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Distant progression (DP) in oropharyngeal squamous cell carcinoma (OPSCC) has significant impact on morbidity and mortality. This study systematically reviewed the literature on studies reporting location and timing of DP after human papillomavirus (HPV)+ or HPV− OPSCCs. PubMed, EMBASE, and the Cochrane Library were systematically searched for studies reporting DP in patients treated with curative intend for an OPSCC. Outcome was site of and time to DP stratified on HPV‐status. Seven studies (n = 1564; 77% HPV+) were included in which 313 patients (20%) developed a DP (70% HPV+). The most common site of DP was the lungs (n = 232) regardless of HPV‐status. Patients with HPV+ tumors were more prone to dissemination involving multiple sites (risk ratio = 16.49). There was no difference in time to DP when stratified on HPV‐status (P = .10). The pattern of but not time to DP was significantly different in patients with OPSCC when stratified on HPV‐status. [ABSTRACT FROM AUTHOR]