Efficacy and safety of beta carotones in treatment of oral leukoplakia: systematic review and meta-analysis.

  • Rania Hassan Shalaby Faculty of dentistry, Fayoum University, Egypt.
  • Yehia Fathi Faculty of Medicine and Dentistry, University of Alberta, Canada.
  • Basma Elsaadany Faculty of dentistry, Cairo University, Egypt.

Abstract

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study’s selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.

References

1. Van der Waal I. Oral potentially malignant disorders: Is malignant transformation predictable and preventable?. Med Oral Patol Oral Cir Bucal. 2014;19(4):1–5.
2. Warnakulasuriya S, Johnson NW, Van Der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007; 36(10):575–80.
3. Femiano F, Gombos F, Scully C, Battista C, Belnome G, Esposito V. Oral leukoplakia: open trial of topical therapy with calcipotriol compared with tretinoin. Int J Oral Maxillofac Surg. 2001;30(5):402–6.
4. Vladimirov BS, Schiodt M. The effect of quitting smoking on the risk of unfavorable events after surgical treatment of oral potentially malignant lesions. Int J Oral Maxillofac Surg. 2009;38(11):1188–93.
5. Garewal HS. Beta-carotene and vitamin E in oral cancer prevention. J Cell Biochem Suppl. 1993;17F:262–9.
6. Britton G. Structure and properties of carotenoids in relation to functionitle. FASEB J. 1995;9(15):1551–8.
7. Krinsky NI. Mechanism of action of biological antioxidants. Proc Soc Exp Biol Med. 1992;200:248–54.
8. Kaugars GE, Silverman S, Lovas JG, Brandt RB, Riley WT, Dao Q, et al. A clinical trial of antioxidant supplements in the treatment of oral leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol. 1994; 78(4):462-8.
9. Kaugars GE, Silverman S, Lovas JG, Thompson JS, Brandt RB, Singh VN. Use of antioxidant supplements in the treatment of human oral leukoplakia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81(1):5–14.
10. Liede K, Hietanen J, Saxen L, Haukka J, Timonen T, Häyrinen-Immonen R, Heinonen OP. Long-term supple-mentation with alpha-tocopherol and beta-carotene and prevalence of oral mucosal lesions in smokers. Oral Dis. 1998;4(2):78–83.
11. Erhardt JG, Mack H, Sobeck U, Biesalski HK. beta-Carotene and alpha-tocopherol concentration and antioxidant status in buccal mucosal cells and plasma after oral supplementation. Br J Nutr. 2002;87(5):471–5.
12. Mayne ST. Beta-carotene, carotenoids, and disease prevention in humans. FASEB J. 1996;10(7):690–701.
13. Shah JP, Strong EW, DeCosse JJ, Itri L, Sellers P. Effect of retinoids on oral leukoplakia. Am J Surg. 1983;146(4):466–70.
14. Hong WK Itri LM, Doos W, Batsakis JG, Bell R, Fofonoff S, Byers R, Atkinson EN, Vaughan C EJ. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986; 1501.
15. Garewal HS, Meyskens FL Jr, Killen D, Reeves D, Kiersch TA, Elletson H, Strosberg A, King D, Steinbronn K. Response of Oral Leukoplakia to Beta-Carotene. J Clin Oncol. 1990;8(10):1715–20.
16. Garewal HS, Katz RV, Meyskens F, Pitcock J, Morse D, Friedman S, Peng Y, Pendrys DG, Mayne S, Alberts D, Kiersch T. β-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial. Arch Otolaryngol. 1999;125(12):1305–10.
17. Lee JJ, Hong WK, Hittelman WN, Mao L, Lotan R, Shin DM, Benner SE, Xu XC, Lee JS, Papadimitrakopoulou VM, Geyer C, Perez C, Martin JW, El-Naggar AK, Lippman SM. Predicting Cancer Development in Oral Leukoplakia : Ten Years of Translational Research Predicting Cancer Development in Oral Leukoplakia . Clin Cancer Res. 2000; 6:1702–10.
18. Lippman SM, Batsakis JG, Toth BB, Weber RS, Lee JJ, Martin JW, Hays GL, Goepfert H, Hong WK. Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med. 1993;328(1):15–20.
19. Toma S, Benso S, Albanese E, Palumbo R, Cantoni E, Nicolò G, Mangiante P. Treatment of oral leukoplakia with beta-carotene. Oncology. 1992;49(2):77-81.
20. Malaker K, Anderson BJ, Beecroft WA, Hodson DI. Management of oral mucosal dysplasia with beta-carotene retinoic acid: a pilot cross-over study. Cancer Detect Prev. 1991;15(5):335–40.
21. Stich HF, Rosin MP, Hornby AP, Mathew B, Sankaranarayanan R, Nair MK. Remission of oral leukoplakias and micronuclei in tobacco/betel quid chewers treated with beta-carotene and with beta-carotene plus vitamin a. Int J Cancer. 1988;42(2):195–9.
22. Sankaranarayanan R, Mathew B, Varghese C, Sudhakaran PR, Menon V, Jayadeep A, Nair MK, Mathews C, Mahalingam TR, Balaram P, Nair PP. Papers Chemoprevention of Oral Leukoplakia with Beta Carotene : an Assessment Vitamin A and. Oral Oncol. 1997;33(4):231–6.
23. Nagao T, Warnakulasuriya S, Nakamura T, Kato S, Yamamoto K, Fukano H. and vitamin C supplements : A rando-mized controlled trial. Int J Cancer. 2015;136(7):1708–17.
24. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011.
25. Feller L, Lemmer J. Oral leukoplakia as it relates to HPV infection: A review. Int J Dent. 2012;2012.
26. Lodi G, Franchini R, Warnakulasuriya S, Varoni EM, Sardella A, Kerr AR, Carrassi A, MacDonald LC, Worthington HV. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane database Syst Rev . 2016;7(7):CD001829.
27. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia - A systematic review and meta-analysis. Head Neck. 2009;31(12):1600–9.
28. Rodriguez-Archilla A, Palma-Morales M. Chemoprevention Therapy for Oral Leukoplakia. Clinical Trials and Drug Interactions 2018; 1(1): 1-10
29. Reibel J. Prognosis of oral premalignant lesions: significance of clinical, histopathological, and molecular biological characteristics. Crit Rev Oral Biol Med. 2003;14(1):47–62.
30. Garewal HS. Beta-carotene and vitamin E in oral cancer prevention. J Cell Biochem Suppl. 1993;17F(1 993):262–9.
Published
2019-12-31
How to Cite
SHALABY, Rania Hassan; FATHI, Yehia; ELSAADANY, Basma. Efficacy and safety of beta carotones in treatment of oral leukoplakia: systematic review and meta-analysis.. Journal of Oral Research, [S.l.], v. 8, n. 6, p. 488-498, dec. 2019. ISSN 0719-2479. Available at: <https://www.joralres.com/index.php/JOralRes/article/view/joralres.2019.071>. Date accessed: 26 apr. 2024. doi: https://doi.org/10.17126/joralres.2019.071.
Section
Articles