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

Abstract

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 immunohistochemistry 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 (κ = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (κ = 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 (κ = 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.

Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists

“…Data on CPS interpretation at clinically significant thresholds has been mixed. 11,12,13 Although no prior studies have specifically focused on PD-L1 CPS interobserver agreement in cervical carcinoma among gynecologic pathologists, results from 32 pathologists who underwent 2 days of digital and expert-to-peer training showed good agreement (kappa 0.771) at the CPS ≥ 1 threshold in cervical carcinoma, with similar to the slightly higher agreement seen for cohorts of gastric, esophageal, urothelial, and head and neck carcinomas. 14 However, such intensive standardized training in PD-L1 interpretation is not common in clinical settings, and PD-L1 CPS agreement among expert pathologists in routine gynecologic practice using glass slides has not been well studied.…”

“…It has since become the dominant methodology for scoring PD-L1 immunohistochemistry (IHC) in most organ systems and tumor types, with additional FDA-approved indications in cervical carcinoma, breast carcinoma, urothelial carcinoma, and head and neck carcinoma. Data on CPS interpretation at clinically significant thresholds has been mixed 11,12,13 . Although no prior studies have specifically focused on PD-L1 CPS interobserver agreement in cervical carcinoma among gynecologic pathologists, results from 32 pathologists who underwent 2 days of digital and expert-to-peer training showed good agreement (kappa 0.771) at the CPS ≥1 threshold in cervical carcinoma, with similar to the slightly higher agreement seen for cohorts of gastric, esophageal, urothelial, and head and neck carcinomas 14 .…”

Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications

“…Previous studies also show these potentially treatment-relevant differences in 15% to 44% of cases. Although not significant, in some cases pairwise comparisons between primary tumor and lymph node showed a substantially lower PD-L1 expression in the lymph node [ 28 , 32 , 36 , 37 , 38 , 39 ]. This may explain some of the differences in response between the primary tumor and lymph node observed in neoadjuvant immunotherapy seen in clinical trials [ 11 , 31 , 38 , 39 , 40 ].…”