Introduction Human papillomavirus (HPV) infection is transmitted through skin-to-skin contact, and vaginal and anal sex are the most common transmission routes. Sex workers and men who have sex with men (MSM) are more exposed to the virus, and therefore, a higher frequency of this infection would be expected. The prevalence of HPV infection types and the forms and factors of transmission must be investigated to control infection-related outcomes. This protocol study will be the first nationwide study with a uniform methodology to evaluate HPV prevalence of and infection types among sex workers and MSM in Brazil.

Methods and analysis This multicentre cross-sectional study will be conducted with a respondent-driven sampling method to recruit 1174 sex workers and 1198 MSM from all regions of Brazil. The study will consist of preliminary interviews to verify the eligibility criteria and characterise the network size as well as a second questionnaire to obtain sociodemographic, behavioural and sexual information. Specimens from the oral cavity and anal and cervical or penile/scrotal sites will be collected. All HPV samples will be processed in a certified central laboratory. Other sexually transmitted infections will be evaluated by interview and by rapid testing for HIV and syphilis. Strict quality control will be conducted using different procedures, including the training and certification of the health professionals responsible for acquiring data and monitoring visits.

Ethics and dissemination The project was approved by the research ethics committee of the main institution and the corresponding ethics committees of the recruitment sites. Due to the literature gap on the sexual health of sex workers and MSM and the intense stigma surrounding these populations, a critical analysis of the study results will contribute to epidemiological knowledge and will be useful for the development of strategies against virus morbidities.