Molecular and epidemiological data now support an etiologic role for oncogenic human papillomavirus (HPV) in oral cancers in women and men. Recent studies have demonstrated an increase in the incidence of HPV-associated oral cancers in the United States. Moreover, the incidence rates for these cancers are higher in men than women. Oral HPV infections acquired through oral sex appear to be the principal risk factor for HPV-associated oral cancers. Despite reports in the popular press that the prevalence of oral sexual behaviors is increasing in the adolescent population, trends in these behaviors over time are largely unavailable. However, data indicate that oral–genital contact is frequently practiced among adolescents; adolescents do not typically consider this a risky behavior. The majority of oral cancers (approximately 90%) caused by HPV are identified as HPV 16 positive. Therefore, HPV-associated oral cancers could be prevented by a prophylactic vaccine if the vaccine were demonstrated to be capable of preventing oral HPV 16 infection. These findings have created new potential opportunities for the primary prevention of oral cancers.