Abstract
Vulvar cancer, a rare gynecological malignancy, accounts for 3-5% of cases and is most commonly squamous cell carcinoma. Prognosis is poorer in cancers unrelated to human papillomavirus (HPV), often associated with chronic inflammation. We report the case of a 42-year-old woman from São Paulo, Brazil, who presented with a vulvar lesion initially misdiagnosed as an ingrown hair. Despite treatment, the lesion progressed, and subsequent evaluation revealed invasive squamous cell carcinoma. Biopsy confirmed HPV-independent disease, with immunohistochemistry demonstrating aberrant p53 expression. Molecular analysis identified differentiated vulvar intraepithelial neoplasia, underscoring the distinct molecular pathways of HPV-related and HPV-independent carcinogenesis. This case emphasizes the importance of early diagnosis, comprehensive histopathological assessment, and further research to improve management and outcomes in HPV-independent vulvar cancer.