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

Histopathology. 2022 Jan;80(2):338-347. doi: 10.1111/his.14552. Epub 2021 Oct 13.

Abstract

Aims: 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.

Methods and results: 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.

Conclusions: 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.

Keywords: HPV-independent; PD-L1; cervical cancer; endocervical adenocarcinoma; survival.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor
  • Cervix Uteri / metabolism*
  • Cervix Uteri / pathology
  • Female
  • Humans
  • Papillomavirus Infections / pathology
  • Prognosis
  • Survival Rate
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor