Exploring novel therapeutic targets in vulvar squamous cell carcinoma.

OBJECTIVE

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with limited treatment options for advanced disease. This study investigates potential antibody drug conjugate (ADC) targets and explores the immune microenvironment in VSCC.

METHODS

Immunohistochemistry (IHC) was performed on tissue microarrays (TMAs) with cores from patients with VSCC to evaluate 6 potential ADC targets: Human Epidermal Growth Factor Receptor 2 (HER2), Trophoblast Cell Surface Antigen 2 (TROP2), Tissue Factor (TF), NECTIN4, Folate Receptor Alpha (FOLR1) and Claudin-18.2 (CLDN18.2). Expression of TROP2, TF and NECTIN4 was quantified using H-score. Multiplex IHC assessed immune markers (CD3+, CD8+, CD68+, PD-1/PD-L1) and combined positive scores (CPS) for programmed death-ligand 1 (PD-L1) were calculated. Clinical data was collected, including p16 and p53 status.

RESULTS

CLDN18.2 and FOLR1 were negative in all cases (n = 108) and HER2 expression was seen in only 2 cases. Intermediate to high H-score (100-300) was observed for TF in 73 % (n = 78), TROP2 in 74 % (n = 80), and NECTIN4 in 53 % (n = 57). All cases had a PD-L1 CPS ≥1 and median CPS was 66 (IQR 28-100) Exploratory analysis suggests ADC marker expression was not dependent on human papillomavirus (HPV) status. However, HPV-independent tumors appeared to have a higher infiltration of CD8+ and CD68+ cells and higher median CPS compared to HPV-associated tumors.

CONCLUSIONS

These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.