Extended Genotyping as Triage of HPV Positive Screened Women in Low-and-Middle Income Countries.

Cervical cancer screening coverage in low- and middle-income countries is low, and many screened women are lost to follow-up. Point-of-care testing that allows same-day treatment could reduce the incidence of this cancer, but same-day triage testing is required to prevent overtreatment and minimise loss-to-follow-up before treatment. Built-in extended genotyping with the Xpert® human papilloma virus (HPV) assay offers point-of-care triage, but treatment thresholds differ. We calculated test performance of the Xpert® HPV assay for HIV-positive and HIV-negative women. Extended HPV-genotyping was evaluated against histology and missing values were imputed to correct for verification bias. We report test performance at different thresholds, namely Top3 (HPV16, 18, 45), Top8 (HPV16, 18, 45, 31, 33, 35, 52, 58) and Top14 (HPV16, 18, 45, 31, 33, 35, 52, 58, 51, 59, 39, 56, 66, 68) hierarchical viral types. Included were 1063 participants, aged 25-65 years, mean age 41.2 years; 42.7% were HIV-positive. HIV-positive women were significantly more likely to test positive on multiple test channels and were more likely to have histology proven disease. Screening only for Top3, sensitivity (CIN3+) was 31.3%/41.5%, and specificity (CIN2+) 97.0%/95.6% for HIV-negative/HIV-positive women respectively. Top8 rendered results of 57.8%/76.4% and 91.8%/84.6% respectively, which is acceptable for a triage test. Treatment at the threshold of Top8 types requires less than three referrals among all HIV-groups for one case of histology proven disease. Results confirmed screening for all 14 high-risk HPV types is most sensitive but necessitates triage. Extended genotyping using a threshold of Top8 oncogenic types rendered best balance of sensitivity and specificity and overall test performance for both HIV-groups in a test-and-treat strategy. CLINICAL TRIAL REGISTRATION: The study was registered as Trial ID NCT02956031 on ClinicalTrials. gov.