Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation

•SCCHN tumor sequencing is useful for outcome prediction of adjuvant chemoradiation•Unfavourable subgroup of tobacco-related SCCHN displays hotspot TP53 mutations•PIK3CA, KRAS and NRAS mutations in HPV+ SCCHN are associated with reduced survival.•Mutant p53 and the phosphoinositide 3-kinase pathway represent druggable targets.