PURPOSE We evaluated whether cancer biomarkers improve the performance of Xpert human papillomavirus (HPV) testing as screening for cervical intraepithelial neoplasia grade 2 or greater (CIN2+). METHODS In a clinical study in Cape Town, South Africa, 418 HIV-negative and 426 HIV-positive women, age 30 to 65 years, were recruited. All women had cervical samples collected and underwent colposcopy and histologic sampling with consensus pathology review. Cervical samples were tested onsite using Xpert HPV, which detects 14 high-risk HPV types in 5 channels: HPV 16; HPV 18 and -45; HPV 31, -33, -35, -52, and -58; HPV 51 and -59; and HPV 39, -56, -66, and -68. Cycle threshold (Ct) values are outputted for each channel. Samples were also tested using real-time polymerase chain reaction to detect mRNA for CDKN2A, TOP2A, and MKi-67. Results were reported as ΔCt values relative to internal controls. Logistic regression and receiver operating characteristic curves were used to evaluate associations between Ct values for HPV and biomarkers with CIN2+. RESULTS Ct values from channels detecting HPV 16, -18, -45, -33, -35, -52, and -58 were informative to predict CIN2+. Area under the curve was 0.906 in HIV-negative and 0.870 in HIV-positive women. When sensitivity was set at 80%, specificity was 94.0% in HIV-negative and 82.7% in HIV-positive women. ΔCt values for detection of mRNA for CDKN2A and MKi-67 added significant improvement to the prediction of CIN2+ when included with the Ct values from the 3 informative Xpert channels. Including both HPV and biomarker parameters, area under the curve was 0.944 in HIV-negative and 0.913 in HIV-positive women. When sensitivity was set at 80%, specificity was 97.3% in HIV-negative and 89.6% in HIV-positive women. CONCLUSION Improvements in specificity of a round of screening using Xpert HPV can be achieved with the addition of cancer biomarkers.
Residual Disease and HPV Persistence after Cryotherapy for Cervical Intraepithelial Neoplasia Grade 2/3 in HIV-Positive Women in Kenya
