Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type

Abstract

The distinct histopathogenetic pathways of vulvar squamous cell neoplasia have led to a shift from a morphology-based to an etiology/molecular-based histopathologic classification, adopted in the most recent WHO Classification of Female Genital Tumours. There are two main categories: HPV-associated (HPVa) and HPV-independent (HPVi) vulvar squamous neoplasia. Most HPVi VSCCs have an underlying TP53 mutation, but attention has recently focused on the uncommon third molecular subtype: TP53 wild-type HPVi VSCC. We review this shift to the etiology/molecular-based classification of VSCC, emphasizing the diagnostic and treatment implications of this change and highlighting the third molecular subtype.