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Experience of clinical use of diindolylmethane in the treatment of HPV-associated low-grade cervical lesions

https://doi.org/10.21518/2079-701X-2020-3-25-31

Abstract

Introduction. A genital human papillomavirus infection receives the sword-point attention of both researchers and practitioners, due to its large prevalence in the human population, high contagiousness and, in particular, the ability of some HPV strains to contribute to the development of malignancy. This is particularly so with cervical cancer (CC), one of the most common types of cancer both in the Russian Federation and most countries of the world. It ranked first among the causes of malignant tumour deaths of women aged over 30 years. Objective. To present the experience in using the 3,3’-diindolylmethane-containing drug in the treatment of patients with HPVassociated low-grade cervical intraepithelial lesion. Material and methods. 62 women with HPV-associated low-grade cervical intraepithelial lesion were examined and received treatment with the 3,3’-diindolylmethane-containing drug (Cervicon-DIM). The primary diagnosis and therapeutic outcomes monitoring included the following research methods: colposcopy, histological examination of biopsy cervical specimens, Pap test, RT-PCR of high carcinogenic risk (HCR) HPV. The therapy compliance was evaluated using the clinical psychological test method (Morisky Green scale): compliant patients 4 scores (noncompliant 2 scores or less, insufficiently compliant 3 scores). Results. The therapeutic outcomes using 3,3’-diindolylmethane-containing drug (Cervicon-DIM) in the form of vaginal suppositories (100 mg twice daily for 90 days) showed clinical (recovery of colposcopic status in 83.0% of patients), cytological (confirmed absence of LSIL in 98.3% of women) and microbiological (PCR-negative HCR HPV in 91.5% of women) efficacy with satisfactory tolerance of the drug. Сonclusions. The therapeutic outcomes obtained using 3,3’-diindolylmethane-containing drug in the treatment of patients with HPV-associated low-grade cervical intraepithelial lesion could be considered as satisfactory. The data presented may be of interest to practicing gynecologists and other specialists.

About the Authors

I. I. Kutsenko
Kuban State Medical University
Russian Federation

Irina I. Kutsenko, Dr. of Sci. (Med.), professor, Head of Department of Obstetrics and Gynecology

 



I. O. Borovikov
Kuban State Medical University
Russian Federation

Igor O. Borovikov, Dr. of Sci. (Med.), Associate Professor, Department of Obstetrics, Gynecology and Perinatology

4, Sedina St., Krasnodar, 350063



H. I. Gorring
Kuban State Medical University
Russian Federation

Hava I. Gorring, Graduate student, Department of Obstetrics and Gynecology

4, Sedina St., Krasnodar, 350063



A. S. Magay
Kuban State Medical University
Russian Federation

Anton S. Magay, Senior laboratory, Department of Obstetrics and Gynecology

4, Sedina St., Krasnodar, 350063



A. A. Gorbulina
Kuban State Medical University
Russian Federation

Anastasia A. Gorbulina, sixth-year student of the Faculty of Medicine

4, Sedina St., Krasnodar, 350063



References

1. Kaprin A.D., Starinskiy V.V., Petrova G.V. (ed.). Malignant neoplasms in Russia in 2012 (morbidity and mortality). M.: Hertsen Moscow Research Institute of Oncology of the Ministry of Health of Russia; 2014; 250 p. (In Russ.) Available at: https://elibrary.ru/item.asp?id=24071556.

2. Vinokurova S.V. Genetic and epigenetic mechanisms of regulation of human papillomavirus. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology. 2016;3(2):18-25. (In Russ.) doi: 10.17650/2313805X.2016.3.2.18-25.

3. Bodily J., Laimins L. Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol. 2011;19(1):33–39. doi: 10.1016/j.tim.2010.10.002.

4. Cheng S., Schmidt-Grimminger D., Murant T., Broker T.R., Chow L.T. Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes Dev. 2015;9(19):2335–2349. doi: 10.1101/gad.9.19.2335.

5. Chaiwongkot A., Vinokurova S., Pientong C. et al. Differential methylation of E2 binding sites in episomal and integrated HPV 16 genomes in preinvasive and invasive cervical lesions. Int J Cancer. 2013;132(9):2087–2094. doi: 10.1002/ijc.27906.

6. Mirabello L., Schiffman M., Ghosh A. et al. Elevated methylation of HPV 16 DNA is associated with the development of high grade cervical intraepithelial neoplasia. Int J Cancer. 2013;132(6):1412–1422. doi: 10.1002/ijc.27750.

7. Kajitani N., Satsuka A., Kawate A., Sakai H. Productive lifecycle of human papillomaviruses that depends upon squamous epithelial differentiation. Front Microbiol. 2012;3:152. doi: 10.3389/fmicb.2012.00152.

8. Kiselev V.I., Ashrafyan L.A., Drukh V.M., Muyzhnek E.L., Kuznetsov I.N., Pchelintseva O.I., Andrianova E.A., Baranovskiy P.M. Efficacy of the novel pharmaceutical composition in suppository form comprising DIM in patients with grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). Vestnik Rossiyskogo nauchnogo tsentra rentgenoradiologii = Russian Scientific Center of Roentgenoradiology. 2014;14:1–14. (In Russ.) Available at: http://vestnik.rncrr.ru/vestnik/v14/papers/pchelintseva_v14.pdf.

