Challenges facing pathologists evaluating PD‐L1 in head & neck squamous cell carcinoma

Abstract

Background Programmed death‐ligand 1 (PD‐L1) expression with combined positive score (CPS) ≥1 is required for administration of checkpoint inhibitor therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The 22C3 pharmDx Dako immunohistochemical assay is the one approved as companion diagnostic for pembrolizumab, but many laboratories work on other platforms and/or with other clones, and studies exploring the potential interchangeability of assays have appeared. Evidence from the literature After review of the literature, it emerges that the concordance among assays ranges from fair to moderate, with a tendence of assay SP263 to yield a higher quota of positivity and of assay SP142 to stain better immune cells. Moreover, pathologists achieve very good concordance in assessing PD‐L1 CPS, particularly with SP263. Conclusions Differences in terms of platforms, procedures, and study design still preclude a quantitative synthesis of evidence and clearly further work is needed to draw stronger conclusions on the interchangeability of PD‐L1 assays in HNSCC.

Concordance between Three PD-L1 Immunohistochemical Assays in Head and Neck Squamous Cell Carcinoma (HNSCC) in a Multicenter Study

“…In both studies, pathologists had received dedicated training in the assessment of CPS in HNSCC [ 15 ]. These results are strong evidence that training programs to update pathologists on new criteria to be applied for in situ biomarker evaluation are highly effective [ 9 , 14 ].…”

“…An accessible, reproducible, and robust IHC test for the evaluation of PD-L1 expression in terms of CPS is therefore crucial to guide therapy decisions in patients with HNSCC. However, technical and biological issues still hamper CPS assessment by pathologists in the clinical practice [ 9 , 10 ]. First, several antibody clones and platforms have been developed for the immunohistochemical analysis of PD-L1 expression.…”

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers

“…Currently, PD-L1 expression is mainly detected using immunohistochemical methods, and there is considerable variability with respect to the positive thresholds set by different studies, the antibody detection platforms and the detection techniques used. Recent studies have analyzed assays for evaluating PD-L1 expression, and the results demonstrated that SP263 assay tended to increase the degree of positive expression while SP142 assay tended to stain better immune cells ( 50 ). Cerbelli explored the inter-observer reliability and correlation between PD-L1 expression assays, which revealed high agreement between the 22C3 PharmDx assay and the SP263 assay, suggesting that the two antibodies are interchangeability in immunotherapy ( 51 ).…”

A digital assay for programmed death-ligand 1 (22C3) quantification combined with immune cell recognition algorithms in non-small cell lung cancer

“…With complexities related to IVD staining performances, various scoring methods (TPS/ tumor cell population versus immune cells/total tumor area versus combined positive scoring [CPS]), and intratumor heterogeneity, many studies have shown substantial differences between pathologists’ interpretation of PD-L1 staining and resulting TPS 2 , 5 , 6 . This is not only a challenge related to NSCLC, but a difficulty amongst a multitude of cancer therapies 4 , 12 . Future refinement may lead to further improvement in prediction algorithms (based on TPS score in NSCLC and CPS in others cancer therapies 12 ) for response to checkpoint inhibitor therapy.…”