The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.