Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population

Cancer Sci. 2014 Apr;105(4):409-17. doi: 10.1111/cas.12369. Epub 2014 Mar 30.


We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV-positive than non-oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV-positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus-unrelated HNSCC and virus-related HNSCC consisting of nasopharyngeal and HPV-positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus-unrelated HNSCC. A disruptive mutation was never found in virus-related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus-unrelated HNSCC. Moreover, in virus-unrelated HNSCC, G:C to T:A transversions were more frequent in ever-smokers than in never-smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever-smokers than in never-smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus-related and virus-unrelated subgroups. In virus-related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus-unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.

Keywords: Disruptive mutation; Epstein-Barr virus; head and neck squamous cell carcinoma; human papillomavirus; p53 mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Female
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / virology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Mutation
  • Papillomaviridae / genetics*
  • Population
  • Tumor Suppressor Protein p53 / genetics*


  • TP53 protein, human
  • Tumor Suppressor Protein p53