Vulvar squamous cell carcinoma (VSCC) can arise due to three distinct etiological pathways, each with differential clinical prognosis: driven by classical oncogenic mutations in TP53 (HPV−p53mut VSCC, poorest clinical outcome), driven by other somatic oncogenic mutations (HPV−p53wt, intermediate clinical outcome) or driven by a persistent infection with the oncogenic human papillomavirus (HPV+ VSCC, best clinical outcome) [1, 2]. This evidence concerns the gene TP53 and vulvar squamous cell carcinoma.