NCI is engaged in a collaborative research study to evaluate methods to improve cervical cancer prevention options for human immunodeficiency virus (HIV)-infected women in India. This study is funded through the NIH Office of AIDS Research and the Indian Council of Medical Research’s ‘Intramural-to-India’ initiative. The goals of the study are to evaluate the clinical performance of two novel human papillomavirus (HPV)-based biomarker assays for cervical cancer screening in HIV-infected women. These biomarker assays include (i) immunocytostaining with p16/Ki-67 (biomarkers correlated with the oncogenic transformation of cervical cells following persistent carcinogenic HPV infection), and (ii) testing for HPV E6/E7 mRNA (expressed during progression of a transient to a transforming HPV infection). A cohort of 1,000 HIV-infected women who are attending cervical cancer screening clinics linked to HIV care and treatment centers in three cities (Pune, Chennai, and Belgaum) will be recruited in this clinic-based observational study. Women will undergo simultaneous and independent evaluation by the two novel biomarkers as well as HPV DNA genotyping, liquid cytology, and diagnostic colposcopy with multiple biopsies of acetowhite lesions. This study will permit validation of collection, transport, storage, and implementation protocols; allow evaluation of the field adoption and efficacy of these newer assays; describe sensitivity and specificity of individual tests or test combinations with reasonable precision for a wide range of prevalence of cervical precancer and cancer; and provide a resource for studies of HIV-HPV coinfection.