PD-L1 Expression in head and neck squamous cell carcinoma: qualitative or quantitative assessment? Is that enough or we need something more?

The Combined Positive Score (CPS) currently represents the sole biomarker employed in clinical practice to predict the efficacy of immune checkpoint inhibitors (ICIs) and to guide optimal personalized treatment sequencing in head and neck squamous cell carcinoma (HNSCC). However, CPS alone is insufficient for accurate patient stratification and prediction of ICI response, necessitating integration with additional immune-related biomarkers. The spatial distribution of programmed death ligand-1 (PD-L1) expressing cells may offer a promising approach to more comprehensively characterize both the tumor microenvironment (TME) and malignant cells, elucidate their interactions, and enhance the predictive value regarding response to ICI therapy.This perspective aims to investigate the potential role of spatial assessment of PD-L1 expression in improving patient stratification and therapeutic outcomes in HNSCC.