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

Ping-Li Sun · 2021-09-03

Aims

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 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 = 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.