There are two etiologic pathways for vulvar squamous cell carcinoma (SCC). The first occurs in a background of lichen sclerosus and/or differentiated vulvar intraepithelial neoplasia (dVIN). The second is related to high-risk human papillomavirus (HPV) infection with its precursor lesion high grade squamous intraepithelial lesion (HSIL). The aim of this study was to investigate the predilection site and survival of HPV-related compared to non HPV-related vulvar SCCs.
Data of all consecutive patients with primary vulvar SCC treated at the Department of Gynaecologic Oncology at the Radboud university medical center are prospectively stored in a database: data of patients who have been treated between March 1988 and January 2015 were analyzed. All available histological specimens were tested for HPV with the SPF10/DEIA/LiPA25 system assay and p16INK4a immunohistochemical staining was performed using CINtec® histology kit. Vulvar SCCs were considered HPV-related in case of either >25% p16INK4a expression and HPV positive or >25% p16INK4a expression, and HSIL next to the tumour. The tumour 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.
In total 318 patients were included: 55 (17%) patients had an HPV-related vulvar SCC (Group 1) and 263 (83%) patients had a non HPV-related vulvar SCC (Group 2). The tumours 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 the HPV-related than in the non HPV-related vulvar SCC patients.
HPV-related vulvar SCCs are more frequently located at the perineum and have a favourable prognosis compared to non HPV-related vulvar SCCs. Both localization of the tumour and the HPV-related pathway could explain the favourable prognosis. HPV-related vulvar malignancies seem to be a separate entity within vulvar SCC.