The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test

Abstract

Background The cobas® HPV Test (“cobas”, Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for 1) ASC-US triage to determine need for colposcopy, 2) combined screening with cytology (“co-testing”), and 3) primary HPV screening. Methods To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared to those of an established method, the LINEAR ARRAY HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+. Results Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the kappa statistic for agreement between cobas and LA was 0.86 (95%CI=0.86-0.87). In all 3 scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women aged 21 and older with ASC-US (14.5%, 95%CI=13.5%-15.5% versus 3.5%, 95%CI=3.3%-3.6%); women aged 30 and older that were HPV-positive cytology-negative (10.3%, 95%CI=9.6%-11.1% versus 2.3%, 95%CI=2.2%-2.4%); and all women 25 and older that were HPV-positive (18.5%, 95%CI=17.8%-19.2% versus 4.3%, 95%CI=4.2%-4.4%). Conclusion The cobas and LA results show excellent agreement. The data support HPV16 typing. Impact HPV16 typing is useful in the management of HPV- positive/cytology-negative women in co-testing, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US.

Quality assurance of human papillomavirus (HPV) testing in the implementation of HPV primary screening in Norway: an inter-laboratory reproducibility study

“…Still, categorizing the genotypes based on the cobas HPV Test results, may be of interest as it has been suggested that HPV16 and/or HPV18 positive women should have a more aggressive follow-up regime compared to women positive for the HR-HPV category [9]. In the present data, discordant results related to genotypes were observed for nine samples.…”

Epidemiological study of high‑risk human papillomavirus infection in subjects with abnormal cytological findings in cervical cancer screening

“…Analysis of European and North American cases indicated that the sensitivity rate is only 53%, giving rise to a new era of molecular testing for HPV DNA (24). In May 2003, the US FDA approved the joint application of TCT and HPV-DNA HC2 testing for the primary screening of women aged ≥30 years (17). In 2005, the World Health Organization's International Agency for Research on Cancer (IARC) recommended HR-HPV testing for use in the primary screening of cervical cancer (22).…”

Determinants of High-Risk Human Papillomavirus Seroprevalence and DNA Prevalence in Mid-Adult Women

“…9 (These types are included in commercially-available HPV DNA assays for routine cervical cancer screening [some commercially available assays also include HPV-66, a possibly carcinogenic type that we did not evaluate by serology].) Fifteen percent of the women in our cohort had detectable hrHPV DNA in self-collected vaginal samples (comparable to hrHPV prevalence in cervical samples from similarly aged women undergoing routine cervical cancer screening 19 ), and an additional 56% had evidence of prior hrHPV infection through positive serology. While comparisons across populations are complicated by differences in populations studied and serology assays used (including number of hrHPV types targeted), we compared our seroprevalence estimates for individual types HPV-16 and HPV-18 to U.S. national data among similar-aged women, 20 and noted that our estimates were higher (25% versus 17%–22% for HPV-16 and 14% versus 7%–10% for HPV-18).…”