News for Your Practice
FDA Advisory Committee recommends HPV test as primary screening tool for cervical cancer
The cobas® HPV test could replace the Pap smear for cervical cancer screening
Advances in cervical cancer screening continue apace. We are fortunate that these advances are based on a substantial amount of high-quality prospective evidence. Many of these advances are designed to target the women who have clinically relevant disease while minimizing harm and anxiety caused by unnecessary procedures related to cervical screening test abnormalities that have little clinical relevance.
With clinicians being regularly judged on performance and outcomes, adoption of advances and new guidelines should be considered relatively quickly by women’s health providers.
In this article, I focus on two significant advances of the past (and coming) year:
- recent application and unanimous approval by a Food and Drug Administration (FDA) expert panel for the use of the cobas human papillomavirus (HPV) DNA test as a primary cervical cancer screen
- the latest update of guidelines on the management of abnormal cervical screening tests from the American Society for Colposcopy and Cervical Pathology (ASCCP).
cobas HPV TEST IS POISED FOR FDA APPROVAL AS A PRIMARY SCREEN FOR CERVICAL CANCER
Wright TC Jr, Stoler MH, Behrens CM, Apple R, Derion T, Wright TL. The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol. 2012;206(1):46.e1–e11.
An FDA expert panel unanimously approved the cobas (Roche Molecular Diagnostics; Pleasanton, California) HPV DNA test on March 12, 2014. The FDA will decide on potential approval within the coming months. Although the FDA sometimes reaches a different decision from one of its advisory committees when it comes to a final vote on a product or device, most often the FDA concurs with the committee’s judgment. Therefore, approval of the cobas HPV test as a primary screen is likely.
Related article: FDA Advisory Committee recommends HPV test as primary screening tool for cervical cancer Deborah Reale (News for your Practice, March 2014)
The cobas HPV test yields a pooled result for 12 high-risk HPV types (hrHPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), as well as individual results for types 16 and 18; it also has an internal control for specimen adequacy. HPV 16 and 18 account for roughly 70% of all cases of cervical cancer, and infection with both types are known to place women at high risk for having clinically relevant disease—more so than the other hrHPV types.
COMMITTEE REVIEWED DATA FROM ATHENA IN VOTING FOR APPROVAL
In considering the cobas HPV test, the advisory committee reviewed data from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) trial, a prospective, multicenter, US-based study of 47,208 women aged 21 and older. These women were recruited at the time of undergoing routine screening for cervical cancer; only 2.6% had been vaccinated against HPV. All were screened by liquid-based cytology and an HPV test. Those who had abnormal cytology or a positive test for a high-risk HPV type underwent colposcopy, as did a randomly selected group of women aged 25 or older who tested negative on both tests.
The prevalence of abnormal findings was:
- 7.1% for liquid-based cytology
- 12.6% for pooled high-risk HPV
- 2.8% for HPV 16
- 1.0% for HPV 18.
As expected, cytologic abnormalities and infection with high-risk HPV types declined with increasing age. The adjusted prevalence of cervical intraepithelial neoplasia (CIN) grade 2 or higher in women aged 25 to 34 years was 2.3%; it declined to 1.5% among women older than age 34. Of note, approximately 500,000 US women are given a diagnosis of CIN 2 or CIN 3 each year in the United States.
WHY ATHENA IS IMPORTANT
This US-based trial was designed to assess the medical utility of pooled high-risk HPV DNA in addition to genotyping for HPV 16 and 18 in three populations:
- women aged 21 and older with a cytologic finding of atypical squamous cells of undetermined significance (ASC-US)
- women aged 30 and older with normal cytology
- women aged 25 and older in the overall screening population with any cytologic finding.
Investigators were particularly interested in the use of the HPV test as:
- a triage for women with abnormal cytologic findings
- an adjunct to guide clinical management of women with negative cytology results
- a potential front-line test in the screening of women aged 25 and older.
Related article: Endometrial cancer update: The move toward personalized cancer care Lindsay M. Kuroki, MD, and David G. Mutch, MD (October 2013)
The participants of the ATHENA trial were representative of women undergoing screening for cervical cancer in the United States—both in terms of demographics and in the distribution of cytologic findings. For example, recent US census data indicate that the female population is 79% white, 13% black, and 16% Hispanic or Latino—figures comparable to the breakdown of race/ethnicity in the ATHENA trial.
