Clinical, Genomic, and Metagenomic Characterization of Oral Tongue Squamous Cell Carcinoma in Patients Who Do Not Smoke

Head Neck. 2015 Nov;37(11):1642-9. doi: 10.1002/hed.23807. Epub 2014 Aug 23.

Abstract

Background: Evidence suggests the incidence of oral tongue squamous cell carcinoma is increasing in young patients, many who have no history of tobacco use.

Methods: We clinically reviewed 89 patients with oral tongue cancer. Exomic sequencing of tumor DNA from 6 nonsmokers was performed and compared to previously sequenced cases. RNA from 20 tumors was evaluated by massively parallel sequencing to search for potentially oncogenic viruses.

Results: Non-smokers (53 of 89) were younger than smokers (36 of 89; mean, 50.4 vs 61.9 years; p < .001), and seemed more likely to be women (58.5% vs 38.9%; p = .069). Nonsmokers had fewer TP53 mutations (p = .02) than smokers. No tumor-associated viruses were detected.

Conclusion: The young age of nonsmoking patients with oral tongue cancer and fewer TP53 mutations suggest a viral role in this disease. Our efforts to identify such a virus were unsuccessful. Further studies are warranted to elucidate the drivers of carcinogenesis in these patients.

Keywords: head and neck cancer; next-generation sequencing; nonsmokers; oral tongue; squamous cell carcinoma.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cohort Studies
  • DNA, Neoplasm / genetics*
  • Databases, Factual
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genomics
  • Humans
  • Incidence
  • Male
  • Metagenome / genetics
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Smoking
  • Tongue Neoplasms / epidemiology
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • DNA, Neoplasm
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53