Mouthwash use and oral cancer: a systematic review and meta-analysis
DOI:
https://doi.org/10.11606/s1518-8787.2023057004752Palavras-chave:
Mouthwashes, Mouth Neoplasms, Risk Factors, Meta-AnalysisResumo
OBJECTIVE: This study aimed to investigate the effect of mouthwash use on the development of oral cancer. METHODS: Observational studies with adult/older adult populations that have examined the association between mouthwash use and oral cancer were included. Electronic search was performed in July 2022, with no time or language restrictions. PubMed/Medline, Embase, and Web of Science databases were used, and the search was extended to theses and dissertations libraries, Google Scholar, reference lists, and other sources. Methodological quality was assessed using the Newcastle-Ottawa Scale and quantitative data synthesis was performed by random effects meta-analysis, with different subgroup analyses and meta-regression. This revision was registered in Prospero (CRD42020143307). RESULTS: Of the 4,094 studies identified in the search, 15 case-control studies were included in the review, totaling 6,515 cases and 17,037 controls. The meta-analysis included 17 measures of effect from 15 case-control studies. The pooled OR was 1.00 (95%CI: 0.79–1.26, n = 17 studies), but it was 2.58 (95%CI: 1.38–4.82, n = 2 studies) among those who had used mouthwashes three times or more times a day, and 1.30 (95%CI: 1.10–1.54, n = 4 studies) among those who had used mouthwashes for more than 40 years. CONCLUSIONS: We f ound e vidence t hat a h igh f requency o f m outhwash u se m ay b e associated with an increased risk of oral cancer. However, despite the biological plausibility for this association, we suggest caution upon interpretation of our findings due to the few number of studies that have investigated the mouthwash use frequency, which should be considered. Therefore, we recommend that future studies assess, in detail, the frequency, duration, and content of mouthwashes to increase the strength of evidence for a possible dose-response effect of mouthwashes on oral cancer risk.
Referências
Choi SW, Thomson P. Increasing incidence of oral cancer in Hong Kong-Who, where…and why? J Oral Pathol Med. 2019 Jul;48(6):483-90. https://doi.org/10.1111/jop.12868
Fan J, Liu W, Zhang M, Xing C. A literature review and systematic meta-analysis on XRCC3 Thr241Met polymorphism associating with susceptibility of oral cancer. Oncol Lett. 2019 Sep;18(3):3265-73. https://doi.org/10.3892/ol.2019.10609
Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global cancer observatory: cancer today. Lyon, International Agency for Research on Cancer; 2018 [cited 2022 Aug 7]. Available from: https://gco.iarc.fr/today
Cooper JS, Porter K, Mallin K, Hoffman HT, Weber RS, Ang KK, et al. National Cancer Database report on cancer of the head and neck: 10-year update. Head Neck. 2009 Jun;31(6):748-58. https://doi.org/10.1002/hed.21022
Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am. 2015 Jul;24(3):491-508. https://doi.org/10.1016/j.soc.2015.03.006
Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11(1):9-22. https://doi.org/10.1038/nrc2982
Asthana S, Labani S, Kailash U, Sinha DN, Mehrotra R. Association of smokeless tobacco use and oral cancer: a systematic global review and meta-analysis. Nicotine Tob Res. 2019 Aug;21(9):1162-71. https://doi.org/10.1093/ntr/nty074
Gupta B, Johnson NW. Systematic review and meta-analysis of association of smokeless tobacco and of betel quid without tobacco with incidence of oral cancer in South Asia and the Pacific. PLoS One. 2014 Nov;9(11):e113385. https://doi.org/10.1371/journal.pone.0113385
Mello FW, Melo G, Pasetto JJ, Silva CA, Warnakulasuriya S, Rivero ER. The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis. Clin Oral Investig. 2019 Jul;23(7):2849-59. https://doi.org/10.1007/s00784-019-02958-1
Aghiorghiesei O, Zanoaga O, Nutu A, Braicu C, Campian RS, Lucaciu O, et al. The World of Oral Cancer and its risk factors viewed from the aspect of microRNA expression patterns. Genes (Basel). 2022 Mar;13(4):594. https://doi.org/10.3390/genes13040594
Ram H, Sarkar J, Kumar H, Konwar R, Bhatt ML, Mohammad S. Oral cancer: risk factors and molecular pathogenesis. J Maxillofac Oral Surg. 2011 Jun;10(2):132-7. https://doi.org/10.1007/s12663-011-0195-z
Alqahtani WS, Almufareh NA, Al-Johani HA, Alotaibi RK, Juliana CI, Aljarba NH, et al. Oral and oropharyngeal cancers and possible risk factors across gulf cooperation council countries: a systematic review. World J Oncol. 2020 Aug;11(4):173-81.
