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Background: Recent data have shown that the human papillomavirus (HPV) vaccine could impact on a decrease in high-grade cervical intraepithelial lesions (HSIL) in women who have undergone surgical treatment. This study aimed to evaluate the efficacy of human papilloma virus (HPV) vaccination against persistent/recurrent disease in patients undergoing conization for high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia-grade 2-3 (HSIL/CIN 2-3). Methods: From January 2009 to March 2019, 563 patients with HSIL/CIN 2-3 underwent conization. The population was divided into two groups according to vaccination status: vaccinated-group (V-Group) and non-vaccinated-group (NV-Group). Bivalent or quadrivalent vaccines were administered indiscriminately. A follow-up was scheduled every 6–12 months according to clinical guidelines. The mean follow-up was 29.6 vs. 36.5 months in the V-group and NV-group, respectively. Results: 277 (49.2%) women were vaccinated, while 286 (50.8%) were not. Overall, persistent/recurrent HSIL/CIN 2-3 was presented by 12/277 (4.3%) women in the V-Group and 28/286 (9.8%) in the NV-Group (HR: 0.43, 95% Confidence interval 0.22–0.84, p = 0.014). Vaccination was associated with a 57% reduction in HSIL persistence/recurrence after treatment. When no disease was present in the first 6-month follow-up visit, persistence/recurrence rates were very low in both groups: 1.1% in the V-Group vs. 1.5% in the NV-Group (p &gt; 0.05). The factor associated with a high-risk of HSIL persistence/recurrence was the presentation of a positive co-test in the first control after treatment (p &lt; 0.001). Conclusions: Our results corroborate the benefit of HPV vaccination in woman treated for HSIL/CIN 2-3, showing a reduction of persistent/recurrent HSIL/CIN 2-3.

Effectiveness of Prophylactic Human Papillomavirus Vaccine in the Prevention of Recurrence in Women Conized for HSIL/CIN 2-3: The VENUS Study