Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients.

Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, (60%) and (24%) were most frequently mutated, and the most common CNVs were amplifications (9%) and deletions of (5%) and (4%). Significant associations were found for mutation and nodal disease, lymphovascular invasion and extracapsular spread, mutation or deletion with advanced tumour stage, and amplification with perineural invasion and extracapsular spread. mutation, deletion, and amplification were associated with worse survival in univariate analyses ( < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of mutations, amplifications, and deletions ( < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.