Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis

Int J Cancer. 2024 Mar 1;154(5):830-841. doi: 10.1002/ijc.34763. Epub 2023 Oct 20.

Abstract

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.

Keywords: attributable fraction (AF); human papillomavirus (HPV); oropharyngeal; squamous cell carcinoma (SCC).

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Squamous Cell* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Head and Neck Neoplasms*
  • Human Papillomavirus Viruses
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / metabolism
  • Humans
  • Oropharyngeal Neoplasms*
  • Papillomaviridae / genetics
  • Papillomaviridae / metabolism
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / metabolism
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • CDKN2A protein, human