Louise Kuhn

Performance of thermoablation among women treated for high‐risk human papillomavirus in a screen‐and‐treat program in South Africa

AbstractThermal ablation is a simple treatment option for HPV‐associated, pre‐cancerous disease, has a low risk of complications and can be undertaken by non‐specialists. For these reasons, it is one of the recommended treatment modalities for cervical cancer screening programs. As part of a screen‐and‐treat demonstration study, 3060 women living with and without HIV, aged 30–65 years, were recruited at an urban site in South Africa. HPV testing stratified the population into those at highest risk for precancerous disease, identifying 529 (17.3%) women with high HPV viral loads on select HPV genotypes and multi‐channel infections indicating their need for treatment. Among this group, visual assessment criteria further stratified this at‐risk population into those suitable versus unsuitable for ablative therapy. 483 (91.3%) of 529 women met visual criteria defining their suitability for ablative treatment and all were treated with thermoablation. Women were followed at 6‐ and 12‐months where HPV testing and colposcopy with histological sampling were performed. HPV persistence at 12 months despite treatment was 51.8%, and detection of histologically confirmed cervical intraepithelial neoplasia grade 2 or higher occurred in 24.0%. Being HIV‐positive, older age, multi‐channel infection, high HPV viral load, and low CD4 count were associated with these indicators of treatment failure. Cervical cancer screening programs that target treatment to the highest risk women are likely to observe higher indicators of treatment failure than less focused programs. Although thermoablation is an approved treatment modality, our results highlight the urgency of finding more effective but safe and practical treatment options for precancerous disease.

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

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.