Assessing PD-L1 Expression in Head and Neck Squamous Cell Carcinoma: Trials and Tribulations

Immune checkpoint inhibitors have improved the outcome of patients diagnosed with inoperable recurrent or metastatic head and neck squamous cell carcinoma. However, as only a subset of head and neck cancer patients benefit from this treatment, biomarkers predicting treatment response help guide physicians in their clinical decision-making. PD-L1 expression assessed by immunohistochemistry is the single most clinically relevant biomarker predicting response to PD-1-blocking antibodies. Here, we discuss in which clinical context assessment of PD-L1 expression is instrumental for the choice of therapy, how pathologists score it, and how it affects the approval of anti-PD-1 antibodies. Furthermore, we discuss the heterogeneity of PD-L1 expression and review technical aspects of determining this prominent biomarker-knowledge that might influence clinical decision-making.