Vulvar Squamous Cell Carcinoma: A Retrospective Analysis of Epidemiologic Characteristics, HPV Status, and Surgical Outcomes in 35 Cases

<b>Background:</b> Vulvar squamous cell carcinoma (VSCC) is an uncommon yet increasingly relevant malignancy characterized by two distinct etiopathogenetic pathways: HPV-associated and HPV-independent. Data from Eastern Europe remain scarce, where demographic and diagnostic variability may influence disease presentation and outcomes. <b>Purpose:</b> This study aimed to assess the epidemiologic characteristics, HPV status, surgical management, and postoperative morbidity of VSCC in a Romanian single-center cohort, providing real-world evidence from an underrepresented region. <b>Methods:</b> A retrospective analysis was conducted on all 35 consecutive patients with histologically confirmed vulvar squamous cell carcinoma (VSCC) diagnosed and treated between January 2017 and December 2024 at the Department of Obstetrics and Gynecology, County Emergency Clinical Hospital of Craiova, Romania. Demographic, histopathologic, and surgical data were reviewed. HPV genotyping was performed on formalin-fixed paraffin-embedded (FFPE) tissue using PCR-based methods. <b>Results:</b> HPV DNA was detected in 31.4% of cases, predominantly genotypes 16, 18, and 33. HPV-positive patients were significantly younger than HPV-negative ones (median 58 vs. 72.5 years, <i>p</i> < 0.001), supporting the dual-pathway model of carcinogenesis. Early postoperative complications occurred in 65.7% of patients and late morbidity in 71.4%, secondary lymphedema. Surgical radicality was not significantly associated with early complications or length of hospitalization. <b>Conclusions:</b> This study highlights the epidemiologic and surgical patterns of VSCC in an Eastern European population, showing that conservative surgical strategies can maintain oncologic safety while reducing morbidity. These findings emphasize the need for standardized HPV testing, optimized perioperative care, and improved surveillance programs to enhance outcomes and survivorship.