded 

For the study, the authors developed a model of cervical cancer natural history and screening, which was calibrated and validated using information from Canadian provincial registries and surveys and included data on 236,564 women, or one fifth of Canadian women 20 to 24 years of age in 2012.

As a reference point, they used a base case scenario that reflected actual cervical cancer screening rates, "with 53% to 68% of women aged 20 to 69 years being screened at least once in the last 42 months, depending on age."

The analysis also accounted for women with hysterectomies and suggests that "the incidence of cervical cancer in women with a cervix is probably considerably underestimated in those aged 40 years and older when hysterectomies are not excluded from denominators," the authors explain.

From this model, the authors predict that, without screening or vaccination, 1 in 45 women would be diagnosed with cervical cancer in their lifetime.

With typical adherence to cytology screening, a woman who stops screening at 55 years of age would have a lifetime risk of 1 in 138. Were she to stop screening at age 70 years, her lifetime risk would be 1 in 160.

These findings suggest that "a substantial part of the reduction in the cumulative lifetime risk at older ages is due to screening before the age of 55 years (compared with no screening)," the authors explain.

With perfect adherence to the recommended cytology screening schedule of every 3 years for women aged 25 to 69 years, the lifetime risk for an unvaccinated woman would be 1 in 532.

Risk After Stopping Cytology Screening Depends on Age at Stoppage 

If a woman were to cease all cytology screening, the impact on her risk of cervical cancer would depend on the age at which she stopped, the authors add.

"Each 5-year delay in the age at which screening stopped, up until age 75 years, led to incremental reductions in later cervical cancer incidence. We predict that a woman with a cervix who stopped cytology screening at age 55 years will have around twice the 5-year risk of cervical cancer at age 70 to 85 years compared with a woman who continued screening with typical screening adherence."

The authors also compared 5-year and remaining lifetime cervical cancer risks among women with a cervix who stopped screening at a given age after a negative cytology test, a negative HPV test, or a negative co-test with cytology and HPV.

A 70-year old woman whose screening history was unknown had an average remaining lifetime risk of 1 in 588.

Her remaining lifetime risk at age 70 years was reduced to 1 in 1206 if she had a negative cytology test, 1 in 6525 if she had a negative HPV test, and 1 in 9550 if she had a negative co-test for cytology and HPV.

In conclusion, for women with a cervix, the benefits of cytology screening for cervical cancer persist until about age 75 years, "although these incremental benefits decline with age," Malagon and colleagues observe.

"A single negative HPV test provides strong reassurance against future risk of cervical cancer in older women exiting screening, as women negative for oncogenic HPV after age 55 years were predicted to be at low risk of cervical cancer for the rest of their lives."