The role of human papillomavirus in the pathogenesis of oropharyngeal squamous cell carcinoma and the impact of vaccination on disease prevention: a narrative review
Muonga Chiyokoma Kabaso, Mahati Iyyappan, Rahma Islam, Deethya Balamurali, Shogo Tajima, Ellie McDougall, Zunair RahmanAbstract
Objective
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.
Methods
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.
Results
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.
Conclusion
Gender-neutral vaccination, improved uptake and the development of therapeutic vaccines and phosphoinositide 3 kinase-targeted therapies offer realistic strategies to reduce disease burden.