PD‐L1 expression and immune stromal features in HPV‐independent cervical adenocarcinoma

Abstract

Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. Methods: We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%.Results: PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumourinfiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P = 0.004 and P = 0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. Conclusions: Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

Is there different prognosis between cervical endometrioid adenocarcinoma and ordinary cervical adenocarcinoma in a propensity score matching study based on the surveillance, epidemiology, and end results (SEER) database?

“…Some research has suggested that the prognosis of each AC varies according to its histopathological type ( 12 , 22 , 28 - 30 ). Some investigators have suggested that different subtypes of cervical AC may be different at the molecular level ( 31 , 32 ), Taken as a whole, from a clinical point of view, our results suggest that EC may be associated with better survival than AC even after PSM. However, these results need to be confirmed in prospective studies with large-sample sizes.…”

HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications

“…Studies about PDL1 expression in NHPVA are limited. Recently, Song and Chen investigated PDL1 expression among different histotypes of NHPVA and its correlation with prognosis, progression-free survival, and overall survival [ 107 , 108 ].…”

“…CPS is defined as the number of PDL1 stained cells (tumor cells, lymphocytes, and macrophages) divided by the total number of viable tumor cells and then multiplied by 100. TPS is the percentage of viable tumor cells showing partial or complete membrane staining adenocarcinoma positive or PDL1 expression [ 107 , 108 ].…”

“…This study showed a higher association between PDL1 positivity and CCC when TPS defined PDL1 positivity (58.3% PDL1 positivity vs. 14.3% positivity for gastric type adenocarcinoma and 40% positivity for endometrioid adenocarcinoma). PDL1 was not expressed in mesonephric carcinoma cases [ 107 ].…”

“…PDL1 expression was significantly associated with a high tumor-infiltrating lymphocyte percentage and with worse progressive free survival and overall survival rate [ 107 ].…”