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BACKGROUND: Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. Limited treatment options highlight the need for precision therapeutics. PATIENTS AND METHODS: We investigated the correlation between diverse clinical features and genetic changes using next-generation sequencing data derived from our recent umbrella trial. We analyzed the targeted DNA and RNA sequencing data profiles of 419 patients with HNSCC enrolled in the recent genomic-based umbrella trial. Comprehensive analyses, including survival analysis, were conducted to assess the overall genetic landscape, mutational signature patterns, copy number variations, and their correlation with patient outcomes. RESULTS: Multiple genomic aberrations served as predictive factors in patients treated with targeted therapies. NOTCH1 mutations and MYC amplification were associated with worse prognosis (P = 0.0037 and P = 0.0016, respectively). CDKN2A mutations influenced the clinical outcome of patients treated with CDK4/6 inhibitors, with divergent effects based on mutation types (improved survival with deletions and poor survival with SNV/indels). p16 positivity was correlated with a favorable prognosis in patients who underwent immunotherapy during the TRIUMPH trial. Stratification of such groups revealed novel genomic characteristics, such as mutual exclusiveness between TP53 and PIK3CA SNV/indels in HPV-positive oropharyngeal cancer, along with a high prevalence of TP53 mutations in young patients with oral-cavity cancer, which were unrelated to germline predisposing mutations, smoking habits, or p16 expression. CONCLUSION: Genomic profiling plays a significant role in the management of recurrent or metastatic HNSCC and may help identify potential targets for precision therapeutics.
Hwang et al. (Wed,) studied this question.