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

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 oral tongue cancer patients. Exomic sequencing of tumor DNA from 6 non-smokers 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<0.001), and appeared more likely to be female, (58.5% vs. 38.9%, P=0.069). Non-smokers had fewer TP53 mutations (P=0.02) than smokers. No tumor-associated viruses were detected. Conclusions The young age of non-smoker oral tongue cancer patients, 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.

Head and neck squamous cell cancers in the United States are rare and the risk now is higher among white individuals compared with black individuals

“…There were non-significant declines in incidence of nasal cavity and nasopharynx, while cancers of the oral cavity, larynx and hypopharynx are declining significantly. A significant increase in oral cavity cancers was confirmed in younger women, however these cancers remain rare with an unknown etiology driving this trend 24 .…”

Therapeutic Insights from Genomic Studies of Head and Neck Squamous Cell Carcinomas

“…It should be noted that a prior report suggested TERT promoter mutations are enriched in tongue cancers(18). In contrast to lung cancers in which many targetable genomic alterations have been identified specifically in patients who lack exogeneous carcinogen exposure in the form of tobacco, two small studies of HNSCCs arising in HPV-negative individuals with minimal tobacco or alcohol histories did not identify any recurrent kinase alterations(19, 20). …”

The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade

“…Although human papillomavirus (HPV) has been associated with the increasing incidence of oropharyngeal cancer in young men over the past decades [3], it is not involved in oral carcinogenesis [4] and therefore, does not account for the increasing incidence of OTSCC in young women [5]. Moreover, recent studies have not yet identified any other potentially oncogenic virus in oral cavity [6].…”

“…Despite the fact that OSCC arising in NSND and smokers drinkers (SD) are epidemiologically different, recent studies emphasized that they share most common genomic alterations, such as TP53 and FAT1 mutations, as well as similar miRNA expression profiles [6][7][8]. However, while a fraction of HNSCC (7%) may be attributable only to alcohol drinking [9], information in alcohol habits is missing in those studies.…”