An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1

Attila Louis Major, Ales Skřivánek, Etienne Marc Grandjean, Vladimír Dvořák, Tomáš Malík, Marek Pluta, Ivanna Mayboroda, Attila Louis Major, Ales Skřivánek, Etienne Marc Grandjean, Vladimír Dvořák, Tomáš Malík, Marek Pluta, Ivanna Mayboroda

Abstract

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].

Keywords: 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.

Conflict of interest statement

EMG was employed by company Phidalsa Pharma Consultants, Geneva, and by Camara & Partners Consultancy, Nyon, Switzerland. EMG and ALM have received fees for consulting and for redaction of the protocol draft from DEFLAMED International s.r.o. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Major, Skřivánek, Grandjean, Dvořák, Malík, Pluta and Mayboroda.

Figures

Figure 1
Figure 1
Consort flow diagram showing the participant flow of the 172 patients with p16/Ki-67-positive CIN1 and CIN2. ITT, Intention-to-treat population.
Figure 2
Figure 2
Correlation of high-risk HPV and p16/Ki-67 at baseline, 3 and 6 months in the active arm with vaginal gel vs. the control arm.
Figure 3
Figure 3
The evolution of Low-Risk (ASC-US & LSIL)* and High-Risk (ASC-H & HSIL)** patients at 3 and 6 months and the course of p16/Ki-67-positive and negative findings. *ASC-US: Atypical squamous cells of Undetermined significance; LSIL, Low grade squamous intraepithelial lesion. **ASC-H, Atypical Squamous Cells cannot exclude HSIL; HSIL, High-grade squamous intraepithelial lesion. n = number of patients (% of patients). Due to rounding, numbers presented may not add up precisely to the totals provided.

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