Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin-fixed, paraffin-embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV-16. Greater risk of HPV infection was associated with males (OR = 2.9, 95% CI = 1.0–8.6), a history of oral-genital sex (OR = 4.2, 95% CI = 1.5–11.7), and oropharyngeal tumors (OR = 10.4, 95% CI = 3.5–31.2). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack-year, 95% CI = 0.96–0.99). HPV infected patients had better overall survival (RR = 0.3, 95% CI = 0.1–0.8) than those with HPV-negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease-specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV-negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender-specific, suggesting the need for further study of the interaction between HPV and gender on survival. © 2003 Wiley-Liss, Inc.