LAUSR

Simple Summary We aimed to systematically review current literature on the risk of developing vulvar squamous cell carcinoma in patients with differentiated vulvar intraepithelial neoplasia. Amongst clinicians, this latter entity is known as a rare premalignant vulvar lesion, which is often found adjacent to vulvar cancer. Knowledge on the exact cancer risk in differentiated vulvar intraepithelial neoplasia can help guide clinicians in the treatment and surveillance of these patients. This review confirms that patients with differentiated vulvar intraepithelial neoplasia have a high risk of developing vulvar squamous cell carcinoma and that cancer progression can occur rapidly. The results of this study highlight the importance of clinical awareness and prompt identification of differentiated vulvar intraepithelial neoplasia, given its high malignant potential. Therefore, further research on this disease should be encouraged. Abstract Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC). Given the rare incidence of dVIN, limited information on the exact cancer risk is available. We systematically reviewed the primary and recurrent VSCC risk in patients with dVIN, as well as the time to cancer development. A systematic search was performed up to July 2021 according to the PRISMA guidelines. Five reviewers independently screened articles on title, abstract and full text, followed by critical appraisal of selected articles using the Quality in Prognostic Studies (QUIPS) tool. Of the 455 screened articles, 7 were included for analysis. The absolute risk for primary VSCC in dVIN varied between 33 and 86%, with a median time to progression to VSCC of 9–23 months. The risk of developing recurrent VSCC in dVIN associated VSCC was 32–94%, with a median time to recurrence of 13–32 months. In conclusion, patients with dVIN have a high risk of developing primary and recurrent VSCC with a short time to cancer progression. Increased awareness, timely recognition, aggressive treatment and close follow-up of HPV-independent vulvar conditions including dVIN is therefore strongly recommended.