DOI QR코드

DOI QR Code

Clearance of Cervical Human Papillomavirus Infection by Topical Application of Curcumin and Curcumin Containing Polyherbal Cream: A Phase II Randomized Controlled Study

  • Basu, Partha (Department of Gynecological Oncology, Chittaranjan National Cancer Institute) ;
  • Dutta, Sankhadeep (Department of Oncogene Regulation, Chittaranjan National Cancer Institute) ;
  • Begum, Rakiba (Department of Gynecological Oncology, Chittaranjan National Cancer Institute) ;
  • Mittal, Srabani (Department of Gynecological Oncology, Chittaranjan National Cancer Institute) ;
  • Dutta, Paromita Das (Department of Dietetics and Nutrition, Chittaranjan National Cancer Institute) ;
  • Bharti, Alok Chandra (Institute of Cytology and Preventive Oncology, NOIDA) ;
  • Panda, Chinmay Kumar (Department of Oncogene Regulation, Chittaranjan National Cancer Institute) ;
  • Biswas, Jaydip (Chittaranjan National Cancer Institute) ;
  • Dey, Bindu (Department of Biotechnology, Ministry of Science and Technology, Government of India) ;
  • Talwar, Gursaran Prashad (Talwar Research Foundation) ;
  • Das, Bhudev Chandra (Dr. BR Ambedkar Center for Biomedical Research)
  • Published : 2013.10.30

Abstract

Curcumin and curcumin containing polyherbal preparations have demonstrated anti-microbial and antiviral properties in pre-clinical studies. Till date no therapeutic intervention has been proved to be effective and safe in clearing established cervical human papillomavirus (HPV) infection. The present study evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA test by PCR. HPV positive women without high grade cervical neoplasias (N=287) were randomized to four intervention arms to be treated with vaginal Basant cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal capsules respectively. All subjects were instructed to use one application of the assigned formulation daily for 30 consecutive days except during menstruation and recalled within seven days of the last application for repeat HPV test, cytology and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance (81.3%) than placebo though the difference was not statistically significant. Vaginal irritation and itching, mostly mild to moderate, was significantly higher after Basant application. No serious adverse events were noted.

Keywords

References

  1. Beutner KR, Spruance SL, Hougham AJ, et al (1998). Treatment of genital warts with an immuneresponse modifier (imiquimod). J Am Acad Dermatol, 38, 230-9. https://doi.org/10.1016/S0190-9622(98)70243-9
  2. Bharti AC, Shukla S, Mahata S, Hedau S, Das BC (2009). Antihuman papillomavirus therapeutics: facts and future. Ind J Med Res, 130, 296-310.
  3. Divya CS, Pillai MR (2006). Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog, 45, 320-32. https://doi.org/10.1002/mc.20170
  4. Dutta S, Begum R, Mazumder D, et al (2012). Prevalence of human papillomavirus in women without cervical cancer: a population-based study in Eastern India. Int J Gynecol Pathol, 31, 178-83.
  5. Grimm C, Polterauer S, Natter C, et al (2012). Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol, 120, 152-9. https://doi.org/10.1097/AOG.0b013e31825bc6e8
  6. Gupta N, Gupta SK (2011). Microbicides: a new hope for HIV prevention. Ind J Med Res, 134, 939-49. https://doi.org/10.4103/0971-5916.92639
  7. Khan MJ, Castle PE , Lorincz AT, et al (2005). The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. JNCI, 97, 1072-9. https://doi.org/10.1093/jnci/dji187
  8. Kjaer SK, van den Brule AJ, Paull G, et al (2002). Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ, 325, 572-8. https://doi.org/10.1136/bmj.325.7364.572
  9. Maher DM, Bell MC, O'Donnell EA, et al (2011). Curcumin suppresses human papillomavirus oncoproteins, restores p53, Rb, and PTPN13 proteins and inhibits benzo[a]pyrene-induced upregulation of HPV E7. Mol Carcinog, 50, 47-57. https://doi.org/10.1002/mc.20695
  10. Molano M, van den Brule A, Plummer M, et al (2003). Determinants of Clearance of Human Papillomavirus Infections in Colombian Women with Normal Cytology: A Population-based, 5-Year Follow-up Study. Am J Epidemiol, 158, 486-94. https://doi.org/10.1093/aje/kwg171
  11. Sterling JC, Handfield-Jones S, Hudson P (2001). Guidelines for the management of cutaneous warts. Br J Dermatol, 144, 4-11 https://doi.org/10.1046/j.1365-2133.2001.04066.x
  12. Talwar GP, Dar SA, Rai MK, et al (2008). A novel polyherbal microbicide with inhibitory effect on bacterial, fungal and viral genital pathogens, Int J Antimicrob Agents, 32, 180-5. https://doi.org/10.1016/j.ijantimicag.2008.03.004
  13. Talwar GP, Raghuvanshi P, Mishra R, et al (2000). Polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens. Am J Rep Immunol, 43, 144-51. https://doi.org/10.1111/j.8755-8920.2000.430303.x
  14. van Duin M, Snijders PJ, Schrijnemakers HF, et al (2002). Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance. Int J Cancer, 98, 590-5 https://doi.org/10.1002/ijc.10232
  15. Vermani K, Garg S (2002). Herbal medicines for sexually transmitted diseases and AIDS, J Ethnopharmacol, 80, 49-66. https://doi.org/10.1016/S0378-8741(02)00009-0

Cited by

  1. Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells vol.15, pp.3, 2014, https://doi.org/10.7314/APJCP.2014.15.3.1403
  2. Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3851
  3. An update on Curcuma as a functional food in the control of cancer and inflammation vol.18, pp.6, 2015, https://doi.org/10.1097/MCO.0000000000000227
  4. An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia vol.24, pp.12, 2015, https://doi.org/10.1517/13543784.2015.1099628
  5. Persistent HPV16/18 infection in Indian women with the A-allele (rs6457617) of HLA-DQB1 and T-allele (rs16944) of IL-1β −511 is associated with development of cervical carcinoma vol.64, pp.7, 2015, https://doi.org/10.1007/s00262-015-1693-5
  6. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases vol.174, pp.11, 2017, https://doi.org/10.1111/bph.13621
  7. The Role of Natural Polyphenols in the Prevention and Treatment of Cervical Cancer—An Overview vol.21, pp.8, 2016, https://doi.org/10.3390/molecules21081055
  8. Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features vol.43, pp.3, 2016, https://doi.org/10.1002/biof.1344
  9. From Bench to Bedside: Converting Placebo Research into Belief Activation vol.23, pp.8, 2017, https://doi.org/10.1089/acm.2016.0375
  10. Mechanisms and therapeutic prospects of polyphenols as modulators of the aryl hydrocarbon receptor vol.8, pp.4, 2017, https://doi.org/10.1039/C6FO01810F
  11. Curcumin as an anti-human papillomavirus and anti-cancer compound vol.11, pp.18, 2015, https://doi.org/10.2217/fon.15.166
  12. in patients with cervicovaginal human papillomavirus infection: A randomized, double-blind, placebo trial vol.32, pp.10, 2018, https://doi.org/10.1002/ptr.6131
  13. Effectiveness of Curcumin for Treating Cancer During Chemotherapy vol.24, pp.1, 2018, https://doi.org/10.1089/act.2017.29147.yhk
  14. Curcumin as a therapeutic agent in leukemia pp.00219541, 2019, https://doi.org/10.1002/jcp.28072
  15. Gene Expression pp.1532-7914, 2019, https://doi.org/10.1080/01635581.2018.1559934