Human papilloma virus (HPV) status is a known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). The eighth edition of American Joint Cancer Committee (AJCC) has modified the TNM staging to reflect this. However, subsite as an independent prognostic factor has not been well studied. This study examined the outcomes of a large cohort of 23,297 tonsil-related (TRA) and non-tonsil-related (nTRA) cancers accessed via a US national database. The authors classified tumours originating from base of tongue, lingual tonsil, tonsil fossa and tonsillar pillar as TRA. Tumours originating from the soft palate, uvula, posterior oropharyngeal wall and lateral pharyngeal wall were classified as nTRA. Most patients had early (71% T1-T2) HPV positive (72%) TRA (96%) OPSCC. A number of variables including HPV status and subsite were analysed, with overall survival as the main endpoint. Kaplan Meyer survival estimates suggest that nTRA subsites had significantly poorer survival outcome even when HPV status was taken into consideration. Multivariate analysis confirmed this association. Other factors that influenced overall survival include advanced age, TNM staging, presence of comorbidities and treatment type. These are consistent with findings in the published literature. The authors do not speculate on the reason for survival differences associated with subsite but acknowledge that further studies are necessary, specifically relating to genetic and other markers such as p16 which were not available in this analysis.