Abstract Background: There is evidence of an interaction between HIV and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status. Methods: A total of 1,320 women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub-sample of histology) and HPV DNA testing were performed at approximately 4-month intervals yielding data from over 7,900 clinic visits. Competing risk modeling was used to estimate rates for transitioning between three clinically relevant natural history stages: Normal, HPV, and HSIL (high-grade squamous intraepithelial lesions). Among HIV-positive women, exploratory univariate analyses were conducted examining the impact of HPV type, infection with multiple HPV types, HIV type, CD4+ count, and age. Results: HIV-positive women had higher rates of progression and lower rates of regression compared with HIV-negative women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence interval (CI), 1.69–3.86; P < 0.0001] times higher rate of progression from HPV to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07, respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count <200/mm3 were associated with adverse transitions. Conclusions: Adverse HIV effects persist throughout HPV natural history stages. Impact: In the limited-resource setting of sub-Saharan Africa where cervical cancer screening is not widely available, the high-risk population of HIV-positive women may be ideal for targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886–94. ©2017 AACR.