Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer

Abstract

High-risk human papillomavirus (HR-HPV) testing is increasingly important. We therefore examined the impact on accuracy of repeated versus one-time testing, type-specific versus pooled detection, and assay analytic sensitivity. By using a nested case-control design from the ASCUS-LSIL Triage Study, we selected women with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n = 325) and a random sample of women with <CIN2 as controls (n = 401). HPV DNA status was assessed using hybrid capture 2 (HC2), a pooled test for 13 HR-HPV types, and the linear array (LA) and the line blot assay (LBA), two PCR-based HPV genotyping assays, at enrollment and the 6-month follow-up visit. The relative sensitivity and specificity for different permutations of multiple measurements were compared to a single measurement using marginal regression models. We found that repeat detection of any HR-HPV (by HC2, LA, or LBA) and of type-specific persistence (by LA or LBA) were significantly more specific but less sensitive than use of a single time point measurement of any HR-HPV. Sensitivity decreased and specificity increased further when testing intervals were increased from 12 to 24 months. Including detection of borderline carcinogenic/noncarcinogenic HPV types with HR-HPV types decreased specificity for repeat measures of HPV with no impact on sensitivity. Similar patterns were observed when we used a CIN3 end point. We conclude that assay performance for detecting incident CIN2/3 was affected by which types were included, the analytic sensitivity of the assay, and the testing interval. These trade-offs need to be considered when assessing the potential overall clinical utility of repeated testing for HR-HPV DNA to identify women at risk for CIN2/3.

Fig 1

(a) Sensitivity for CIN2/3 and false positivity rate (1 − specificity) for the following measurements: single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes by HC2; single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes by LA; 12-month or 24-month detection of type-specific persistent HR-HPV by LA; single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes or HPV types (53, 66, 67, 70, 73, 82, and 82v) by LA (LA∗); and 12-month or 24-month detection of type-specific persistent HR-HPV or HPV types (53, 66, 67, 70, 73, 82, and 82v) by LA (LA∗). (b) Sensitivity for CIN3 and false positivity rate (1 − specificity) for the following measurements: single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes by HC2; single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes by LA; 12-month or 24-month detection of type-specific persistent HR-HPV by LA; single baseline, 12-month repeat detection, or 24-month detection of HR-HPV genotypes or HPV types (53, 66, 67, 70, 73, 82, and 82v) by LA (LA∗); 12-month or 24-month detection of type-specific persistent HR-HPV or HPV types (53, 66, 67, 70, 73, 82, and 82v) by LA (LA∗).