https://doi.org/10.14740/wjon12
Calderón-Montaño JM, Jiménez-Alonso JJ, Guillén-Mancina E, Burgos-Morón E, López-Lázaro M. A 30-s exposure to ethanol 20% is cytotoxic to human keratinocytes: possible mechanistic link between alcohol-containing mouthwashes and oral cancer. Clin Oral Investig. 2018 Nov;22(8):2943-6. https://doi.org/10.1007/s00784-018-2602-z
Adams D, Addy M. Mouthrinses. Adv Dent Res. 1994 Jul;8(2):291-301. https://doi.org/10.1177/08959374940080022401
Eliot MN, Michaud DS, Langevin SM, McClean MD, Kelsey KT. Periodontal disease and mouthwash use are risk factors for head and neck squamous cell carcinoma. Cancer Causes Control. 2013 Jul;24(7):1315-22. https://doi.org/10.1007/s10552-013-0209-x
La Vecchia C. Mouthwash and oral cancer risk: an update. Oral Oncol. 2009;45(3)(3):198-200. https://doi.org/10.1016/j.oraloncology.2008.08.012
Lachenmeier DW, Gumbel-Mako S, Sohnius EM, Keck-Wilhelm A, Kratz E, Mildau G. Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer. Int J Cancer. 2009 Aug;125(3):730-5. https://doi.org/10.1002/ijc.24381
Lachenmeier DW. Alcohol-containing mouthwash and oral cancer : can epidemiology prove the absence of risk? Ann Agric Environ Med. 2012;19(3):609-10. https://doi.org/10.1002/ptr.4762.15
Lachenmeier DW. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. J Occup Med Toxicol. 2008;3:26. https://doi.org/10.1186/1745-6673-3-26
Poggi P, Rodriguez y Baena R, Rizzo S, Rota MT. Mouthrinses with alcohol: cytotoxic effects on human gingival fibroblasts in vitro. J Periodontol. 2003 May;74(5):623-9. https://doi.org/10.1902/jop.2003.74.5.623
Gagari E, Kabani S. Adverse effects of mouthwash use: review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Oct;80(4):432-9. https://doi.org/10.1016/S1079-2104(05)80337-3
Seitz HK, Matsuzaki S, Yokoyama A, Homann N, Väkeväinen S, Wang XD. Alcohol and cancer In: Verster JC, Brady K, Galanter M, Conrod P, eds. Drug abuse and addiction in medical illness: causes. consequences and treatment. 2001;25(5):137S-43S. https://doi.org/10.1007/978-1-4614-3375-0_35
Guillén-Mancina E, Calderón-Montaño JM, López-Lázaro M. Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption. Drug Alcohol Depend. 2018 Feb;183(183):201-4. https://doi.org/10.1016/j.drugalcdep.2017.11.013
Müller HD, Eick S, Moritz A, Lussi A, Gruber R. Cytotoxicity and Antimicrobial Activity of Oral Rinses In Vitro. BioMed Res Int. 2017;2017:4019723. https://doi.org/10.1155/2017/4019723
Tartaglia GM, Kumar S, Fornari CD, Corti E, Connelly ST. Mouthwashes in the 21st century: a narrative review about active molecules and effectiveness on the periodontal outcomes. Expert Opin Drug Deliv. 2017 Aug;14(8):973-82. https://doi.org/10.1080/17425247.2017.1260118
Vlachojannis C, Al-Ahmad A, Hellwig E, Chrubasik S. Listerine® Products: an update on the efficacy and safety. Phytother Res. 2016 Mar;30(3):367-73. https://doi.org/10.1002/ptr.5555
Sangroula S, Baez Vasquez AY, Raut P, Obeng B, Shim JK, Bagley GD, et al. Triclosan disrupts immune cell function by depressing Ca2+ influx following acidification of the cytoplasm. Toxicol Appl Pharmacol. 2020 Oct;405(June):115205.
