PD-L1 Testing and Squamous Cell Carcinoma of the Head and Neck: A Multicenter Study on the Diagnostic Reproducibility of Different Protocols

SIMPLE SUMMARY: The introduction of therapies with immune checkpoint inhibitors targeting the programmed cell death protein 1 and its ligand (PD-L1) axis in head and neck squamous cell carcinoma prompted the need of reliable bio-selectors to stratify patients that would benefit from these treatments. The assessment of PD-L1 expression through immunohistochemistry represents the most widely used method to perform this task, being recently approved by regulatory authorities. However, borrowing from previous experiences in lung cancer, the heterogeneity of antibodies and platforms used in the routine clinical practice requires a strict multi-institutional harmonization effort. In this setting, the present study is aimed to assess the performances of different PD-L1 staining protocols and the inter-observer reliability for its interpretation. ABSTRACT: Immune checkpoint inhibitors for blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are now available for squamous cell carcinoma of the head and neck (HNSCC) in relapsing and/or metastatic settings. In this work, we compared the resulting combined positive score (CPS) of PD-L1 using alternative methods adopted in routine clinical practice and determined the level of diagnostic agreement and inter-observer reliability in this setting. The study applied 5 different protocols on 40 tissue microarrays from HNSCC. The error rate of the individual protocols ranged from a minimum of 7% to a maximum of 21%, the sensitivity from 79% to 96%, and the specificity from 50% to 100%. In the intermediate group (1 ≤ CPS < 20), the majority of errors consisted of an underestimation of PD-L1 expression. In strong expressors, 5 out of 14 samples (36%) were correctly evaluated by all the protocols, but no protocol was able to correctly identify all the “strong expressors”. The overall inter-observer agreement in PD-L1 CPS reached 87%. The inter-observer reliability was moderate, with an ICC of 0.774 (95% CI (0.651; 0.871)). In conclusion, our study showed moderate interobserver reliability among different protocols. In order to improve the performances, adequate specific training to evaluate PD-L1 by CPS in the HNSCC setting should be coordinated.