Oropharyngeal squamous cell carcinoma accounts for over a third of head and neck cancers, with the cost of treatment in the UK reaching £14.3 billion over 15 years. Human papillomavirus (HPV) has surpassed smoking and alcohol as the leading aetiological driver. This review examines HPV pathogenesis and the impact of vaccination on disease prevention.

PubMed, Embase and Medline were searched for articles published to December 2025, combining terms including oropharyngeal, squamous cell carcinoma, HPV, vaccines, pathogenesis and phosphoinositide 3 kinase. Gynaecological HPV malignancies were excluded, and reference lists were hand-searched.

Human papillomavirus 16 E6 and E7 oncoproteins degrade p53 and retinoblastoma protein, dysregulate phosphoinositide 3 kinase, protein kinase B and mechanistic target of rapamycin signalling and drive genomic instability. p16 is a useful but imperfect surrogate biomarker. Vaccination reduces oral HPV prevalence and is projected to lower incidence, although uptake remains suboptimal among males and in deprived areas.

Gender-neutral vaccination, improved uptake and the development of therapeutic vaccines and phosphoinositide 3 kinase-targeted therapies offer realistic strategies to reduce disease burden.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) has favourable oncological outcomes, supporting the use of transoral robotic surgery with risk-adapted adjuvant therapy. While anticipated adjuvant treatment intensity is informed by pre-operative assessment, definitive post-operative histopathology determines final risk stratification.

A single-centre study was conducted at University College London Hospitals of 44 HPV-positive oropharyngeal SCC patients treated with primary transoral robotic surgery and selective neck dissection. Discrepancies between clinical and pathological staging, and their impact on adjuvant treatment recommendations, were assessed.

Staging discrepancies were identified in 38 per cent of patients. Pathological nodal upstaging occurred in 20.5 per cent of patients, commonly caused by higher-than-anticipated nodal burden. Involved surgical margins were present in 70.5 per cent of patients. Overall, definitive histopathology resulted in escalation of anticipated adjuvant treatment intensity in 61 per cent of patients, with 52 per cent reclassified as high-risk disease.

Post-operative histopathology frequently altered anticipated risk stratification, highlighting the limitations of pre-operative staging and the clinical impact of a surgical-first approach.