Human papillomavirus (HPV) infection is the principal cause of a distinct form of oropharyngeal squamous cell carcinoma that is increasing in incidence among men in the United States. Human papillomavirus–positive oropharyngeal squamous cell carcinomas (OSCCs) are associated with sexual behavior in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. At least 90% of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV type 16 (HPV-16), and oral infection confers an approximate 50-fold increase in risk for HPVpositive OSCC. The incidence of OSCC has significantly increased over the last 3 decades in several countries, and HPV has been directly implicated as the underlying cause. Although the incidence of HPV-negative OSCC declined by 50% in the United States from 1988 to 2004 (from 2.0 cases per 100 000 population to 1.0 per 100 000), the incidence of HPV-positive OSCC increased by 225% (from 0.8 per 100 000 to 2.6 per 100 000), predominantly among young individuals, men, and white individuals. The increase among the young is consistent with reported sexual behavioral changes by birth cohort since the 1950s in the United States.
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