PD-L1 expression in HPV-independent cervical adenocarcinoma and its prognostic significance.

Abstract

AIM\nIn 2020 WHO Classification of Female Genital Tumors, endocervical adenocarcinomas (ECAs) are subclassified into HPV-associated (HPVA) and HPV-independent (HPVI) groups based on their distinct etiology and clinical behavior. This study aimed to investigate Programmed death-1 ligand (PD-L1) expression and its prognostic value in HPV-independent (HPVI) endocervical adenocarcinoma (ECA) and compare it with HPV-associated (HPVA) ECA.\n\n\nDESIGN AND RESULTS\nA total of 93 cases of ECA accessioned between 2013 and 2020 were selected for further analysis, including 48 cases of usual type HPVA and 45 cases of HPVI ECA. Then, we evaluated PD-L1 expression in whole tissue sections of these cases by using tumor proportion score (TPS) and combined positive score (CPS) scoring methods. Heterogenous expression of PD-L1 was observed in both HPVI and usual type HPVA ECA cases. However, no significant difference in PD-L1 expression was seen among different histologic types of ECAs using either CPS or TPS. Gastric type ECA (GEA) is associated with higher clinical stage (p=0.001), worse progression free survival (PFS) (p=0.008) and overall survival (OS) (p=0.02) compared to usual type HPVA ECAs and non-GEA HPVI ECAs. Using TPS, PD-L1-positive GEAs demonstrated significantly worse PFS (p=0.03) and OS (p=0.015) when compared to PD-L1 negative GEAs.\n\n\nCONCLUSIONS\nOur data show frequent PD-L1 expression in HPVI ECAs, supporting the potential role of the PD-1/PD-L1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome for GEAs.