Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

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

Abstract

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.

Conflict of interest statement

ALM and EMG have received fees for consulting and for redaction of the protocol draft from DEFLAMED International s.r.o., Prague Czech Republic. ALM has received speaking honoraria and JS honoraria for study coordination and monitoring from the sponsor of the study. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram
Fig. 2
Fig. 2
Difference in cytological findings after 6 months in the active and control arms

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