HPV vaccine development and clinical research have focused on women from the general population and little is known about HPV among indigent women, many of whom experience repeated risk for sexually transmitted infections that continues through the span of their lives. The impact of repeated exposure to HPV, as well as the impact of co-infections like HIV, HCV, gonorrhea, and Chlamydia, on the natural history of HPV infection and HPV-associated disease, is unclear in this population. Moreover, the prevalence of HPV subtypes in this population is unknown, which precludes estimates of potential vaccine effectiveness. A better understanding of HPV among indigent US women could have implications for improvement in health care delivery, particularly regarding HPV vaccine uptake and effectiveness. We propose an exploratory study to assess the prevalence and variability of cervical HPV and cervical HPV disease (cervical intraepithelial neoplasia); associations with co-infections (i.e., HIV, HCV, gonorrhea and Chlamydia) and drug use (e.g., tobacco and crack cocaine); and the feasibility of a larger randomized study among homeless and marginally housed women. Individuals will be recruited from homeless shelters, free food programs and low-income single room occupancy hotels. In this way, study participants will not be limited to individuals who visit specific institutions, thus facilitating reliable estimates from a community-based sample. To the best of our knowledge, this is the first study regarding HPV and HPV disease among homeless and marginally housed women. Ascertaining prevalence and risk factors specific to this population will facilitate a better understanding of HPV among indigent US women, which could have implications for improvement in health care delivery, particularly regarding HPV vaccine uptake and effectiveness. Given that poor and marginally housed women use health services infrequently, the potential benefits of a prophylactic vaccine are of the utmost importance.