Objective: To analyze the course of p16/Ki-67-positive abnormal cytological cervical findings and high risk (hr)-HPV- and p16/Ki-67-clearances in women treated with a vaginal gel. Methods: 172 women with a histological diagnosis of CIN2 or p16-positive CIN1 lesions were selected based on a positive cytological p16/Ki-67 test. For 3 months, 75 patients in the active arm (AA) daily administered 5 ml of a vaginal gel. Ninety seven patients in the control arm (CA) underwent no treatment ("watchful waiting"). Endpoints were cytological evolution, p16/Ki-67- and hr-HPV-clearances. Results: At 3 months, cytological regression was observed in 76% (57/75) of patients in the AA compared with 25% (24/97) in the CA. Progression occurred in 5% (4/75) of the AA compared with 15% (15/97) of the CA. The p16/Ki-67 status change was statistically significantly (p < 0.001) in favor of the AA: 77% (58/75) became negative compared to 21% (20/97) in the CA. hr-HPV prevalence decreased significantly (p < 0.001) in the AA from 87 to 44%, while increasing in the CA from 78 to 84%. Cytological regression and p16/Ki-67 changes persisted in the AA at 6 months. Conclusions: The vaginal gel significantly cleared hr-HPV and p16/Ki-67 and was associated with improved cytological findings, thereby potentially offering an effective option against oncogenic risk. Clinical Trial Registration: Identifier: [ISRCTN11009040].

• Klíčová slova
• abnormal cervical smear findings, adsorptive and antioxidative vaginal gel, cervical intraepithelial neoplasia, high risk HPV, p16/Ki-67 biomarker, silicon dioxide, sodium selenite, tumor environment,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

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.

• Klíčová slova
• Cervical intraepithelial neoplasia, HPV, Non-surgical treatment, Silicon dioxide, Sodium selenite, p16/Ki-67 dual staining,
• MeSH
• antigen Ki-67 účinky léků   MeSH
• antioxidancia aplikace a dávkování   MeSH
• aplikace intravaginální MeSH
• cytodiagnostika MeSH
• dospělí MeSH
• dysplazie děložního hrdla patologie   terapie   MeSH
• geny p16 MeSH
• infekce papilomavirem terapie   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy účinky léků   MeSH
• kolposkopie MeSH
• kyselina citronová aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory děložního čípku prevence a kontrola   MeSH
• oxid křemičitý aplikace a dávkování   MeSH
• seleničitan sodný aplikace a dávkování   MeSH
• těhotenství MeSH
• vaginální krémy, pěny a želé * MeSH
• vaginální stěr MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antigen Ki-67 MeSH
• antioxidancia MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• kyselina citronová MeSH
• nádorové biomarkery MeSH
• oxid křemičitý MeSH
• seleničitan sodný MeSH
• vaginální krémy, pěny a želé * MeSH