The US Food and Drug Administration recently approved the use of a human papillomavirus (HPV) test as a primary cervical cancer screening test in women as young as 25 years, yet physicians are unlikely to ditch the Papanicolaou (Pap) test soon, experts say.
Roche’s cobas test is 1 of 4 HPV tests on the market, but thus far it is the only one approved for primary screening, rather than for use in conjunction with Pap tests.
The cobas test was initially approved in April 2011 for women aged 21 to 29 years who had an abnormal Pap test and as a “co-test” with the Pap test for women aged 30 to 65 years. The test detects DNA from HPV 16 and HPV 18, the 2 types of HPV that cause 70% of cervical cancer cases worldwide, as well as for DNA from 12 other high-risk types of HPV.
If the cobas test is used as a primary screen, those who test positive for HPV 16 or HPV 18 are supposed to have a colposcopy, according to the FDA. If they test positive for 1 of the other high-risk HPV types, they are supposed to have a Pap test to determine whether they need colposcopy.
“I don’t know that we’re going to see an immediate change in how patients are screened for cervical cancer,” Levi Downs, MD, a spokesman for the Society of Gynecologic Oncology and an associate professor of obstetrics and gynecology at the University of Minnesota School of Medicine, Minneapolis, said to Medscape Medical News.
“We have such a good test now,” Dr. Downs said, referring to the Pap test, which physicians first began using in the 1940s. “We know that it has dramatically changed the impact of cervical cancer. Physicians, I think, are going to take their time in deciding what the data (about primary screening with an HPV test) mean.”
Despite its approval, critical questions remain unanswered about the HPV test as a primary screening tool for cervical cancer, David Chelmow, MD, chair of obstetrics and gynecology at Virginia Commonwealth University in Richmond, told Medscape Medical News. For example, should women be screened more frequently or less frequently than current guidelines recommend for the Pap test? How should women aged 25 through 29 years be screened, given that the FDA approved cobas as a primary HPV test for those as young as 25 years, but current guidelines advise against routine use of an HPV test in women younger than 30 years? In addition, researchers do not yet know whether primary screening with the cobas test will lead to an increase in colposcopy and cervical biopsies compared with Pap screening.
Guidelines, Community Need Time to Catch Up
Even though the FDA has approved the cobas test as a solo screening tool, physicians should not scramble to begin using it as such because of the questions that remain, according to Warner Huh, MD, a gynecologic oncologist at the University of Alabama at Birmingham.
Dr. Huh chairs a panel convened by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology that has been working for months to develop interim guidance on primary HPV testing for cervical cancer screening. The guidance has not yet been released.
Until such guidance is available, Dr. Huh said physicians should stick with what they know works. “I would encourage that women get screened based on the current guidelines,” he told Medscape Medical News.
“I do believe that doctors will continue to co-test regularly in the foreseeable future. I don’t anticipate any major changes in screening practices in the near future,” he continued.
The most recent cervical cancer screening guidelines came out in 2012. The US Preventive Services Task Force issued 1 set, and the American Cancer Society, the American Society of Colposcopy and Cervical Pathology, and the American Society of Clinical Pathology issued the other set.
Although not exactly the same, the 2 sets of guidelines are similar, and neither includes the option of using an HPV test as a primary screening tool. Rather, both say HPV testing should be used in conjunction with a Pap test, and then only in women aged 30 to 65 years. Those women with normal results on both tests can wait 5 years until they are screened again. In contrast, women aged 21 to 29 years, an age group in which HPV infection is relatively common but nearly always clears spontaneously, should be screened every 3 years with a Pap test alone, which is also an option for women aged 30 to 65 years. In this younger age group, HPV testing should be reserved for women who have an abnormal Pap.
Interim guidance may not be the answer, according to Karen Smith-McCune, MD, PhD. “There will be areas of uncertainty…such as how often to do the test,” Dr. Smith-McCune, director of the cervical dysplasia clinic at the University of California, San Francisco, told Medscape Medical News. “Guidelines that leave us with areas of uncertainty are not really helpful.”
Sarah Feldman, MD, MPH, echoes that point. “I’m kind of concerned that the interim guidance may actually confuse things, rather than help things,” Dr. Feldman, who is on the faculty of Harvard Medical School and practices gynecologic oncology at Brigham and Women’s Hospital in Boston, Massachusetts, told Medscape Medical News. In a viewpoint article published online May 5 in JAMA Internal Medicine, she called for simplifying the current screening and management guidelines.
She notes that the trial that provided supportive data for the new cobas test indication was well-designed but lasted only 3 years, so it is not known whether women could wait longer than that between normal screenings. “We may find ourselves in a transition phase where it adds additional confusion,” she says of the new cervical cancer screening option.
“Pap testing has been a successful test,” Dr. Feldman continued. “I think in the future we probably will move to primary HPV testing. But we don’t have enough information yet to make that move.”
Dr. Smith-McCune, who also authored a viewpoint article published in the same issue of JAMA Internal Medicine, even questions the value of HPV testing even as a co-test. “I’m of the opinion that just because something is FDA-approved doesn’t mean it has a role in clinical practice,” she said.
In addition, Dr. Smith-McCune says she does not understand why the 2012 guidelines developed by the American Cancer Society, the American Society of Colposcopy and Cervical Pathology, and the American Society of Clinical Pathology prefer co-testing over the Pap test alone. (The preventive services task force guidelines are neutral on that issue.) “Is more [testing] better, or is more just more? Is it just more confusing? Is it going to prevent cervical cancer or not?” she questioned. “This really is an unanswered question for the co-testing strategy.”
In her viewpoint article, Dr. Smith-McCune notes that overall, 3% to 8% of women screened with co-testing have a normal Pap test with a positive HPV test, and that percentage is even higher in younger women. Although the guidelines from the cancer society, the American Society of Colposcopy and Cervical Pathology, and the American Society of Clinical Pathology prefer co-testing over the Pap test alone, they acknowledge that more research is needed into how to manage women with a normal Pap test and a positive HPV test, Dr. Smith-McCune writes.
However, for some experts, the debate over how best to screen women obscures the fact that a lack of screening, rather than the type of screening, is the main reason US women are still diagnosed with cervical cancer. “We really want to impact the total of women with cervical cancer in this country,” Dr. Chelmow said. “Half of them are women who don’t get screened.”
Dr. Huh serves as an unpaid consultant to Roche and sits on the company’s publication steering committee. Dr. Smith-McCune is the founding chair of the clinical and scientific advisory board for OncoHealth Inc, which is developing diagnostic tests for cervical cancer and other cancers associated with HPV. She also holds stock options in the company. In addition, she is a coinvestigator for 2 studies funded by the National Institutes of Health, related to cervical cancer screening. Dr. Feldman is paid to write chapters for UpToDate, a peer-reviewed online textbook.