Current Evidence of Precision Medicine via Multi‐Omic Approaches in Head and Neck Squamous Cell Carcinoma

BACKGROUND: Perioperative and adjuvant immunotherapy are new standards of care for selected patients with resectable locoregionally advanced HPV-negative HNSCC, but low pathologic response rates and a lack of predictive biomarkers limit patient selection and response-adapted care. This review examines multi-omic approaches to predicting immunotherapy response and personalizing therapy. METHODS: A narrative review of current multi-omic strategies for HNSCC was performed. Data providing predictive, prognostic, diagnostic, surveillance, or exploratory value was summarized. RESULTS: Multi-omics may identify those likely to benefit from immunotherapy. Single-cell transcriptomics reveals changes in the tumor immune microenvironment while spatial proteomics reveals tertiary lymphoid structures, dendritic cell networks, and protein signatures predicting immunotherapy response. Obstacles include unstandardized protocols, limited prospective validation, and small sample sizes. CONCLUSIONS: Multi-omics can reshape biomarker-driven HNSCC care, but implementation requires prospective validation, standardized protocols, and multi-platform integration.