Identifying predictive markers of head and neck squamous cell carcinoma in an umbrella trial (KCSG HN 15-16 TRIUMPH...

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.

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.

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.

Genomic profiling plays a significant role in the management of recurrent or metastatic HNSCC and may help identify potential targets for precision therapeutics.