Immunohistochemical and serum profile of squamous cell carcinoma of the vulva: The Dual Vulvar Panel (DVP) project

Introduction: This study aimed to evaluate the expression of selected immunohistochemical (IHC) markers and serum squamous cell carcinoma antigen (SCC-Ag) in vulvar squamous cell carcinoma (VSCC), and to investigate associations with recurrence and death using molecular clustering and diagnostic performance analyses. Study design: This single-centre prospective study included 27 patients with histologically confirmed VSCC. Tumour specimens were assessed for expression of p16, p53, programmed death-ligand 1 (PD-L1), CD44 and epidermal growth factor receptor (EGFR). Serum SCC-Ag was measured and correlated with clinical outcomes. Statistical analyses comprised Pearson’s correlation, logistic regression, receiver operating characteristic curve analysis, diagnostic performance metrics, and unsupervised hierarchical clustering integrating IHC and SCC-Ag data. Results: No significant associations were observed between individual IHC markers and clinical outcomes. Serum SCC-Ag showed a positive trend towards association with recurrence (r = 0.462; p = 0.071), with an increased odds ratio (OR) (OR = 2.7). When analysed as a binary variable, SCC-Ag demonstrated sensitivity of 50%, specificity of 76%, and overall accuracy of 70%. As a continuous variable, SCC-Ag achieved an area under the curve value of 0.83. The combination of SCC-Ag and p53 improved sensitivity to 83% and negative predictive value to 89%. Unsupervised hierarchical clustering identified three biological subgroups, with the cluster characterized by high SCC-Ag and EGFR expression and low p16 expression associated with recurrence more frequently. Conclusion: Serum SCC-Ag showed superior prognostic performance compared with individual IHC markers, and may be useful for postoperative risk stratification in VSCC. Combined biomarker panels, including p53, PD-L1, EGFR and p16, yielded promising sensitivity, supporting future strategies.