HPV-independent Precursors Mimicking High-grade Squamous Intraepithelial Lesions (HSIL) of the Vulva
Natalia Rakislova, Laia Alemany, Omar Clavero, Marta del Pino, Adela Saco, Lorena Marimón, Beatriz Quirós, Belén Lloveras, Inmaculada Ribera‐Cortada, María Alejo, Michael Pawlita, Wim Quint, Silvia de Sanjosé, Jaume Ordï
Abstract
Two etiopathogenic types of vulvar squamous cell carcinoma (VSCC) have been described: human papillomavirus (HPV)-associated and HPV-independent. Precursor lesions, frequently identified in the adjacent skin, are also distinct in the 2 types of VSCC: high-grade squamous intraepithelial lesions (HSILs) in HPV-associated VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) or vulvar acanthosis with altered differentiation in HPV-independent VSCC. Although HPV-independent precursors mimicking HSIL have been described in the vulva, their frequency and morphologic spectrum have not been completely characterized. We explored, in a large series of HPV-independent VSSC, the frequency and the histologic features of precursors mimicking HSIL. We included 779 DNA HPV-negative/p16-negative VSCC with at least 1 cm of adjacent skin. We evaluated the histologic and immunohistochemical (p16 and p53) characteristics of the intraepithelial lesions, focusing on precursors mimicking HPV-associated vulvar HSIL. A total of 254 tumors (33%) had adjacent premalignant lesions. Of them, 186 (73%) had dVIN, 22 (9%) had vulvar acanthosis with altered differentiation, and 46 (18%) had lesions that mimicked HSIL. The mean age of the patients with these HSIL-like lesions was 72±15 years. Twenty-six of these HSIL-like lesions had basaloid morphology, 13 warty, and 7 mixed basaloid/warty features. All the HSIL-like precursors were DNA HPV-negative/p16-negative; 74% of them showed p53 abnormal staining and 35% of them had areas of conventional dVIN. In conclusion, about one fifth of the HPV-independent precursors mimic HSIL, showing either basaloid or warty features. Older age and the presence of areas of typical HPV-independent intraepithelial lesions, together with p16 negativity, should raise suspicion of an HPV-independent etiology.