Clinical, genomic, and metagenomic characterization of oral tongue squamous cell carcinoma in patients who do not smoke

Ryan Li, Daniel L. Faden, Carole Fakhry, Chaz Langelier, Yuchen Jiao, Yuxuan Wang, Matthew D. Wilkerson, Chandra Sekhar Pedamallu, Matthew Old, James Lang, Myriam Loyo, Sun Mi Ahn, Marietta Tan, Zhen Gooi, Jason Chan, Jeremy Richmon, Laura D. Wood, Ralph H. Hruban, Justin Bishop, William H. WestraChristine H. Chung, Joseph Califano, Christine G. Gourin, Chetan Bettegowda, Matthew Meyerson, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joseph L. Derisi, Wayne M. Koch, Nishant Agrawal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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.

Original languageEnglish
Pages (from-to)1642-1649
Number of pages8
JournalHead and Neck
Issue number11
StatePublished - Nov 2015
Externally publishedYes


  • head and neck cancer
  • next-generation sequencing
  • nonsmokers
  • oral tongue
  • squamous cell carcinoma


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