Substantial increases in oropharyngeal squamous cell carcinoma (OPSCC) incidence have been observed across the developed world and attributed to the rising influence of the Human papillomavirus (HPV) on disease aetiology. This pan-UK multicentre, cross-sectional study aimed to accurately determine the proportion of HPV-positive and -negative OPSCC within the United Kingdom population. Archival tumour-tissue blocks from 1602 patients, previously diagnosed with OPSCC (2002-2011), were collated from eleven centres. HPV status was determined using three validated commercial tests, providing valid data for 1474 cases. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of OPSCC caused by HPV between 2002-2011 was 51.8% (95% CI:49.3, 54.4) and this remained unchanged throughout the decade (unadjusted risk ratio:1.00 (95% CI:0.99, 1.02). However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase (age standardised rate (ASR) 2002:2.1 (95% CI:1.9, 2.2); 2011:4.1(95% CI:4.0, 4.3)). Although the absolute numbers of OPSCC diagnosed within the UK between 2002 and 2011 almost doubled, the proportion of HPV-attributable cases remained static, at approximately 50%. These results provide the first evidence that, in the UK, the rapidly increasing incidence of OPSCC cannot be solely attributable to the influence of HPV. The reasons for this previously undetected parallel increase in HPV-positive and -negative disease warrants further investigation so that appropriate future prevention strategies for both HPV-positive and -negative disease can be implemented.