Abstract

Oral squamous cell carcinoma (OSCC) is a major issue in the sphere of head and neck cancer since it is very heterogeneous, which also leads to the poor treatment results and low survival rates in the advanced stages. Here, the review will discuss how spatial omics methods explore tumor heterogeneity in OSCC, which includes cellular, molecular, and immune microenvironment alterations that occur due to cancer stem cells, stromal interactions, genetic instability, epigenetic reorganization, and metabolic reprogramming. The focus of heterogeneity is given on the contribution of the tumor microenvironment such as immune cells, cancer-associated fibroblasts and extracellular matrix remodeling to the stimulation of progression, metastasis, as well as therapeutic resistance. The introduction of spatial omics technologies, including spatial transcriptomics, proteomics, and metabolomics, has revolutionized the field by preserving tissue architecture, enabling high-resolution mapping of gene expression, protein distribution, and metabolite profiles. Significant developments around the spatial omics technologies are discussed, while how they are used in the identification of ligand-receptor network, signaling pathways, and spatial patterns of heterogeneity in OSCC are described. Integration of multi-omics approaches bridges gaps between transcriptomic, proteomic and metabolic, facilitating the discovery of biomarkers for prognosis, immune evasion mechanisms, and precision therapies targeting epithelial-to-mesenchymal transition and immunosuppressive networks. Despite challenges in data integration, cost, and clinical translation, spatial omics holds promise for personalized oncology, with future directions involving artificial intelligence-driven modeling to enhance diagnostic accuracy and therapeutic efficacy in OSCC management.