Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor-response rates and survival outcomes. However, in some geographic regions, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV-related OPSCC. Methods: We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy in a tertiary Cancer Center in Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease-specific survival and recurrencefree survival were calculated. Results: One hundred twenty-seven (59.1%) patients were diagnosed with HPVpositive OPSCC. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided in 104 (48.4%, P = .69) patients. Overall, the 5-year cancer-specific survival was 73.5% and 68.1% for patients positive and negative to HPV, respectively. Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (P = .68). While all distant relapses were found to be lung metastases in the HPV-negative group, we observed unusual sites of distant metastases in the HPV-positive group. Conclusions: HPV status was not associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPVpositive tumors were more likely than patients with HPV-negative OPSCC to have unusual distant metastases.