Poliovirus receptor ( CD155 ) expression in gastric‐type adenocarcinoma of the cervix compared with human papillomavirus–associated and other human papillomavirus–independent adenocarcinomas

AIMS: Gastric-type adenocarcinoma (GAS), a human papillomavirus-independent (HPVI) histological type of cervical adenocarcinoma, has a poorer prognosis and a distinct immune microenvironment compared with HPV-associated (HPVA) adenocarcinoma. Poliovirus receptor (PVR, CD155) is an immune-checkpoint ligand that suppresses antitumour immunity, but its expression in GAS is unknown. We aimed to characterize PVR expression across histological groups of cervical adenocarcinoma and its clinicopathological and immunological correlates. METHODS AND RESULTS: We retrospectively studied 142 patients with cervical adenocarcinoma (37 GAS, 92 HPVA and 13 HPVI [non-GAS] cases). PVR, PD-L1 (combined positive score [CPS] and tumour area positivity [TAP]) and CD8-positive tumour-infiltrating lymphocytes were quantified immunohistochemically. PVR positivity (H-score ≥ 50) was present in all GAS cases (100%), versus 56.5% of HPVA and 69.2% of HPVI (non-GAS) cases and the PVR H-score differed significantly among groups, with the highest median in GAS (112.8 vs. 70.8 in HPVA and 98.2 in HPVI [non-GAS]; P < 0.001). PVR expression correlated significantly with CPS and TAP but not with CD8 density, and was associated with advanced stage. High PVR expression (H-score >100) was associated with poorer overall and recurrence-free survival in univariable analysis (both P < 0.001), but this association was not maintained after adjustment for stage and histological group. CONCLUSIONS: PVR expression was highest in GAS among the histological groups and correlated with PD-L1 scores (CPS and TAP) and aggressive clinicopathological features, but was not an independent prognostic marker after adjustment for stage and histology. These findings support further investigation of PVR as a therapeutic target in GAS.