https://doi.org/10.1016/j.taap.2020.115205
Ruszkiewicz JA, Li S, Rodriguez MB, Aschner M. Is Triclosan a neurotoxic agent? J Toxicol Environ Health B Crit Rev. 2017;20(2):104-17. https://doi.org/10.1080/10937404.2017.1281181
Fromm-Dornieden C, Rembe JD, Schäfer N, Böhm J, Stuermer EK. Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management - prospects and limitations. J Med Microbiol. 2015 Apr;64(Pt 4):407-14. https://doi.org/10.1099/jmm.0.000034
Coelho AS, Laranjo M, Gonçalves AC, Paula A, Paulo S, Abrantes AM, et al. Cytotoxic effects of a chlorhexidine mouthwash and of an enzymatic mouthwash on human gingival fibroblasts. Odontology. 2020 Apr;108(2):260-70.
https://doi.org/10.1007/s10266-019-00465-z
Karpiński TM, Szkaradkiewicz AK. Chlorhexidine : pharmaco-biological activity and application. Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1321-6. PMID:25912596
Pucher JJ, Daniel JC. The effects of chlorhexidine digluconate on human fibroblasts in vitro. J Periodontol. 1992 Jun;63(6):526-32. https://doi.org/10.1902/jop.1992.63.6.526
Ustrell-Borràs M, Traboulsi-Garet B, Gay-Escoda C. Alcohol-based mouthwash as a risk factor of oral cancer: a systematic review. Med Oral Patol Oral Cir Bucal. 2020 Jan;25(1):e1-12. https://doi.org/10.4317/medoral.23085
Hostiuc S, Ionescu IV, Drima E. Mouthwash use and the risk of oral, pharyngeal, and laryngeal câncer: a meta-analysis. Int J Environ Res Public Health. 2021 Aug;18(15):8215. https://doi.org/10.3390/ijerph18158215
Aceves Argemí R, González Navarro B, Ochoa García-Seisdedos P, Estrugo Devesa A, López-López J. Mouthwash with alcohol and oral carcinogenesis: systematic review and meta-analysis. J Evid Based Dent Pract. 2020 Jun;20(2):101407.
https://doi.org/10.1016/j.jebdp.2020.101407
Gandini S, Negri E, Boffetta P, La Vecchia C, Boyle P. Mouthwash and oral cancer risk quantitative meta-analysis of epidemiologic studies. Ann Agric Environ Med. 2012;19(2):173-80.
Wynder EL, Kabat G, Rosenberg S, Levenstein M. Oral cancer and mouthwash use. J Natl Cancer Inst. 1983 Feb;70(2):255-60.
Kabat GC, Hebert JR, Wynder EL. Risk factors for oral cancer in women. Cancer Res. 1989 May;49(10):2803-6.
