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The incidence of oropharyngeal squamous cell carcinoma (SCCa) has increased in the United States despite a decrease in tobacco usage, and it may be driven by an increase in oral human papilloma virus (HPV) infection. We studied the incidence of tongue base and tonsillar SCCa over time to understand the changing epidemiology of oropharyngeal SCCa.Large national tumor registry.We studied patients diagnosed with oropharyngeal SCCa in SEER data (Surveillance, Epidemiology, and End Results) from 1973 to 2009. Age-adjusted incidence rates standardized to the 2000 US population were computed, with stratifications for age, sex, race, and stage.The sample included 10,061 tongue base and 11,515 tonsillar oropharyngeal cancers. When stratified by age, the incidence of oropharyngeal SCCa in patients ≤55 years of age more than doubled over 30 years. While the incidence rate in females remained stable, the rate in males more than doubled, from 2 per 100,000 persons in 1973 to >4 per 100,000 persons in 2009. The age-adjusted incidence of oropharyngeal SCCa in patients of black race/ethnicity remained consistently elevated, but the incidence in patients of white race/ethnicity rose from 1.3 per 100,000 persons to >2.5 per 100,000 persons, surpassing the incidence in black patients starting in 2002.The observation that the incidence of oropharyngeal SCCa is increasing among younger white males, despite a reduction in tobacco usage in the United States, is consistent with HPV as the source. Primary and secondary prevention strategies may be warranted in this population.