The cobas HPV Test was approved in 2014 by the FDA as a primary tool for cervical cancer screening in women â‰¥25 years of age, highlighting the need for updated guidelines to direct the use of approved screening methods in clinical practice.
The cobas HPV Test was approved in 2014 by the US Food and Drug Administration (FDA) as a primary tool for cervical cancer screening in women ≥25 years of age, highlighting the need for updated guidelines to direct the use of approved screening methods in clinical practice.
Genital infection with human papillomavirus (HPV) is responsible for nearly all cases of cervical cancer. HPV16 and 18, the most oncogenic genotypes, cause over 70% of cases.
While the prevalence of cervical cancer has dramatically declined since the inception of Papanicolaou (Pap) testing, approximately 12,000 new cases of invasive disease are still predicted each year in the United States. With the US Centers for Disease Control and Prevention estimating nearly 14 million new HPV infections annually, effective screening methods remain a priority.
In conventional Pap testing, cytopathology is used to detect cervical intraepithelial neoplasia (CIN) as an indicator of precancerous changes in the cervix. Liquid-based cytology, where collected cells are first preserved in fixative, is also FDA-approved (ThinPrep [Hologic, Inc.] and SurePath [TriPath Imaging, Inc.]).
Unfortunately, cytology-based methods may miss high-grade cervical disease in as many as 1 in 10 women with HPV16/18.1As a result, HPV testing was developed to detect viral DNA or RNA in a cervical sample, often before cellular abnormalities are present.
Several HPV tests have been approved by the FDA for use as an adjunct to cytology. First in 2003, the Hybrid Capture 2 assay (QIAGEN/Digene) screens for 13 high-risk and 5 low-risk types, but does not discriminate between specific genotype(s).
Hologic followed with 2 additional DNA-based tests, approved in 2009: Cervista HPV HR, which detects a pool of 14 high-risk variants, and Cervista HPV16/18, specific to the most oncogenic genotypes.
In 2011, the APTIMA HPV Assay (Hologic Gen-Probe Inc.) became the first approved test that detects viral E6/E7 mRNA from 14 pooled, high-risk types.
Roche has a series of HPV DNA tests as well, including Amplicor, Linear Array, and the cobas HPV Test. The latter received FDA approval in 2011 and combines specific identification of HPV16 and 18 with a distinct pool of 12 other high-risk types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68).
In the 3-year prospective ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial,2Roche’s tests were compared with liquid cytology in over 47,000 US women age 21 and older.
According to the ATHENA researchers, the ideal cervical cancer screening approach “would provide maximum sensitivity to minimize missing disease as well as maximum specificity to minimize false-positive results and overreferral.”2
The trial centered on various screening strategies, including cytology alone, HPV with genotyping, cotesting, HPV with reflex cytology, and HPV with genotyping and reflex cytology.
Findings indicated that HPV testing with HPV16/18 genotyping followed by reflex cytology was the best screening algorithm for achieving optimal sensitivity and efficiency. While slightly increasing the rate of colposcopy, this approach greatly reduced the number of screening tests required compared with cotesting options.
At 3-year follow-up, the risk of lesions ≥cervical intraepithelial neoplasia 3 (CIN3) was reduced in patients receiving a negative HPV test versus negative cytology, confirming its safety as a primary test and offering confidence in extended screening intervals.
Notably, 28% of ≥CIN3 disease occurred in women between the ages of 25 to 29, where over 57% of cases were overlooked when screened by cytology alone.3
Largely fueled by the ATHENA findings, the FDA recently approved the cobas HPV Test as a primary screening tool for women at or above the age of 25. This makes cobas the first FDA-approved, stand-alone alternative to cytology.
“Today’s approval offers women and physicians a new option for cervical cancer screening,” noted Alberto Gutierrez, PhD, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health, in a written release.4
The announcement was met with mixed reviews, as opponents expressed concern over the potential for higher costs and over-treatment, especially considering that over 90% of HPV infections naturally resolve within 2 years.
The FDA stressed that their decision merely supports the safety and efficacy of this method, but does not mandate its use.
“Approval of the HPV test does not change current screening recommendations for cervical cancer,” stated the Society of Gynecologic Oncology (SGO).5The SGO is currently collaborating on an “interim guidance” document to aid clinicians until formal guiding principles are released.
The latest update in guidelines for cervical cancer screening came in 2012, jointly issued by the US Preventive Services Task Force, American Cancer Society, American Society for Colposcopy and Cervical Pathology, and the American Society of Clinical Pathologists.
Guidelines recommend Pap testing every 3 years for women between the ages of 21 to 30 years. From age 30 to 65 years, women also have the option of cotesting for cytology and HPV every 5 years. A positive HPV screen can be followed by genotyping for HPV16/18, with subsequent referral for colposcopy when necessary.
For now, practitioners await a new set of guidelines to be issued, anticipating that conventional Pap testing will not be replaced “any time soon.”5
“Although Pap tests have had a tremendous impact on cervical cancer prevention,” the SGO noted, “having one more way to test for cervical cancer…will allow us to do a better job of saving lives and keeping women healthy.”5