Radiomics as a spatial context for treatment decision-making in head and neck cancer.

Radiomics has been widely explored as a non-invasive biomarker in head and neck squamous cell carcinoma (HNSCC), yet its clinical role remains unclear. Tissue-based biomarkers differ in their susceptibility to spatial sampling. Biomarkers such as PD-L1 expression, immune-cell infiltration, necrosis, and immune exclusion may exhibit substantial spatial heterogeneity, whereas HPV/p16 status and some genomic alterations are generally more stable across the tumor. Nevertheless, localized sampling may incompletely capture heterogeneity in selected clinical contexts. This mismatch becomes clinically relevant when treatment decisions, particularly for chemoradiotherapy, immunotherapy, or de-escalation, are based on potentially non-representative biopsy findings. In this narrative review, we argue that the role of radiomics is not to outperform established biomarkers, but to contextualize them by capturing spatial heterogeneity related to hypoxia, necrosis, stromal architecture, and immune exclusion. We synthesize current evidence linking radiomic features to these biological processes and map them to specific clinical decision points, including larynx preservation, immunotherapy stratification, and recurrence assessment. Rather than serving as a standalone predictor, radiomics may provide complementary spatial information that helps identify situations in which biopsy-derived biomarkers should be interpreted with caution. Although current evidence is largely retrospective, radiomics offers a pragmatic framework for integrating spatial information into biomarker-guided clinical workflows.