Cervical Screening Often Stops at 65, but Should It?

“Did you love your wife?” asks a character in Rose, a book by Martin Cruz Smith.

“No, but she became a fact through perseverance,” the man replied.

Medicine also has such relationships, it seems ― tentative ideas that turned into fact simply by existing long enough.

Age 65 as the cutoff for cervical screening may be one such example. It has existed for 27 years with limited science to back it up. That may soon change with the launch of a $3.3 million study that is being funded by the National Institutes of Health (NIH). The study is intended to provide a more solid foundation for the benefits and harms of cervical screening for women older than 65.

It’s an important issue: 20% of all cervical cancer cases are found in women who are older than 65. Most of these patients have late-stage disease, which can be fatal. In the United States, 35% of cervical cancer deaths occur after age 65. But women in this age group are usually no longer screened for cervical cancer.

Back in 1996, the US Preventive Services Task Force (USPSTF) recommended that for women at average risk with adequate prior screening, cervical screening should stop at the age of 65. This recommendation has been carried forward year after year and has been incorporated into several other guidelines.

For example, current guidelines from the American Cancer Society (ACS), the American College of Obstetricians and Gynecologists, and the USPSTF recommend that cervical screening stop at aged 65 for patients with adequate prior screening.

“Adequate screening” is defined as three consecutive normal Pap tests or two consecutive negative human papillomavirus tests or two consecutive negative co-tests within the prior 10 years, with the most recent screening within 5 years and with no precancerous lesions in the past 25 years.

This all sounds reasonable; however, for most women, medical records aren’t up to the task of providing a clean bill of cervical health over many decades.

Explained Sarah Feldman, MD, an associate professor in obstetrics, gynecology, and reproductive biology at Harvard Medical School: “You know, when a patient says to me at 65, ‘Should I continue screening?’ I say, ‘Do you have all your results?’ And they’ll say, ‘Well, I remember I had a sort of abnormal pap 15 years ago,’ and I say, ‘Alright; well, who knows what that was?’ So I’ll continue screening.”

According to George Sawaya, MD, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, up to 60% of women do not meet the criteria to end screening at age 65. This means that each year in the US, approximately 1.7 million women turn 65 and should, in theory, continue to undergo screening for cervical cancer.

Unfortunately, the evidence base for the harms and benefits of cervical screening after age 65 is almost nonexistent ― at least by the current standards of evidence-based medicine.

“We need to be clear that we don’t really know the appropriateness of the screening after 65,” said Sawaya, “which is ironic, because cervical cancer screening is probably the most commonly implemented cancer screening test in the country because it starts so early and ends so late and it’s applied so frequently.”

Feldman agrees that the age-65 cutoff is “somewhat arbitrary.” She said, “Why don’t they want to consider it continuing past 65? I don’t really understand, I have to be honest with you.”

So what’s the scientific evidence backing up the 27-year-old recommendation?

In 2018, the USPSTF’s cervical-screening guidelines concluded “with moderate certainty that the benefits of screening in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer do not outweigh the potential harms.”

This recommendation was based on a new decision model commissioned by the USPSTF. The model was needed because, as noted by the guidelines’ authors, “None of the screening trials enrolled women older than 65 years, so direct evidence on when to stop screening is not available.”

In 2020, the ACS carried out a fresh literature review and published its own recommendations. The ACS concluded that “the evidence for the effectiveness of screening beyond age 65 is limited, based solely on observational and modeling studies.”

As a result, the ACS assigned a “qualified recommendation” to the age-65 moratorium (defined as “less certainty about the balance of benefits and harms or about patients’ values and preferences”).

Most recently, the 2021 Updated Cervical Cancer Screening Guidelines, published by the American College of Obstetricians and Gynecologists, endorsed the recommendations of the USPSTF.

Sawaya said, “The whole issue about screening over 65 is complicated from a lot of perspectives. We don’t know a lot about the safety. We don’t really know a lot about patients’ perceptions of it. But we do know that there has to be an upper age limit after which screening is just simply imprudent.”

Sawaya acknowledges that there exists a “heck-why-not” attitude toward cervical screening after 65 among some physicians, given that the tests are quick and cheap and could save a life, but he sounds a note of caution.

“It’s like when we used to use old cameras: the film was cheap, but the developing was really expensive,” Sawaya said. “So it’s not necessarily about the tests being cheap, it’s about the cascade of events [that follow].”

Follow-up for cervical cancer can be more hazardous for a postmenopausal patient than for a younger woman, explained Sawaya, because the transformation zone of the cervix may be difficult to see on colposcopy. Instead of a straightforward 5-minute procedure in the doctor’s office, the older patient may need the operating room simply to provide the first biopsy.

In addition, treatments such as cone biopsy, loop excision, or ablation are also more worrying for older women, said Sawaya, “So you start thinking about the risks of anesthesia, you start thinking about the risks of bleeding and infection, etc. And these have not been well described in older people.”

To add to the uncertainty about the merits and risks of hunting out cervical cancer in older women, a lot has changed in women’s health since 1996.

Explained Sawaya, “This stake was put in the ground in 1996,…but since that time, life expectancy has gained 5 years. So a logical person would say, ‘Oh, well, let’s just say it should be 70 now, right?’ [But] can we even use old studies to inform the current cohort of women who are entering this 65-year-and-older age group?”

To answer all these questions, a 5-year, $3.3 million study funded by the NIH through the National Cancer Institute is now underway.

The project, named Comparative Effectiveness Research to Validate and Improve Cervical Cancer Screening (CERVICCS 2), will be led by Sawaya and Michael Silverberg, PhD, associate director of the Behavioral Health, Aging and Infectious Diseases Section of Kaiser Permanente Northern California’s Division of Research.

It’s not possible to conduct a true randomized controlled trial in this field of medicine for ethical reasons, so CERVICCS 2 will emulate a randomized study by following the fate of approximately 280,000 women older than 65 who were long-term members of two large health systems during 2005–2022. The cohort-study design will allow the researchers to track cervical cancer incidence, stage at diagnosis, and cancer mortality and then compare these outcomes to a person’s screening history ― both before and after the crucial age-65 cutoff.

The California study will also look at the downsides of diagnostic procedures and surgical interventions that follow a positive screening result after the age of 65 and the personal experiences of the women involved.

Sawaya and Silverberg’s team will use software that emulates a clinical trial by utilizing observational data to compare the benefits and risks of screening continuation or screening cessation after age 65.

In effect, after 27 years of loyalty to a recommendation supported by low-quality evidence, medicine will finally have a reliable answer to the question, Should we continue to look for cervical cancer in women over 65?

Sawaya concluded: “There’s very few things that are packaged away and thought to be just the truth. And this is why we always have to be vigilant…. And that’s what keeps science so interesting and exciting.”

Sawaya has disclosed no relevant financial relationships. Feldman writes for UpToDate and receives several NIH grants.

Helen Leask, PhD, CPF, is a freelance science journalist and certified facilitator. She has written for the Canadian Broadcasting Corporation and other outlets, and has worked on books for patients, including The Canadian Guide to Prostate Cancer, 2nd Edition. She can be reached on Twitter @leask_helen.

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