Improving the Sensitivity-Specificity Balance of Human Papillomavirus Testing on Self- and Clinician-Collected Samples in South Africa.

Abstract

Purpose: Human papillomavirus (HPV) testing on self-collected samples may increase coverage of cervical cancer screening, but previous studies have observed lower specificity of HPV testing in self- versus clinician-collected samples. Here we investigate strategies to improve the sensitivity-specificity balance of a round of HPV testing on self-collected samples.

Materials and methods: Women living with and without HIV, age 30-65 years, were recruited in South Africa. Self-collected vaginal samples and clinician-collected cervical samples were tested with Xpert HPV, an assay that detects the 14 high-risk HPV types in five separate channels: (P1) HPV 16; (P2) HPV 18, 45; (P3) HPV 31, 33, 35, 52, 58; (P4) HPV 51, 59; and (P5) HPV 39, 56, 66, 68. All women underwent colposcopy with histology sampling, and diagnosis of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was determined by adjudicated pathology. The AUC and related performance parameters were calculated using logistic regression with the cycle threshold (Ct) values of the channels as predictors.

Results: HPV prevalence in women without and with HIV was higher in self-collected (25.1% v 61.5%) than in clinician-collected samples (16.2% v 48.4%). The optimal model to predict CIN2+ used Ct values from the three channels that detect HPV 16, 18, 45, 31, 33, 35, 52, and/or 58. AUC was superior for testing on clinician-collected (0.908) than on self-collected samples (0.878; P = .0261) in women without HIV, as well as for women living with HIV (0.868 v 0.819; clinician v self; P = .0002). Alternate approaches to handling multiple types and sequential testing approaches did not allow self-testing to achieve equivalent performance to testing on clinician-collected samples.

Conclusion: Using more stringent Ct cutoffs on the three channels that detect the eight highest-risk HPV types can improve the sensitivity-specificity balance of a round of screening in both self- and clinician-collected samples. Although performance of HPV testing on self-collected samples is excellent, performance parameters are better on clinician-collected samples.