Many women with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2) are managed expectantly, because about half of them will regress spontaneously, thus avoiding systematic loop electrosurgical excision procedure and related adverse effects. However, most of the guidelines have restricted this strategy to the youngest women. The objectives of our study were to determine the rate and the predictors of regression of HSIL/CIN2 managed expectantly. This retrospective study included 128 patients under 40 years of age (median 29, range 21-39), and HSIL/CIN2 diagnosed by biopsy between 2012 and 2019. They were followed-up without treatment in the department of gynecology at Bordeaux University Hospital, France. The regression of HSIL/CIN2 was defined by the regression or the disappearance of initial colposcopic findings, cytological and/or histological results. The lesion spontaneously regressed or disappeared in 76 (59%) patients during a median follow-up of 25 months (range, 7-86). In the multivariable analysis, minor change at colposcopy (odds ratio OR = 2.8 (CI95% 1.2-6.9), P = 0.02), low grade lesions (ASC-US/LSIL) by cytology (OR = 4.1 (CI95% 1.7-10.1), P < 0.001), and infection by HPV other than HPV-16 (OR = 5.4 (CI95% 2.3-13.9), P < 0.001) predicted the spontaneous regression of HSIL/CIN2. Colposcopic findings, cytological results, and HPV genotyping, but not the age, were baseline factors predicting the evolution of HSIL/CIN2 in patients under 40.Read less <