The article reviews the epidemiology of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNC), highlighting recent data on incidence trends, the global HPV-attributable fraction, sex disparities in risk, the latency period between infection and cancer, the potential impact of prophylactic HPV vaccination, and prospects for secondary prevention through screening. HPV is established as the primary cause of an increase in OPC incidence, particularly among men, in various geographic regions. The article discusses the increasing prevalence of HPV-positive OPC, the role of sexual behavior in HPV transmission, and the challenges in developing effective screening methods. Prophylactic HPV vaccines are effective in preventing HPV infections and associated precancerous lesions, but their impact on OPC incidence is less clear. The article emphasizes the need for further epidemiological studies and clinical trials to develop and evaluate strategies for secondary prevention and early detection of HPV-positive OPC.The article reviews the epidemiology of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNC), highlighting recent data on incidence trends, the global HPV-attributable fraction, sex disparities in risk, the latency period between infection and cancer, the potential impact of prophylactic HPV vaccination, and prospects for secondary prevention through screening. HPV is established as the primary cause of an increase in OPC incidence, particularly among men, in various geographic regions. The article discusses the increasing prevalence of HPV-positive OPC, the role of sexual behavior in HPV transmission, and the challenges in developing effective screening methods. Prophylactic HPV vaccines are effective in preventing HPV infections and associated precancerous lesions, but their impact on OPC incidence is less clear. The article emphasizes the need for further epidemiological studies and clinical trials to develop and evaluate strategies for secondary prevention and early detection of HPV-positive OPC.