For women of a certain age, the Pap test is a yearly ritual to endure but also a chance to visit with their gynecologist and talk about the other lumps, bumps, and indignities of womanhood. And as uncomfortable as the exam may be, surely the women who have benefited from early detection of cervical cancer are grateful to the test’s inventor, George Papanicolaou, and those who championed his test into a major public health success story of the 20th century. It is credited with cutting the incidence of cervical cancer in half over the past 30 years.
But times change, and the Pap test now finds itself on the verge of irrelevance. Ever since human papilloma virus (HPV) was identified as the culprit behind the vast majority of cervical cancers and an HPV screening exam gained approval in 2009, the spotlight has swiveled away from the Pap test to the HPV test.
The Pap test’s ultimate demise will likely take place when cervical cancer incidence declines as the HPV vaccine takes effect at a population level. The vaccine has been slow to catch on in the United States, but it has the potential to eradicate cervical cancer in coming decades. Look at Australia: Its aggressive HPV vaccine policies have led to 78% of teenage girls getting the vaccine. The 10-year-old program has shown results: Far fewer Australian girls have genital warts and high-grade cervical abnormalities. It will take longer to know what the effect on cervical cancer might be.
Source: Health, United States, 2016, Table 71
Australian health care providers have stopped using the Pap test altogether and now rely on the HPV test as the primary screening tool for cervical cancer. Some experts in the United States see such a change as inevitable, but not until this country has more young people vaccinated. About half of all adolescent girls in the U.S. were vaccinated in 2016, and 38% of boys.
Until more of the population is protected, the conversation among screening experts in the United States is all about which tests are needed at what intervals for which women. A long list of medical societies found themselves largely in consensus the last time they reviewed the evidence in 2012:
In 2017, the U.S. Preventive Services Task Force took a fresh look at the evidence for cervical cancer screening and lobbed a bomb into the kumbaya circle of consensus. Women and their doctors could safely choose either the Pap or the HPV test, the USPSTF said in a draft recommendation. Notably, the task force rejected the idea of testing with both the Pap and HPV test, which is the preferred option in the medical society guidelines. For the first time, a major U.S. public health organization was suggesting the Pap could be ignored.
While the difference might seem subtle, it was significant enough that it was criticized by some screening experts and triggered some strong pushback from some women’s health groups.
The dissenting experts don’t believe this country is ready to rely on primary HPV testing to keep its population free of cervical cancer lesions. While head-to-head studies comparing the two tests generally find the HPV is a more sensitive test and identifies more women who are found to have lesions, the Pap tests’s lower rate of false positives provides an alternative for women who don’t want to take the risk of unnecessary treatment.
Doing both tests at the same time—co-testing—has seemed a safe way to hedge both bets, but the task force said it found evidence that co-testing results in too many false positives, resulting in unnecessary colposcopies, and chose not to recommend it. That was countered by a trio of prominent cytopathologists in a commentary in the Journal of the American Society of Cytopathology. They noted that cervical cancer screening in the U.S. tends to be “opportunistic” without reliable follow-up, and that the ATHENA clinical trial found no difference in colposcopy procedures between HPV testing alone and co-testing with the Pap test.
Meanwhile, evidence continues to be produced about how the tests perform in real life. A study of 1.2 million Kaiser Permanente patients in Northern California published in the Journal of the National Cancer Institute in November 2017 found the HPV test portion of the co-test accounted for the vast majority of its effectiveness. “The added sensitivity of co-testing vs. HPV alone for detection of treatable cancer affected extremely few women,” the authors concluded.
Experts expect that eventually the HPV test will win out as the primary screening tool, but they question whether that time is now. “I don’t think it’s a wrong change,” says screening expert Warner Huh, MD, professor of obstetrics and gynecology at the University of Alabama–Birmingham. “It’s a bit fast, considering that just recently in 2013 we finally recognized co-testing as an A-level recommendation and we started getting everyone on board adding HPV.”
“We know in this country and in Central and South America cervical cancer is a huge problem, [and women of color] get it at a much higher rate,” says Carolyn Adigé, president of the Prevent Cancer Foundation.
