Considerable interlaboratory variation in PD‐L1 positivity for head and neck squamous cell carcinoma in the Netherlands— A nationwide evaluation study

Aims Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are eligible for first‐line immune checkpoint inhibition if their tumour is positive for programmed death ligand 1 (PD‐L1) determined by the combined positive score (CPS). This nationwide study, using real‐world data, investigated the developing PD‐L1 testing landscape in the first 3 years after introduction of the test in HNSCC and examined interlaboratory variation in PD‐L1 positivity rates. Methods Pathology reports of HNSCC patients mentioning PD‐L1 were extracted from the Dutch Pathology Registry (Palga). Tumour and PD‐L1 testing characteristics were analysed per year and interlaboratory variation in PD‐L1 positivity rates was assessed using funnel plots with 95% confidence limits around the overall mean. Results A total of 817 PD‐L1 tests were reported in 702 patients among 19 laboratories; 85.2% of the tests on histological material were stated to be positive. The national PD‐L1 positivity rate differed significantly per year during the study period (79.7–89.9%). The use of the recommended 22C3 antibody increased from 59.9 to 74.3%. A total of 673 PD‐L1 tests on histological material from 12 laboratories were analysed to investigate interlaboratory variation. Four (33%) deviated significantly from the national mean of PD‐L1‐positive cases using CPS ≥ 1 cut‐off, while two (17%) deviated significantly for CPS ≥ 20 cut‐off. Conclusion In the first 3 years of PD‐L1 assessment in HNSCC, the testing landscape became more uniform. However, interlaboratory variation in PD‐L1 positivity rates between Dutch laboratories was substantial. This implies that there is a need for further test standardisation to reduce this variation. The first 3 years of PD‐L1 testing in head and neck squamous cell carcinoma were evaluated in this nationwide real‐world data study. Although PD‐L1 assessment methods became more uniform, interlaboratory variation in PD‐L1 positivity rates remained substantial.