Traditional cytology-based screening programs for cervical cancer prevention have failed everywhere other than resource-abundant settings. In resource constrained settings, while tests such as visual inspection with acetic acid (VIA) provide a suitable platform for clinical evaluation and are very cheap, they are highly rater-dependent and suffer from substantial false positivity. Carcinogenic HPV DNA detection (e.g., HPV DNA testing by Hybrid Capture-2 [hc2] assay) is less specific than cytology and cannot differentiate between the great majority of benign infections and the few persistent infections linked to cervical pre-cancer. A reliable and robust test that improves both the sensitivity and specificity of screening may provide better alternatives for HIV-infected women than conventional cytology screening or VIA.
This study (funded through the NIH Office of AIDS Research‘Intramural-to-India’ initiative) will be conducted in collaboration with the National AIDS Research Institute, a permanent institute of the Indian Council of Medical Research in Pune, India. A cohort of 1,000 HIV-infected women will undergo evaluation using two novel and potentially sustainable, lower-cost tests for accurate screening for cervical cancer. These tests include detection of HPV E6 oncoprotein (using a low-cost, rapid, strip test that detects HPV E6 oncoprotein and can be performed without complex machinery or a cold chain) and immunocytochemical staining using p16INK4a/Ki-67 (a biomarker correlated with the oncogenic transformation of cervical cells following persistent carcinogenic HPV infection). This study involves simultaneous and independent evaluation of these novel biomarkers along with confirmation by colposcopy/histopathology for all participants. Linear Array HPV polymerase chain reaction assay will measure carcinogenic HPV-DNA for comparison purposes. This observational study will permit investigators to describe the sensitivity and specificity of any of the tests or combinations with reasonable precision for a wide range of prevalence of cervical pre-cancer and cancer. This study will allow evaluation of the field adoption and efficacy of these newer assays as well as permit validation of collection, transport, storage, and evaluation protocols.