Background: The role of immune checkpoint inhibition (ICI) in treating head and neck squamous cell carcinoma (HNSCC) is expanding, yet response rates to PD-L1 therapy remain inconsistent. The variability in PD-L1 therapy response between primary tumors and associated lymph node metastases remains unclear.

Methods: Primary tumors and matching lymph node metastases from 50 patients were analyzed using PD-L1 immunohistochemistry. PD-L1 expression was evaluated using the combined positive score (CPS) and the tumor proportion score (TPS), while immune infiltration was assessed with an immunoreactive score (IRS). These measures were compared between primary tumors and lymph node metastases and correlated with other clinical features.

Results: PD-L1 expression, evaluated by CPS and TPS, showed no significant differences between the primary tumor and matched lymph node metastases. However, 18% (CPS) respectively 4% (TPS) of patients showed clinically relevant discordance between primary tumors and lymph node metastases based on FDA and EMA approval cutoffs. CPS and TPS were not affected by tumor subsite or HPV status, while IRS was significantly influenced by primary tumor location. Both HPV status and tumor subsite were significantly associated with overall survival.

Conclusion: This study highlights the heterogeneity of PD-L1 expression in HNSCC and suggests potential explanations for the varied response to ICI. Consequently, an in-depth exploration of PD-L1 expression in HNSCC, coupled with innovative strategies to enhance patient eligibility for ICI, is essential for improving prognostication and establishing a rationale for re-biopsies, particularly in the context of lymph node metastases, when initial therapeutic thresholds for anti-PD-1 therapy are not achieved.

Nein.