Intratumoral heterogeneity of PD-L1 expression in head and neck squamous cell cancers and its clinical relevance

Background In head and neck squamous cell carcinoma (HNSCC), the indication for PD-1 antibody therapy is based in part on the combined positive score (CPS) of PD-L1 expression. The absolute CPS is not decisive for the therapy decision, but the classification into the categories: CPS < 1, CPS 1 – 20, or CPS > 20. In this study, we investigated the heterogeneity of PD-L1 expression (CPS) within primary tumors (PT) as well as between PT and lymph node metastases (LNM) along with local recurrences (LR) in patients with HNSCC and its influence on clinical therapy decisions.

Material and Methods CPS was determined by immunohistochemistry on two intratumoral tissue samples each from 111 HNSCC PT. Additional samples from LNM were analyzed in 33.3% of PTs, and additional samples of associated LR were available in 10% of cases. Expression analysis was performed using QuPath v0.2.3.

Results There were no significant intratumoral differences when comparing the absolute CPS of PT, LNM, or LR. However, when classified into the three therapy-relevant CPS categories, a high number of cases showed differences that could have led to a change in PD-1 antibody-based therapy regimen; both when comparing intratumoral samples (36%), and when comparing CPS between PT and LNM (49%) as well as among PT and LR (64%). A CPS value over 20 was also associated with higher 5-year overall survival (hazard ratio: 0,48; p = 0.04; confidence interval: 0,24 – 0,97).

Conclusion HNSCC reveal intratumoral heterogeneity in PD-L1 expression, which has therapy-relevant impact for classification into CPS categories. Therfore, obtaining and analyzing multiple tissue samples may be useful for optimizing individual therapy regimens.

Publication History

Article published online:
12 May 2023