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Background Incidence of human papillomavirus (HPV)-related oropharyngeal carcinomas is increasing worldwide. The purpose of this study was to report the incidence in our region, and to determine the influence of HPV status on survival among a heavy smoking population. Methods p16 expression was analyzed in 102 patients with stage II to IV treated with chemoradiation. Overall survival (OS), locoregional control, and disease-free survival (DFS) were compared for HPV+ and HPV− status. Results The majority of patients were smokers (86%). p16 positivity was found in 26.7%. Patients who were HPV+ were younger (56 vs 59 years old; p = .052). No differences were observed regarding tumor stage, sex, or smoking between HPV+ and HPV−. Three-year OS was 67.4% for patients who were HPV+ versus 49.7% for HPV− (hazard ratio [HR], 0.55; p = .095). Conclusion Incidence of HPV-related oropharyngeal carcinoma in Spain is similar to that reported in other European countries. In this sample of heavy smokers, we observed a nonsignificant trend for better outcomes in patients who were HPV+. © 2013 Wiley Periodicals, Inc. Head Neck 36: 782–786, 2014