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

Deuss, Eric and Kuerten, Cornelius and Fehr, Lara and Kahl, Laura and Zimmer, Stefanie and Künzel, Julian and Stauber, Roland H. and Lang, Stephan and Hussain, Timon and Brandau, Sven (2024) Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications. CANCERS, 16 (11): 2103. ISSN 2072-6694

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Abstract

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was >= 20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS >= 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1.

Item Type: Article
Uncontrolled Keywords: TUMOR-INFILTRATING LYMPHOCYTES; CLINICOPATHOLOGICAL SIGNIFICANCE; NIVOLUMAB; RECURRENT; IMMUNOTHERAPY; CHEMOTHERAPY; IPILIMUMAB; METASTASES; programmed cell death 1 Ligand 1 (PD-L1); combined positivity score (CPS); tumor proportion score (TPS); heterogeneity; head and neck squamous cell carcinoma (HNSCC); biomarker; prognosis; oropharyngeal squamous cell carcinoma (OPSCC); p16; HPV
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Jan 2026 07:09
Last Modified: 22 Jan 2026 07:09
URI: https://pred.uni-regensburg.de/id/eprint/65167

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