Abstract
Management options are limited in advanced or recurrent cervical carcinoma. The Food and Drug Administration has recently approved programed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) inhibitors for the treatment of advanced PD-L1 positive cervical cancer. We studied PD-L1 expression in cervical squamous cell carcinoma (CSCC) samples initially on a The tissue microarray and then in full-tissue sections from poorly differentiated (grade 3) cancers. Tissue microarray was composed of 45 grade 3 and 2 (moderately differentiated) tumors. PD-L1 expression was evaluated as categorical data and by obtaining combined positive score of neoplastic and mononuclear inflammatory cells. In tissue microarray samples PD-L1 expression was higher in poorly differentiated cancers compared with grade 2 tumors by immunohistochemistry. Full-tissue sections from grade 3 CSCC (n=22) were stained with PD-L1, CD8, and VEGF antibodies. Poorly differentiated CSCC samples had diffuse (≥50%) and focal/patchy staining patterns. The latter pattern showed localized tumor-stroma interface staining in 5 samples with low combined positive score. Importantly, younger patients (median=36) had tumors with higher expression. PD-L1 expression was associated with larger tumor size and absent lymphovascular invasion. In addition, CD8 tumor-infiltrating lymphocyte density within the neoplastic tissue matched with PD-L1 levels. The overall survival rates did not correlate with PD-L1 expression. However, in early-stage disease high CD8 tumor-infiltrating lymphocyte density within the peritumoral stroma was associated with better survival outcomes in multivariate analysis. PD-L1 expression and CD8 tumor-infiltrating lymphocyte density may be useful to define a subgroup of patients with relatively better prognosis in poorly differentiated CSCC. It is warranted to validate our results in a larger sample size.