Mutational profile of HPV-driven head and neck cancers according to tobacco consumption.

Abstract

e17535 Background: HPV-driven oropharyngeal cancer (OPC) patients are characterized by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and studies have highlighted that among HPV-positive patients those with a smoking history have a significantly increased risk of disease progression and death compared to those who have never smoked. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study is to characterize the mutational profile of HPV-positive OPC by smoking status. We hypothesize a higher frequency of mutations affecting among smokers. Methods: Targeted next-generation sequencing of 38 oncogenes/tumor suppressor genes that are commonly mutated in cancers caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases stratified by smoking status. Results: The study population included 37 (60%) non-smokers and 25 (40%) smokers distributed as follows: 1 (4%) patient smoked <10 pack-year (PY), 8 (32%) patients between 10-20 PY and 16 (64%) >20 PY. Twenty (31%) patients had no mutation, 14 (23%) had 1 mutation and 28 (46%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (20%), MLL2 (20%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH 1 (9%) and FGFR3 (9%). Mutation rate was not significantly different in smokers compared to non-smokers even when analyses focused on heavy smokers (>20 pack-years compared to <20 pack-years). Similarly there was no significant difference in mutations patterns according to tobacco consumption. The 3 years overall survival, disease-specific-survival and loco-regional-control rates for the whole cohort are respectively 88% (95% CI: 76.4-94.1), 88% (95% CI: 76.4-94.1) and 80.6% (95% CI: 67.5-88.8). Despite a median follow-up was 4.5 years (6 months to 11.7 years), the few number of events (13 relapses, 13 deaths including 10 due to OPC) precludes detailed prognosis analyses. Conclusions: HPV-driven OPC patients with a smoking history have a comparable mutational rate than non-smokers. Smoking impact on the prognosis isn’t attributable to the mutational burden. Further studies are warranted.