Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women

Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade‐off of being less specific. We investigated whether select combinations of HPV genotypes, ascertained by Linear Array (LA) and Xpert HPV (GX), can optimize sensitivity/specificity trade‐offs to detect high‐grade cervical intraepithelial neoplasia (CIN2+). In a study in Cape Town, South Africa, 586 women living without and 535 living with HIV, aged 30‐65 years, were recruited. Each woman underwent a pelvic exam to collect cervical samples (tested by LA and GX for 14 high‐risk HPV genotypes) and underwent colposcopy with histological sampling to determine CIN2+. In multivariable logistic regression of LA results, only HPV genotypes 16, 18, 31, 33, 35, 52, 58 were significantly associated with CIN2+ (P < .05). Xpert includes these seven types along with HPV 45 within three of the test's five channels and we defined these eight types as restricted genotyping (ie 16, 18, 31, 33, 35, 45, 52, 58). Full genotyping was defined as all 14 high‐risk types. Sensitivity estimates for full genotyping using LA were similar to that of restricted genotyping: 83.9% (full) vs 79.0% (restricted) in women without HIV and 93.0% (full) vs 88.9% (restricted) in women living with HIV. Specificity estimates improved for restricted vs full genotyping: 87.4% (full) vs 90.8% (restricted) in women without HIV and 63.7% (full) vs 71.4% (restricted) in women living with HIV. To optimize the performance of HPV testing for cervical cancer screening in high‐burden, under‐resourced settings like South Africa, only HPV 16, 18, 31, 33, 35, 45, 52, 58 could be included to define screen‐positive. We recommend the inclusion of HPV45 for its known link to adenocarcinoma.