9. Mezhevitinova E.A., Donnikov A.E., Prilepskaya V.N. Cervical intraepithelial neoplasia. Role of cytokine therapy in treatment efficiency improvement. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie = Obstetrics and Gynecology: News, Opinions, Training. 2019;7(4):66–71. (In Russ.) doi: 10.24411/2303-9698-2019-14005.

10. Borovikov I.O., Kutsenko I.I., Gorring C.I. Experience of using the immunomodulator in the therapy of papillomavirus infection of genitalia in women. Akusherstvo i Ginekologiya = Obstetrics and Gynecology. 2018;(3):122–128. (In Russ.) doi: 10.18565/aig.2018.3.122-128.

11. Abakarova P.R., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E. Local cytokine therapy in a comprehensive treatment of HPV-associated cervical diseases. Ginekologiya = Gynecology. 2019;21(1):28–32. (In Russ.) doi: 10.26442/20795696.2019.1.190284.

12. Dolgushina V.F., Akhmatova A.N., Telesheva L.F., Abramovskikh O.S. Persistence of papillomavirus infection in women with chronic cervicitis. Ural'skiy meditsinskiy zhurnal = Ural Medical Journal. 2010;(3):91–94. (In Russ.) Available at: http://www.fesmu.ru/elib/Article.aspx?id=223369.

13. Abakarova P.R., Prilepskaya V.N. HPV-associated diseases of the cervix. Complex therapy options. Ginekologiya = Gynecology. 2017;19(5):4–9. (In Russ.) doi: 10.26442/2079-5696_19.5.4-9.

14. Prilepskaya V.N., Dovletkhanova E.R. Papillomavirus infection: From early diagnosis to rational therapy. Akusherstvo i Ginekologiya = Obstetrics and Gynecology. 2013;(2):101–107. (In Russ.) Available at: https://aig-journal.ru/articles/Papillomavirusnaya-infekciya-ot-rannei-diagnostiki-k-racionalnoiterapii.html.

15. Tang Y., Zheng L., Yang S., Li B., Su H., Zhang L.P. Epidemiology and genotype distribution of human papillomavirus (HPV) in Southwest China: a cross-sectional five years study in non-vaccinated women. Virol J. 2017;14(1):84. doi: 10.1186/s12985-017-0751-3.

16. Dubrovina S.O., Ardintseva O.A., Krasilnikova L.V. et al. To the question about diagnostics, prevention and therapy of pathology of the cervix. Ginekologiya = Gynecology. 2018;20(5):33–36. (In Russ.) doi: https://doi.org/10.26442/2079-5696_2018.5.33-36

17. Zarochentseva N.V. Dzhidzhikhiya L.K. Cervical intraepithelial neoplasia: a modern view on the problem and solutions. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie = Obstetrics and Gynecology: News, Opinions, Training. 2016;(4):92–101. (In Russ.) Available at: http://www.acu-gin-journal.ru/ru/jarticles_acu/263.html?SSr=5501343b8512ffffffff27c__07e403190c370a-1719.

18. Sepkovic D.W., Stein J., Carlisle A.D., Ksieski H.B., Auborn K., Bradlow H.L. Diindolylmethane inhibits cervical dysplasia, alters estrogen metabolism, and enhances immune response in the K14-HPV16 transgenic mouse model. Cancer Epidemiol Biomarkers Prev. 2009;18(11):2957–2964. doi: 10.1158/1055-9965.EPI-09-0698.

19. Sukhikh G.T., Ashrafyan L.A., Kiselev V.I., Apolikhina I.A., Maltseva L.I., Suturina L.V. et al. Investigation of the efficacy and safety of a diindolylmethanebased drug in patients with cervical intraepithelial neoplasia grades 1-2 (CIN 1-2). Akusherstvo i Ginekologiya = Obstetrics and Gynecology. 2018;(9):91–98. (In Russ.) doi: 10.18565/aig.2018.9.91-98.

20. Beaver L.M., Yu T.W., Sokolowski E.I., Williams D.E., Dashwood R.H., Ho E. 3,3’-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells. Toxicol Appl Pharmacol. 2012;263(3):345–351. doi: 10.1016/j.taap.2012.07.007.

21. Wu T.Y., Khor T.O., Su Z.Y., Saw C.L., et al. Epigenetic modifications of Nrf2 by 3,3’-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. The AAPS J. 2013;15(3):864–874. doi: 10.1208/s12248013-9493-3.

22. Semov A., Iourtchenko L., Liu L., Xu Y., Su X., Muyjnek E., Kiselev V., Alakhov V. Diindolylmethane (DIM) selectively inhibits cancer stem cells. Biochem Biophys Res Commun. 2012;424(1):45–51. doi: 10.1016/j.bbrc.2012.06.062.

23. Morisky D., Green L., Levine D. Concurrent and predictive validity of a selfreported measure of medication adherence. Med Care. 1986;24(1):67–74. doi: 10.1097/00005650-198601000-00007.


Review

For citations:


Kutsenko II, Borovikov IO, Gorring HI, Magay AS, Gorbulina AA. Experience of clinical use of diindolylmethane in the treatment of HPV-associated low-grade cervical lesions. Meditsinskiy sovet = Medical Council. 2020;(3):25-31. (In Russ.) https://doi.org/10.21518/2079-701X-2020-3-25-31

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ISSN 2079-701X (Print)
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