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

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.