The VASCAR (viral testing alone with Pap triage for screening cervical cancer in routine practice) study was a single-center demonstration project initiated in Montreal, Canada in 2011 among more than 23,000 women attending routine cervical cancer screening. In a secondary phase of VASCAR, we determined genotype-specific risks of disease progression to biopsy-confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) associated with HPV types 16, 18, and/or the other 12 (pooled) high-risk types, compared to Pap cytology. We also assessed the diagnostic performance of HPV genotyping compared to cytological triage.
Women aged 30-65 were originally screened for HPV using the Hybrid Capture® 2 (HC2) Test. Women with positive results were triaged using conventional cytology, and those with positive Pap cytology results (≥ASC-US; atypical squamous cells of undetermined significance) were referred to colposcopy. We retrospectively genotyped 1396 cervical specimens that were HPV+ with HC2 using the Roche’s cobas® 4800 HPV system, and extracted the women’s medical history. We evaluated diagnostic performance of triage tests in the first year of follow-up among women positive for: (1) HPV16; (2) HPV18; (3) HPV16 and/or HPV18 and; (4) one or more of the other 12 HPV types. Using hierarchical and exclusive categories of HPV positivity (any HPV16; else HPV18; else 12 other HPVs), we correlated HPV status at enrollment with detection of histologically confirmed CIN2+ by estimating hazards ratios (HR) with 95% confidence intervals (CI) using Cox proportional hazards regression.
Of the 1396 women, 1092 (78%) were classified as normal, 136 (10%) had CIN1, 80 (6%) had CIN2, 81 (6%) had CIN3 and 7 women had cancer, throughout the entire follow-up period. Sensitivity of HPVs 16, 18, 16 and/or 18, and any high-risk HPV for prevalent CIN2+ (n=76) were 35.5% (CI:24.9-47.3), 9.2% (CI:3.8-18.1), 43.4% (CI:32.1-55.3), and 64.5% (CI:52.7-75.1), respectively. Conversely, cytology triage (ASC-US+) had a sensitivity of 92.0% (CI:83.4-97.0). Corresponding specificity values were 84.0% (CI:81.9-86.0), 95.0% (CI:93.7-96.1), 79.7% (CI:77.4-81.8), 33.4% (CI:30.9-36.0), and 73.6 (CI:71.1-76.0). Compared to cobas HPV- and HC2 HPV+ women, the HRs were 7.3 (CI:3.8-14.3), 3.9 (CI:1.5-10.2), and 2.7 (CI:1.4-5.2) for women with any HPV16, HPV18, and 12 other types, respectively. Compared to women with normal cytology, the HRs for AS-CUS, LSIL, and HSIL (SIL: squamous intraepithelial lesion) were 3.7 (CI:2.5-5.7), 5.0 (CI:3.1-8.0) and 16.5 (CI:11.0-24.7), respectively.
Cytology and genotyping seem to be comparable in triaging women with positive HPV results on screening.