Will the U.S. Food and Drug Administration (FDA’s) recent approval of Roche Molecular System’s cobas HPV (human papillomavirus) test as a first-line, primary screening test for cervical cancer cause Pap (Papanicolaou) test volumes to plummet? Not likely any time soon, according to the experts DTET
spoke to. Roche’s cobas HPV, the first FDA-approved HPV DNA test, provides individual detection of HPV 16 and HPV 18, the two most common types of infection, together responsible for about 70 percent of cervical cancer, as well as pooled detection for 12 other high-risk types. This expanded indication allows for the test to be used instead of Pap testing to screen for cervical cancer in women 25 years old and older. According to the approval, women who test positive for HPV 16 or 18 should have a colposcopy, while women who test positive for one of the other high-risk HPV types should have a Pap test to determine if a colposcopy is needed. This approval conflicts with current professional practice guidelines, which call for the HPV test as a follow-up test for patients aged 21 and older with abnormal cervical cytology and as an adjunct test to Pap in women 30 years and older. Public comments during the time of the FDA review indicated that professional organizations’ opinions are divided about use of HPV as a primary screening test. While acknowledging that HPV has superior sensitivity over Pap (an estimated 90 percent versus 50 percent), Pap testing is widely engrained in clinical practice. According to G2 Intelligence, Pap smears constitute the largest volume of testing in the anatomic pathology sector, accounting for nearly one-quarter of pathology test volume in 2012 (U.S. Clinical Laboratory and Pathology Testing 2013-2015
). “HPV tests are very, very good at detecting disease. It was approved because it is effective,” explains Debra Papa, M.D., an assistant professor of obstetrics and gynecology at the University of Massachusetts Medical School (Worcester). “The dissent is centered around how do we use this tool.” Experts, including those from the U.S. Centers for Disease Control and Prevention, tell DTET
that any changes in practice are unlikely prior to a review of the data by professional organizations. Even then, if incorporated into practice guidelines, adoption will be gradual, with no big changes expected in the next three to five years, Papa says. The unknowns that clinicians are waiting for research and professional societies to address include:
Takeaway: Despite the recent approval of HPV testing as a first-line screen for cervical cancer, Pap testing volumes will not decrease any time soon. Professional organizations will begin considering how to incorporate this approval into practice guidelines and will begin to address many unanswered clinical questions.
- Patient-Focused Factors—Will women object to being screened for a sexually transmitted infection? Are women comfortable with longer screening intervals?
- Physicians’ Habits—If adopted into clinical practice guidelines, will physicians change their behavior in dropping Pap testing and expanding screening intervals to five years? Some research has shown that current guidelines expanding screening intervals have been slow to be implemented.
- Clinical Factors—The American College of Obstetricians and Gynecologists, in its statement to the FDA during the HPV approval process, highlighted four areas of uncertainty that are not yet fully addressed. Is HPV testing appropriate screening in women younger than 25? What is the appropriate interval for repeat testing? What are the criteria for ending screening? How to transition patients previously screened with the Pap smear alone or cotesting?
- Financial Factors—HPV testing is more costly (an estimated three times the difference; $50 Pap versus $150 for viral DNA HPV test). Will both payers and individuals be willing to pay for this difference? Will HPV testing be more cost-effective when considering downstream costs or will the lower specificity create higher follow-up testing, including colposcopy? A forthcoming paper by Warner Huh, M.D., of the University of Alabama Birmingham, will address some of the cost implications of HPV DNA testing.