HPV and oropharyngeal cancer

Stated that the rising incidence of human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (particularly in the UK, North America, and northern Europe) is driven by changing sexual behaviours, including increased oral sexual exposure (1,2):

• HPV is a double-stranded DNA virus with predilection for squamous epithelium
• squamous cell carcinoma (oropharyngeal squamous cell carcinoma (OPSCC)) is the most common malignancy affecting the oropharynx, specifically the lymphoid tissue of the palatine tonsils and base of the tongue
  • with respect to OPSCC, there is a causal association between HPV, particularly the HPV 16 subtype compared with HPV negative disease, patients tend to be younger men (1)
    • cryptic epithelium overlying the tonsils and tongue base acts as a reservoir for HPV, providing access to its basal layer for viral replication (2)
      • over time, malignant transformation can occur when viral oncoproteins disrupt tumor suppression genes in native tissue
    • of the >100 HPV known subtypes, HPV 16 and 18 account for most of the HPV related malignancies (oropharyngeal, cervical, anal, and genital cancers)
    • HPV 16 causes up to 96% of HPV related oropharyngeal cancer and about 50% of cervical cancers worldwide
    • HPV-positive OPSCC patients tend to be younger with a median age of diagnosis of 54 years, less exposure to tobacco and alcohol, and higher socioeconomic status and education (3)
      • HPV positivity is less frequent in blacks than in Caucasians (4% in blacks vs. 34% in whites), with a three fold higher incidence in males than females
    • over 90% of oral HPV is sexually transmitted
      • 85% of infections clear within one year.
      • clearance is influenced by several factors, such as age, immune function, smoking status, and viral load
  • HPV associated OPSCC accounts for more than 50% of OPSCC cases in the UK
  • in the UK, the incidence rate of OPSCC in men increased from 3.7 per 100 000 in 2000, to 12 per 100 000 in 2022 (1)
• presentation is often with a painless neck lump due to early nodal metastasis; the primary tumour is usually small and located in the tonsil or the base of the tongue
  • in HPV-related OPSCC, the most common presenting symptom is a neck mass, while those with HPV-negative OPSCC are more likely to complain of a sore throat and dysphagia (2)
  • 2/3 of patients with HPV positive OPSCC present with a painless cervical nodal mass (1)
    • bilateral cervical nodal involvement is possible in midline tumours at the base of the tongue
• prognosis is good and response to treatment is favourable, although standard treatment regimens can result in substantial long term morbidity
• universal HPV vaccination is expected to reduce future incidence; education on the risks and consequences of HPV transmission, particularly by oral sexual contact, is important

Reference:

1. McKenna D, Mayne R, Carson C, Collins S, Reddy E. HPV positive oropharyngeal cancerBMJ 2025; 391 :e086142.
2. Timbang MR, Sim MW, Bewley AF, Farwell DG, Mantravadi A, Moore MG. HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection. Hum Vaccin Immunother. 2019;15(7-8):1920-1928.
3. Elrefaey S, Massaro MA, Chiocca S, Chiesa F, Ansarin M. HPV in oropharyngeal cancer: the basics to know in clinical practice. Acta Otorhinolaryngol Ital. 2014 Oct;34(5):299-309.