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

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.

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%.

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 tumour-infiltrating 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.

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.