Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association

J Oral Pathol Med. 2012 Jan;41(1):9-15. doi: 10.1111/j.1600-0714.2011.01046.x. Epub 2011 May 20.

Abstract

Background: Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well-established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas.

Methods: Molecular techniques including in situ hybridization and immunohistochemistry of p16(INK4A) and p53 for evidences of human papillomavirus in tissue micro-arrays were investigated.

Results: Twenty-four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16(INK4A). The majority of cases without the evidence of human papillomavirus were related to p53 over-expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan-Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 (INK4A).

Conclusions: Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus-positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / classification*
  • Alphapapillomavirus / genetics
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • DNA, Viral / analysis
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / genetics
  • Human papillomavirus 11 / isolation & purification
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / isolation & purification
  • Human papillomavirus 31 / isolation & purification
  • Human papillomavirus 6 / isolation & purification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Microarray Analysis
  • Middle Aged
  • Mouth Neoplasms / virology*
  • Neoplasm Staging
  • Papillomavirus Infections / virology*
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • TP53 protein, human
  • Tumor Suppressor Protein p53