SUMMARYMore than 40 types of sexually transmitted human papillomavirus (HPV) infect the oropharyngeal and anogenital mucosa-high-risk types are associated with precancerous and cancerous lesions of the cervix, vagina, vulva, penis, anus, and oropharynx, and low-risk types cause non-malignant disease, such as anogenital warts. Though most HPV infections resolve spontaneously, immunodeficiencies may result in persistent infection and increased risk of HPV-related sequelae. The mechanism by which HPV results in malignant transformation is multifaceted, involving interactions with numerous cellular pathways, the host immune system, and potentially the host microbiome. Vaccination against HPV is highly efficacious in the prevention of infection and related sequelae, and there now exist several approved formulations that protect against both high- and low-risk types. Despite the advent of vaccination, early detection and treatment of cervical and anal precancerous lesions continues to be integral to secondary prevention-molecular HPV testing, cytology, and tissue biopsy allow for triaging of patients, after which appropriate treatment with close follow-up can avert cancer development.