Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

Abstract

In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

“…In addition, no women with benign biopsies had positive HPV 16/18 on Aptima genotyping and no high-grade squamous intraepithelial lesions or worse on biopsy were detected in women with negative HPV 16/18 on Aptima genotyping, which offered superior sensitivity and specificity for high-grade squamous intraepithelial lesions or worse. The findings were consistent with previous studies performed in both screening21 and referral populations 22 23…”

Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

“…Although the follow-up with repeated testing was incomplete, it was very similar to that observed in the randomized controlled trials comparing HPV-based to cytology-based primary cervical screening (14). Nevertheless, a somewhat higher number of high-grade CIN would plausibly be detected with a more complete follow-up (6). …”

“…The study design was described in detail previously (5–11). In short, consecutive routine SurePath samples from 5,034 women arriving at the Department of Pathology of Copenhagen University Hospital Hvidovre in June to August 2011 were collected and tested with liquid-based cytology (LBC; reported using the Bethesda 2001 system) and the four HPV assays (this constituted the baseline testing).…”

“…95%) and moderately complete (ca. 60%) for women with cytology-normal/HPV-positive test results (6). …”

HPV Prevalence in the Dutch cervical cancer screening population (DuSC study): HPV testing using automated HC2, cobas and Aptima workflows

“…In the ATHENA trial, when excluding patients <30 years, overall hrHPV prevalence found was 8.4% (10.5% including women 25–29 years) [12]. In women from the Danish cervical cancer screening program, the hrHPV prevalence was even higher: 9.4% for Aptima, 11.7% for HC2 and 16.2% for cobas [18]. As earlier described, the hrHPV prevalences found in our study with the 3 different testing solutions were in the same range, although the hrHPV prevalence found by the Aptima assay was found to differ significantly when compared to HC2 (7.5% vs 8.5%, respectively; p-value 0.007).…”