Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+Oropharyngeal Squamous Cell Carcinoma

center dot Context.-Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS). Objective.-To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC). Design.-We identified 38 resected p16+ OPSCCs for which paired PTs and LMs were available. PD-L1 immu-nohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement. Results.-Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens (j = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (j= 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution (j = 0.84). Conclusions.-Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of p16+ OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy. (Arch Pathol Lab Med. 2023;147:442-450; doi: 10.5858/ arpa.2021-0464-OA)

Automated summary

This study compared the programmed death ligand-1 (PD-L1) expression scores derived from resected primary tumors and lymph node metastases in patients with head and neck squamous cell carcinoma. The results showed high interobserver and interspecimen variability in the scoring, suggesting the need for additional material or observers when evaluating PD-L1 expression in p16+ oropharyngeal squamous cell carcinoma.