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

Kendrick Koo,David Wiesenfeld,Tim A Iseli,Dmitri Mouradov,Oliver M Sieber,Michael J Mccullough,Christopher M Angel,Antony W Burgess

doi:10.3390/cancers13051029

Abstract

Simple SummaryA clinically distinct cohort of non-smoking non-drinking patients who develop oral cavity squamous cell carcinomas has been identified, with previous work suggesting that these patients tend to be older, female, and have poor outcomes. Our study characterised tumour molecular alterations in these patients, identifying differences in genomic profiles as compared to patients who smoke and/or drink. Associations between molecular alterations and other clinical and pathological characteristics were also explored.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, TP53 (60%) and CDKN2A (24%) were most frequently mutated, and the most common CNVs were EGFR amplifications (9%) and deletions of BRCA2 (5%) and CDKN2A (4%). Significant associations were found for TP53 mutation and nodal disease, lymphovascular invasion and extracapsular spread, CDKN2A mutation or deletion with advanced tumour stage, and EGFR amplification with perineural invasion and extracapsular spread. PIK3CA mutation, CDKN2A deletion, and EGFR amplification were associated with worse survival in univariate analyses (p < 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 CDKN2A mutations, EGFR amplifications, and BRCA2 deletions (p < 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.

Highlights

Introduction conditions of the Creative CommonsSquamous cell carcinomas of the head and neck (HNSCC) are a heterogeneous group of cancers arising in the upper aerodigestive tract, with oral cavity cancers being the most common
Clinical details of 176 oral cavity SCC (OSCC) patients examined in this study are summarised in Clinicopathologic details and treatment delivery were similar between retrospective patients (n = 103) diagnosed between January 2007 and August 2010 and prospectively recruited patients (n = 73) diagnosed between January 2014 and July 2016
The proportions of non-drinkers and non-smoking non-drinking patients (NSND) patients were higher in the prospective cohort, consistent with the reported trend of reduced alcohol consumption among Australians over this time period [51] (Supplementary Table S2)

Summary

Introduction

Introduction conditions of the Creative CommonsSquamous cell carcinomas of the head and neck (HNSCC) are a heterogeneous group of cancers arising in the upper aerodigestive tract, with oral cavity cancers being the most common. Retrospective audits of OSCC patients at our centre have revealed a larger than expected group of non-smoking (40%) and NSND (24%) patients who are predominantly female, have a bimodal age distribution, and a predilection for disease on the oral tongue. Other retrospective studies have explored this NSND group, and whilst they concur that the group is more likely to be female and have oral cavity tumours, no consensus pattern in age distribution or survival outcomes has emerged [8,9,10,11,12,13,14,15]. One previous study reported poorer survival in the NSND group, but this was confined to young NSND patients [12], whilst another found a non-significant trend towards improved survival in the NSND group as a whole [11]

Methods

Results

Conclusion