Vaccines against HPV hold great promise for the long term prevention of cervical cancer & anogenital warts (AGW). Two vaccines targeting the most frequent genotypes involved in the aetiology of cervical cancer (HPV16/18) & AGW (HPV6/11), in bivalent & quadrivalent forms, have been licensed. A nonavalent vaccine covering 90% of cancer types is being evaluated. HPV vaccination programmes typically target young girls. However, the relevance of extending vaccination to other groups, e.g. HIV+ women, is of public health importance since they are at higher risk of HPV infection, persistence & disease progression. Cervical cancer screening programmes can identify HIV+ women in need of CIN management treatment & prevention through vaccination. Although HPV vaccines have been shown to be safe & immunogenic in HIV+ populations in South Africa (SA), data is lacking on their efficacy against CIN & AGW. Our hypothesis is that HPV vaccination can decrease the incidence of HPV-related disease among HIV+ African women. The goal is to determine the likely effectiveness of adding vaccination to an HPV-based screening programme among HIV+ women in SA to inform the design of a phase III/IV individually randomized trial of the effectiveness of vaccination against CIN2+ & AGW endpoints. We will test HPV serology in stored serum samples taken from SA study cohorts that have also measured cervical HPV DNA & CIN prevalence & incidence to examine current & prior exposure to vaccine preventable HPV genotypes. The data will contribute to estimate & model the fraction of vaccine preventable types & the expected vaccine effectiveness with a bi/quadri/nonavalent vaccine against CIN2+, AGW & persistent HPV, & determine key trial parameters (e.g. sample size, trial duration, frequency of visits, eligibility criteria). We will also extend the analysis to predict the effectiveness on cancers prevented among HIV+ women. Qualitative research will determine the feasibility & acceptability of the trial.