Background: TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and-unrelated OPSCC based on p16INK4a overexpression (p16þ), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16þ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite. Patients and methods: All 932 patients, treated with curative intent in Stockholm 2000e2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively. Results: Patients with p16þ otherOPSCC had significantly poorer OS compared to patients with p16þ TSCC/BOTSCC (p Z 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16þ otherOPSCC had a significant poorer OS compared to patients with p16þ TSCC/BOTSCC