Meanwhile, some women’s health groups are uncomfortable with the idea of stepping away from the tried-and-true Pap test. They say HPV does not identify all women with cervical lesions, and they argue that the research supporting HPV testing is largely conducted in Europe among cohorts that included few women of color and used different HPV tests than are currently in use. “We know in this country and in Central and South America cervical cancer is a huge problem, they get it at a much higher rate,” says Carolyn Aldigé, president of the Prevent Cancer Foundation. “Women of color were not taken into consideration.”
Black women in the United States have higher rates of Pap testing but still experience the highest mortality rate from cervical cancer. Researchers have cited limited access to treatment and cultural barriers as some potential reasons, but Aldigé suggested the difference could be at a biological level.
Huh disagrees, arguing that the theory that women of color may have a different risk profile for cervical cancer is unproven. He notes that the USPSTF guideline is meant to cover most people and individuals in subgroups are free to use other testing regimens if they like.
As for the idea that HPV testing alone might miss some women with cancers, he asks what the alternative would be. “There’s no evidence the Pap would pick up those patients either,” he says.
The Pap continues to offer some value in catching the small percent of lesions that aren’t HPV related, argues David Chelmow, MD, professor of obstetrics and gynecology at Virginia Commonwealth University. But as the number of cervical cancers presumably goes down with vaccination, the Pap’s findings become less statistically valid, he says.
As with all medical guidelines, there is a gap between what policymakers do up in the clouds at the population level and what women and their doctors will choose to do in the exam room. Gynecologists are likely to make a choice based on the preferences of the women in front of them. The physician might explain that the HPV is a great screening tool but also results in some false positives, so the patient might end up getting a colposcopy and maybe a cervical biopsy with its attendant risks.
“I don’t think it’s wrong that the patient should have a voice in that process,” Huh says. “That’s a major gap in how we address the recommendations.” On the other hand, sticking with the old-school, yearly Pap isn’t the answer either, Huh and others say, though they regularly see patients whose doctors are happy to continue the tradition (and insurers who will pay for it). The potential risk is that the Pap would pick up transient lesions that would resolve on their own, which is why they are recommended every three years.
Beyond the initial screening, the policy must also take into account how a positive result is managed.
Debbie Saslow, who directs women’s cancer issues for the American Cancer Society, is concerned that following a positive HPV test, more women will be sent for colposcopies than need them. That balance can be difficult. The individual woman may want to risk overtreatment to catch a potential cancer, but she may not be aware of the potential risks of colposcopy, such as infection and weakening of the cervix, with potential implications for a future pregnancy. “Do we know one cancer detected earlier is worth how many thousands of women having false positives?” asks Saslow. “What is the tradeoff? We don’t know.”
Medical societies and task forces write the guidelines, but insurers and their reimbursement policies have a major influence on how closely those guidelines are followed. Insurers don’t seem to have waded very far into the Pap–HPV debate. The HPV test tends to be a little more expensive than the Pap test (about $40 vs. about $30), so putting aside issues of false positives and additional testing, the difference isn’t huge.
Huh figures it hasn’t been worth the manpower for insurers to review women’s annual exams and deny an unnecessary annual Pap, but at some point when guidelines are more closely tied to payment, it may become more important to insurers. “A lot of insurers are five years behind and struggling to catch up,” he says.
Since the ACA’s passage, insurers have been limited in their women’s preventive-health policymaking because they are required to cover services that are recommended by the USPSTF with no copays. Cathryn Donaldson, a spokesperson for America’s Health Insurance Plans, says plans would follow preventive-care coverage requirements and pay for any additional screening recommended by the clinician.
Anecdotally, Huh and others say they routinely see women whose doctors are giving them yearly Pap tests, just as they have for decades. Presumably, their insurers are picking up the tab. Until insurers start saying no to the Pap test, the HPV test may have difficulty getting accepted. Huh sees HPV testing as taking over someday, but 2018 may be a little too soon: “Screening changes in this country don’t happen overnight.” Saslow worries that if the final USPSTF recommendation leaves out co-testing, then insurers may not cover it. “The task force has been very research-oriented,” she says. “They are less likely to take into account the practical issues as the professional organizations are.”