Programmed death‐ligand 1 expression in human papillomavirus‐independent cervical adenocarcinoma and its prognostic significance

In the 2020 World Health Organization classification of female genital tumours, endocervical adenocarcinomas (ECAs) are subclassified into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) groups on the basis of their distinct aetiologies and clinical behaviours. The aim of this study was to investigate programmed death-ligand 1 (PD-L1) expression and its prognostic value in HPVI ECA and HPVA ECA, and compare these between the two entities.A total of 93 ECAs accessioned between 2013 and 2020 were selected for further analysis, including 48 usual-type HPVA ECAs and 45 HPVI ECAs. Then, we evaluated PD-L1 expression in whole tissue sections of these cases by using the tumour proportion score (TPS) and the combined positive score (CPS). Heterogeneous PD-L1 expression was observed in both HPVI ECAs and usual-type HPVA ECAs. However, no significant difference in PD-L1 expression was seen among different histological types of ECA when either the CPS or the TPS was used. Gastric-type ECA (GEA) was associated with higher clinical stage (P = 0.001), worse progression-free survival (PFS) (P = 0.008) and worse overall survival (OS) (P = 0.02) than usual-type HPVA ECA and non-GEA HPVI ECA. When the TPS was used, PD-L1-positive GEA was associated with significantly worse PFS (P = 0.03) and OS (P = 0.015) than PD-L1-negative GEA.Our data show frequent PD-L1 expression in HPVI ECAs, supporting the potential role of the programmed cell death protein 1/PD-L1 pathway as a therapeutic target for these tumours. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavourable outcome for GEAs.