By Lori Solomon, Editor, Diagnostic Testing & Emerging Technologies
DNA-based human papillomavirus tests can be used as a primary screening tool for cervical cancer in women 25 years of age and older, according to a controversial interim guidance published online Jan. 7 and in the February issue of Obstetrics & Gynecology. This clinical guidance further signals a shift away from annual Pap smears to detect cervical cancer, although some clinicians are still leery of forgoing Pap smears altogether, favoring a cotesting strategy instead.
While high-risk HPV (hrHPV) testing was first addressed in the 2011 cervical cancer screening guidelines, which recommended cotesting, the latest expert panel says the growing body of evidence clearly favors primary hrHPV testing over cytology. Calling primary hrHPV testing “an important scientific and clinical advance,” the authors say hrHPV has the potential to further reduce cervical cancer-associated morbidity and mortality in the United States. The test’s benefits, they say, come from its high sensitivity, which can improve cancer and precancerous detection over Pap smears.
The interim guidance panel consisted of 13 experts, representing the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology. The group reviewed published literature and data from the registration study for Roche Diagnostics’ cobas HPV test. The U.S. Food and Drug Administration approved the test for primary screening back in April 2014, although the agency did not include specific recommendations for applying hrHPV screening.
The panel’s interim clinical guidelines include:
- A negative hrHPV test conveys a significantly lower 3-year risk of cervical cancer (grade 3+), compared to negative cytology results.
- Following negative primary hrHPV test results, screening should occur “no sooner” than every 3 years. Recognizing that screening intervals are still a source of ongoing debate, the panel says there is currently “insufficient prospective U.S. data to recommend screening intervals beyond three years.”
- The group lowered the age of initiation of hrHPV testing to 25 years, while acknowledging concerns about the test’s specificity. The potential harms from using hrHPV in a population with higher prevalence of temporary HPV infections include the stress and anxiety resulting from expensive and invasive follow-up for false-positives and treatment of non-neoplastic HPV lesions.
- Genotyping for HPV 16 and 18 can be used to triage hrHPV-positive women, with reflex cytology for the 12 other hrHPV genotypes. The authors call this a “reasonable approach to managing hrHPV-positive women” offering “an appropriate balance between safety and test utilization.”
“As with all new advances that enter clinical practice, the introduction of primary hrHPV screening raises a number of questions and concerns,” writes lead author Warner Hug, M.D., from the University of Alabama, Birmingham. “Despite the improved sensitivity associated with primary hrHPV testing compared with cytology, clinicians should be aware that false negative results will continue to occur.”
Despite their certainty over the clear benefits of hrHPV, the authors say that additional studies are needed including comparative effectiveness studies that examine projected lifetime number of screening tests and direct cost comparisons of primary hrHPV screening to cytology and cotesting.
Several authors report financial ties to the diagnostics industry.