Introduction: The HIV epidemic in Latin America is concentrated among men who have sex with men (MSM) and transgender women (TGW) with transmission predominately occurring during unprotected anal intercourse. This mode of transmission is also responsible for other sexually transmitted infections (STIs) such as herpes simplex, chlamydia and gonorrhoea, human papillomavirus (HPV)/genital warts and syphilis. Studies assessing the prevalence of HIV and HPV among MSM have not addressed the role of genital warts and HPV-related diseases in the acquisition of HIV infection. Community-based testing programmes are a potentially important way to remove barriers including stigma for individuals to learn about their STI status. Methods and analysis: The prospective cohort study will recruit 600 MSM/TGW at a community centre in Lima, Peru, named Epicentro. Half of the participants will have a history of or have current anogenital warts (AGW), and the other half will have no history of AGW. We will measure the prevalence and acquisition of STIs including syphilis, HPV, chlamydia and gonorrhoea and the HIV-incidence in the two groups. To the best of our knowledge, it will be the first study that specifically examines the impact of genital warts on incident HIV infection. This study will help to understand the relationship between AGW and HIV infection among MSM/TGW in Peru. Furthermore, it may facilitate the development of preventive intervention strategies to reduce the prevalence of AGW and prevent incident HIV infection. HPV-related manifestations may be a good proxy for HIV risk. Ethics and dissemination: This study was approved by institutional review boards at the University of California, Los Angeles (UCLA) in the USA and Impacta in Peru. Study findings will be shared with the Peruvian Ministry of Health as well as other international and national public health organisations. Study results will be translated into Spanish for participants. Trial registration number: The Clinicaltrials.gov registration number is NCT01387412.