Vulvar cancer: Two pathways with different localization and prognosis

Abstract

Background: Two etiologic pathways for vulvar squamous cell carcinoma (SCC) are described: in a background of lichen sclerosus and/or differentiated vulvar intraepithelial neoplasia and related to high-risk human papillomavirus (HPV) infection with high grade squamous intraepithelial lesion (HSIL) as precursor. The aim was to compare the predilection site and survival of HPV-related to non HPV-related vulvar SCCs.

Methods: Data of patients treated for primary vulvar SCC at the Radboudumc between March 1988 and January 2015 were analyzed. All histological specimens were tested for HPV with the SPF₁₀/DEIA/LiPA₂₅ system assay and p16^INK4a staining was performed using CINtec® histology kit. Vulvar SCCs were considered HPV-related in case of either >25% p16^INK4a expression and HPV positivity or >25% p16^INK4a expression and HSIL next to the tumor without HPV positivity. Tumor localization, disease specific survival (DSS), disease free survival (DFS) and overall survival (OS) of patients with HPV-related and non HPV-related vulvar SCC were compared.

Results: In total 318 patients were included: 55 (17%) had HPV-related (Group 1) and 263 (83%) had non HPV-related vulvar SCC (Group 2). Tumors in Group 1 were significantly more often located at the perineum compared to Group 2, 30% and 14%, respectively (p=0.001). The DSS, DFS and OS were significantly better in HPV-related than in non HPV-related vulvar SCC patients.

Conclusion: HPV-related vulvar SCCs are more frequently located at the perineum and have a favorable prognosis compared to non HPV-related vulvar SCCs. Both localization and HPV-relation could explain this favorable prognosis. HPV-related vulvar SCC seems to be a separate entity.

Keywords: Disease specific survival; Etiology; HPV; Human papillomavirus; Prognosis; Tumor localization; Vulvar cancer; p16(INK4a) expression.