The scientific agenda of the current proposal is to conduct short- and long-term studies to validate putative biomarkers for cervical cancer detection and risk assessment in clinical settings. The epidemiologic study design for biologic sample and data collection will continue to focus on high-risk populations, but will be expanded to include HIV-positive women, to increase ethnic diversity, and to add women with invasive cervical disease. We propose a two-year longitudinal study design to provide the follow-up needed to assure precision in disease ascertainment and to evaluate biomarker change in response to therapy. The biorepository will be an EDRN shared resource with specimen collection designed for maximum flexibility, permitting testing of DNA, RNA, and protein biomarkers using a wide variety of current and future technologies and assay platforms so that the most promising biomarkers can be rapidly tested and advanced to the next level of validation. Each specimen in the repository will have linked clinical, epidemiologic (EDRN common data elements), and HPV typing data. This biorepository will provide well-characterized specimens for the most promising biomarkers developed in this and other EDRN studies to be quickly and efficiently evaluated and moved through the validation phases. In most studies multiple markers will be examined to determine the most effective combination for sensitive and specific detection.