PURPOSE: The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. METHODS: 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. RESULTS: Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. CONCLUSION: SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. TRIAL REGISTRATION NUMBER: ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

• Keywords
• Cervical intraepithelial neoplasia, HPV, Non-surgical treatment, Silicon dioxide, Sodium selenite, p16/Ki-67 dual staining,
• MeSH
• Ki-67 Antigen drug effects   MeSH
• Antioxidants administration & dosage   MeSH
• Administration, Intravaginal MeSH
• Cytodiagnosis MeSH
• Adult MeSH
• Uterine Cervical Dysplasia pathology   therapy   MeSH
• Genes, p16 MeSH
• Papillomavirus Infections therapy   virology   MeSH
• Cyclin-Dependent Kinase Inhibitor p16 drug effects   MeSH
• Colposcopy MeSH
• Citric Acid administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor analysis   MeSH
• Uterine Cervical Neoplasms prevention & control   MeSH
• Silicon Dioxide administration & dosage   MeSH
• Sodium Selenite administration & dosage   MeSH
• Pregnancy MeSH
• Vaginal Creams, Foams, and Jellies * MeSH
• Vaginal Smears MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Ki-67 Antigen MeSH
• Antioxidants MeSH
• Cyclin-Dependent Kinase Inhibitor p16 MeSH
• Citric Acid MeSH
• Biomarkers, Tumor MeSH
• Silicon Dioxide MeSH
• Sodium Selenite MeSH
• Vaginal Creams, Foams, and Jellies * MeSH