We examined the incidence of human papillomavirus (HPV) in intraoral cancers from 64 patients as determined by the highly sensitive technique of "hot start" polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues. Polymerase-chain-reaction-amplified HPV DNA was detected in the carcinomas of 16 patients (25%). The percentage of men in the HPV-positive (HPV+) group was greater than that in the HPV-negative (HPV-) group (86% versus 68%), but the difference was not statistically significant. There was no intraoral site preference for the HPV+ tumors. The mean age of viral-positive and -negative groups was similar (55 versus 53.8 yr). Three of 16 HPV+ patients (19%) had never smoked cigarettes; however, 16% of the HPV- group had also never smoked. Of interest, 38% of patients interviewed had occupation-related exposures that may have contributed to their carcinogenesis, and a disproportionate percentage of these patients (57%) were from the HPV+ group. There were no statistically significant differences between HPV+ and HPV- cases regarding T stage, clinical stage, and tumor differentiation. The disease-free interval did not differ significantly for HPV+ and HPV- patients in total nor when patients were stratified for tumor stage and clinical stage. The only group that showed some difference in outcome was that of the stage III/IV patients with oral cancer. We observed a shorter survival time for the HPV+ patients as compared with the HPV- patients (P = 0.09). We conclude that, in general, HPV is associated with a minority of intraoral cancers and its presence is not predictive of patient outcome.