Home >> ALL ISSUES >> 2014 Issues >> Put It on the Board

Put It on the Board

image_pdfCreate PDF

Third cervical cancer screening paradigm may be on the way

April 2014—Clinical trial data and a Food and Drug Administration panel’s full-throated endorsement stand to reshape cervical cancer screening practice recommendations in the U.S.

The FDA’s Microbiology Devices Advisory Committee in March voted 13-0 in favor of a new indication for Roche’s Cobas human papillomavirus test that would allow the assay to be used as a primary screen for cervical cancer in women 25 and older. At this article’s deadline, the FDA had not yet acted on the panel’s advice but the agency usually heeds its advisory committees’ recommendations. The Roche test—approved in 2011—uses amplification of target DNA by polymerase chain reaction and nucleic acid hybridization to detect 14 types of high-risk HPV and specifically identify genotypes 16 and 18.

Dr. Nayar

The FDA committee said women who test negative with the Cobas HPV test “should be followed up in accordance with the physician’s assessment of screening and medical history, other risk factors, and professional guidelines.” Women who test positive for 16 or 18 would be referred for colposcopy, while women who test negative for those two but positive for one of the other 12 high-risk HPV types would be evaluated by cervical cytology to determine whether referral for colposcopy is needed.

The panel’s advice was based on the results of a Roche-funded prospective clinical trial that enrolled more than 47,000 American women. The study, dubbed ATHENA, found that the Cobas HPV test had a sensitivity of 58.26 percent in detecting cervical intraepithelial neoplasia, grade three or higher, compared with 43.63 percent sensitivity achieved by cervical cytology. Meanwhile, Pap testing had a false-positive rate of 6.04 percent for CIN 3 or greater, compared with 4.28 percent for the Cobas HPV test.

Roche’s assay “detects more women with disease and requires fewer women without disease to go to colposcopy than cytology alone,” said an executive summary prepared for the FDA panel. That document and other meeting materials are available at http://j.mp/hpvmeet.

In 2012, the American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology, American College of Obstetricians and Gynecologists, and the U.S. Preventive Services Task Force agreed that women ages 21 to 29 should be screened every three years with cervical cytology. Women 30 to 65 years old should be cotested with Pap and HPV testing every five years, or screened every three years with cervical cytology alone, the organizations said (Schiffman M, et al. N Engl J Med. 2013; 369:2324–2331).

Moving away from cytology’s first-line role in cervical cancer screening would help clinicians and laboratorians, says Thomas C. Wright Jr., MD. He helped design the ATHENA trial and is former director of the Division of Gynecologic, Obstetric, and Cytologic Pathology at Columbia University Medical Center. Roche has paid Dr. Wright for his consulting work and he receives honoraria from the company for speaking engagements, he says.

“From a clinical perspective, having a cytology in HPV-negative women really gives you minimal demonstrable benefit,” Dr. Wright tells CAP TODAY. “But it does add complications. You end up with a whole group of cytological abnormalities in women who are HPV-negative, and you have to follow up many of them.”

For labs, using the Cobas HPV test as a first-line screen would reduce medical liability risk related to gynecologic cytology, Dr. Wright predicts. “Those lawsuits can be very expensive,” he says.

The ASCCP and the Society of Gynecologic Oncology have appointed a panel to develop interim guidance on cervical cancer screening based on the ATHENA trial data. The panel—which includes two voting members representing the American Society of Cytopathology (ASC), the ASCP, and the CAP—will issue its advice by this summer, says Warner K. Huh, MD. He is a professor of gynecologic oncology at the University of Alabama at Birmingham and chair of the interim guidance panel.

“We’re not asking for the death of cytology,” Dr. Huh says. “We are saying it should be used differently than the way we’re using it now. . . . We’re not suggesting that primary HPV testing replace current screening paradigms. We’re saying this is a third paradigm that should be considered and that outperforms cytology.”

Dr. Huh and several other experts say there are no data to determine conclusively whether HPV testing alone outperforms cotesting in cervical cancer screening. The ATHENA trial did not put those two screening approaches head to head.

CAP TODAY
X