Recurrence in High-grade Vulvar Intraepithelial Neoplasia: A Comprehensive Cohort Analysis

OBJECTIVES: High-grade vulvar intraepithelial neoplasia (VIN) is the precursor of vulvar squamous cell carcinoma (VSCC). High-grade VIN is categorized into human papillomavirus (HPV)-associated high-grade squamous intraepithelial lesion (HSIL) and HPV-independent VIN (HPVi-VIN). This study aimed to comprehensively characterize recurrence in a large VIN cohort with long-term follow-up. METHODS: Recurrence was assessed in 578 HSIL and 46 HPVi-VIN patients by evaluating recurrence risk, number of recurrences, and related diagnostic/excisional procedures. Kaplan-Meier analysis estimated recurrence and VSCC risks, and Cox regression analysis was applied to identify risk factors for recurrence. RESULTS: The median follow-up time was 15 years for HSIL and 5.5 years for HPVi-VIN patients. Recurrence occurred in 50% of HSIL (288/578) and 63% of HPVi-VIN (29/46) patients. Cancer was present at first recurrence in 8.0% of HSIL (23/288) and 45% of HPVi-VIN (13/29). The 5-year recurrence risk was 36% for HSIL and 57% for HPVi-VIN (73% for p53 mutant, 25% for p53 wild-type). Among patients with recurrence, 39% of HSIL and 14% of HPVi-VIN had ≥3 recurrences during follow-up, requiring a median of 6.0 and 5.5 surgical procedures, respectively. For HSIL patients, the 5-year recurrence risk increased to 55% and 57% after the first and second recurrence, respectively, while the 5-year cancer risk increased from 4.5% at initial presentation to 7.4% and 12%, respectively. No independent risk factors for recurrence in HSIL were identified. CONCLUSIONS: Both HSIL and HPVi-VIN patients are at high risk of recurrence, with a higher cancer risk observed in those with recurrent HSIL or those with HPVi-VIN.