Background: Incidence of Oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing as a result of Human Papillomavirus (HPV), genotype 16 infection. Existing treatments for HPV+ OPSCC have high survival rates but often result in significant long-term toxicities, particularly affecting swallowing function, impacting on quality of life (QoL). PATHOS is a UK phase II-III randomized, multi-centre study. Patients undergo Transoral Surgery (Transoral Laser Microsurgery or Transoral Robotic Surgery) prior to post-operative stratification, according to pathological risk factors. Aim: To determine whether reducing intensity of adjuvant treatment; by lowering radiotherapy (RT) dose or, in patients with positive margins and/or Extracapsular Spread (ECS), omitting concurrent chemotherapy, will result in better long-term swallowing function whilst maintaining high Overall Survival rates. Methods: Patients are eligible if requiring primary resection and neck dissection, fit for surgery/treatment, histologically confirmed OPSCC (TNM T1-T3, N0-N2b), and ≥ 18 years. Following informed consent, patients are confirmed as HPV+. Baseline swallowing panel (including QoL) is carried out prior to surgery and during follow-up. Post-op group allocation: Clinical trial information: NCT02215265 PATHOS has recruited 152 patients across 18 UK sites to date, clearly demonstrating feasibility of recruitment. PATHOS will proceed to an international Phase III in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) subject to funding being awarded. Funded by Cancer Research UK (A17161). Coordinated by the Centre for Trials Research, Cardiff University.