Prognostic Value of an Integrated Human Papillomavirus and Immunoscore Model to Predict Survival in Vulva Squamous Cell Carcinoma
Although the prognostic value of immune-related biomarkers is well characterized in many solid tumors, their significance in vulva squamous cell carcinoma (VSCC) remains unclear. In this study, we report a comprehensive analysis of programmed death ligand protein 1 (PD-L1) and immune cell infiltration in VSCC and establish immunoscore models for classification of the disease. Tissue microarrays, immunohistochemistry, and digital quantification were used to investigate the number of CD4+, CD8+, CD68+, CD14+, FoxP3+, and PD-L1+ cells in epithelial and stromal compartments of VSCC (n = 117). Immunoscores were developed using these parameters and applying the least absolute shrinkage and selection operator to identify predictors of survival. Immunoscores were then integrated with human papillomavirus (HPV) status, as determined using messenger RNA in situ hybridization, to construct internally validated nomograms. The prognostic models were subsequently applied in whole tissue sections (n = 25) to investigate agreement. Advanced VSCC (International Federation of Gynecology and Obstetrics stage III/IV) was characterized by high densities of CD68+ macrophages and PD-L1+ cells (Spearman correlation, ρ = 0.80) in the epithelium. PD-L1 status independently predicted poor progression-free survival (PFS) (hazard ratio = 1.828; 95% CI, 1.039-3.215; P = .036). Immunoscore