Infection by human papillomavirus (HPV) induces various cancers, mainly cervical cancer but also anal and pharyngeal cancers. Reunion Island is a French department in the Indian Ocean. Due to the history of its settlement, the island's population has a wide variety of origins, and the population's sociodemographic characteristics differ from those of the French mainland. These characteristics make the island's population an original French population in its own right, particularly in terms of health. Cervical cancer incidence and mortality in Reunion Island are 10.4 per 100,000 and 4.4 per 100,000, respectively, both of which are much higher than those in mainland France. There is also a disparity in the prevalence of different HPV types, with types 33 and 52 being overrepresented and type 18 being underrepresented. However, vaccination and screening coverage in Reunion Island is low. It is important to understand the burden of infection and its risk factors in members of the young Reunionese population at risk of HPV infection to promote and evaluate the implementation of future vaccination and screening programs on a larger scale. The RUN-SurV-HPV study will have the following four objectives: (1) to describe the prevalence of HPV genotypes in a population at risk of sexually transmitted infections in Reunion Island; (2) to describe the prevalence of HPV genotypes by anatomical site, gender, and sexuality; (3) to describe the correlates and risk factors for HPV detection; and (4) to examine HPV genotypes between different anatomical sites. Cross-sectional analyses of 1200 routine vaginal, anal, pharyngeal, and urinary samples collected between October 2020 to December 2022 from female and male patients aged 16 to 30 years undergoing Chlamydia trachomatis testing at a sexually transmitted infection (STI) testing center at Reunion Island will be performed. The population included 333 women who all had vaginal and pharyngeal swabs, with 80 of them also having had an anal swab. There are 167 men who have sex with men who have had anal and pharyngeal swabs, and 120 men who have sex with women who have had a urine swab only. Results will be correlated with sociodemographic and clinical data collected routinely during the consultations. HPV detection and genotyping will be performed using the Anyplex II HPV28 detection assay (Seegene). The first polymerase chain reactions should begin in November 2023. The first results should be submitted for publication in 2024. The study will determine HPV prevalence by age, sex, male sexual preference, human immunodeficiency virus status, and STI co-infection. Collecting data from young patients not usually routinely screened for HPV infection will be a simple and reproducible way of better understanding local specificities, encouraging vaccination campaigns in the short-term, and evaluating their effectiveness in the future. DERR1-10.2196/47379.