Objectives/Hypothesis: To document the increasing incidence of oropharyngeal (OP) cancer and to provide evidence that this increase is caused by oncogenic human papilloma virus (HPV).

Study Design: Epidemiologic review and retrospective case series analysis.

Methods: We collected data from Colorado and the United States comparing the average annual age‐adjusted incidence rates of OP and non‐OP head and neck cancer between the periods 1980 to 1990 and 1991 to 2001. We obtained data on 72 patients with OP cancer from a single county in Colorado, from 1980 through 2004. HPV status was determined by DNA‐polymerase chain reaction. We assessed disease‐specific survival.

Results: The average annual age‐adjusted incidence of OP cancer in males in Colorado increased from 2.54 per 100,000 to 3.47 (P < .05) or 36.6%, whereas the U.S. rate increased from 4.34 to 4.81 (P < .05) or 10.8%. The rates in females and the rates of non‐OP head and neck cancer decreased. Of the 72 cases, 50 (69%) were positive for HPV subtype 16. The ratio of HPV‐positive to HPV‐negative cases prior to 1995 was 0.72 (8:11) but was 3.81 (42:11) afterward. Survival was positively affected by HPV status (hazard ratio of 0.15, confidence intervals 0.07–0.36, P < .001). Disease‐specific survival was 83% in the HPV‐positive patients and 15% in the HPV‐negative group.

Conclusions: OP cancer incidence is increasing in Colorado males and to a lesser extent in U.S. males. The HPV‐positive OP cancer cases were more frequent in the later years of the study. Disease‐specific survival was much better in the HPV‐positive patients, confirming that HPV testing defines a unique subset of patients. These findings suggest that HPV oncogenesis accounts for the increase in average annual age‐adjusted incidence of OP cancer.