Alberto Gutierrez, PhD
The approval followed a unanimous 13-0 vote from the FDA’s Microbiology Devices Panel supporting the claim that the benefits of the test outweighed its risk and that the test was safe and effective. However, this opinion generated concerns among numerous organizations that believed the approval would represent a radical change in the way women are screened for cervical cancer. To address this uncertainty, the Society of Gynecologic Oncology (SGO), which is the largest organization of doctors specializing in the treatment of women’s cancers, announced that interim guidance documents were being developed to help healthcare professionals determine how to best incorporate first-line HPV testing.
“The approval has raised a number of questions about how HPV testing will be used and whether the Pap test will continue to play a role in cervical cancer screening,” SGO wrote in a statement issued following the approval. “Primary HPV testing does not replace the Pap test, and it is extremely unlikely that doctors will stop using the Pap any time soon. FDA approval of primary HPV testing means the HPV test can be used first when screening a woman for cervical cancer.”
The FDA initially approved the cobas HPV test in 2011 as a secondary or adjunctive cervical screening tool to Pap smear. The test, which is a qualitative multiplex assay manufactured by Roche Diagnostics, detects genotype-specific information from 14 high-risk HPV types, including HPV 16 and 18, which is responsible for 70% of all cervical cancers. According to the National Cancer Institute, over 99% of cervical cancer cases are linked to long-term HPV infections.
The first-line approval was based on results from a long-term analysis of the ATHENA study, which demonstrated that the cobas HPV test was significantly more sensitive at detecting cervical intraepithelial neoplasia grade 3 (CIN3) when compared with liquid-based cytology.
In the trial, liquid-based cytology or HPV DNA testing was used to analyze specimens from 41,955 women aged 25 or older. Women with atypical squamous cells of undetermined significance or those with worse cytology underwent colposcopy and diagnostic biopsies. The primary endpoint of the study was histologically confirmed ≥CIN3.
In materials compiled for the advisory panel, the FDA developed a comparison between the cobas HPV Test and cytology alone based on their assessment of the data from the ATHENA trial. In this analysis, the sensitivity for ≥CIN3 was 58.26% (95% CI, 44.02-74.37) for the cobas HPV Test compared with 42.63% (95% CI, 31.75-55.41) for cytology alone.
The positive predictive value for the risk of ≥CIN3 in women referred to colposcopy by the cobas HPV Test was 12.25% (95% CI, 10.69-13.91) compared with 6.47% (95% CI, 5.54-7.50) for cytology alone. The FDA established that the false positive rate for ≥CIN3 was 4.09% (95% CI, 3.89-4.28) for the cobas HPV Test compared with 6.04% (95% CI, 5.81-6.27) for cytology alone.
“Today’s approval offers women and physicians a new option for cervical cancer screening,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a statement. “Roche Diagnostics conducted a well-designed study that provided the FDA with a reasonable assurance of the safety and effectiveness when used as a primary screening tool for cervical cancer.”