Garrote LF, Herrero R, Reyes RM, Vaccarella S, Anta JL, Ferbeye L, et al. Risk factors for cancer of the oral cavity and oro-pharynx in Cuba. Br J Cancer. 2001 Jul;85(1):46-54. https://doi.org/10.1054/bjoc.2000.1825
Winn DM, Diehl SR, Brown LM, Harty LC, Bravo-Otero E, Fraumeni JF Jr, et al. Mouthwash in the etiology of oral cancer in Puerto Rico. Cancer Causes Control. 2001 Jun;12(5):419-29. https://doi.org/10.1023/A:1011291807468
Guha N, Boffetta P, Wünsch Filho V, Eluf Neto J, Shangina O, Zaridze D, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol. 2007 Nov;166(10):1159-73. https://doi.org/10.1093/aje/kwm193
Divaris K, Olshan AF, Smith J, Bell ME, Weissler MC, Funkhouser WK, et al. Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study. Cancer Causes Control. 2010 Apr;21(4):567-75. https://doi.org/10.1007/s10552-009-9486-9
MacFarlane TV., MacFarlane GJ, Oliver RJ, Benhamou S, Bouchardy C, Ahrens W, et al. The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study. Cancer Causes Control. 2010;21(12):2213-2221. https://doi.org/10.1007/s10552-010-9641-3
Ahrens W, Pohlabeln H, Foraita R, Nelis M, Lagiou P, Lagiou A, et al. Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study. Oral Oncol. 2014 Jun;50(6):616-25. https://doi.org/10.1016/j.oraloncology.2014.03.001
Boffetta P, Hayes RB, Sartori S, Lee YC, Muscat J, Olshan A, et al. Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium. Eur J Cancer Prev. 2016 Jul;25(4):344-8. https://doi.org/10.1097/CEJ.0000000000000179
Weaver A, Fleming SM, Smith DB. Mouthwash and oral cancer: carcinogen or coincidence? J Oral Surg. 1979 Apr;37(4):250-3.
Morse DE, Katz RV, Pendrys DG, Holford TR, Krutchkoff DJ, Eisenberg E, et al. Mouthwash use and dentures in relation to oral epithelial dysplasia. Oral Oncol. 1997 Sep;33(5):338-43. https://doi.org/10.1016/S1368-8375(97)00019-5
Marshall JR, Graham S, Haughey BP, Shedd D, O’Shea R, Brasure J, et al. Smoking, alcohol, dentition and diet in the epidemiology of oral cancer. Eur J Cancer B Oral Oncol. 1992 Jul;28B(1):9-15. https://doi.org/10.1016/0964-1955(92)90005-L
Howie NM, Trigkas TK, Cruchley AT, Wertz PW, Squier CA, Williams DM. Short-term exposure to alcohol increases the permeability of human oral mucosa. Oral Dis. 2001 Nov;7(6):349-54. Available from: www.munksgaard.dk
https://doi.org/10.1034/j.1601-0825.2001.00731.x
Mascarenhas AK, Allen CM, Moeschberger ML. The association between Viadent use and oral leukoplakia: results of a matched case-control study. J Public Health Dent. 2002;62(3):158-62. https://doi.org/10.1111/j.1752-7325.2002.tb03437.x
Moazzez R, Thompson H, Palmer RM, Wilson RF, Proctor GB, Wade WG. Effect of rinsing with ethanol-containing mouthrinses on the production of salivary acetaldehyde. Eur J Oral Sci. 2011 Dec;119(6):441-6. https://doi.org/10.1111/j.1600-0722.2011.00886.x
Lachenmeier DW, Monakhova YB. Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism. J Exp Clin Cancer Res. 2011 Jan;30(1):3. https://doi.org/10.1186/1756-9966-30-3
Kocaelli H, Apaydin A, Aydil B, Ayhan M, Karadeniz A, Ozel S, et al. Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects. Hippokratia. 2014;18(3):269-74.
Fox SA, Currie SS, Dalley AJ, Farah CS. Transcriptome changes induced in vitro by alcohol-containing mouthwashes in normal and dysplastic oral keratinocytes. J Oral Pathol Med. 2018 May;47(5):511-8. https://doi.org/10.1111/jop.12704
Sharma AP, Naqvi A, Sharma N, Haider K. Assessment of the association between oral health and hygiene practices and oral câncer: a hospital-based case-control study. Eur J Mol Clin Med. 2020;7(8):1206-11.
Saira, Ahmed R, Malik S, Khan MF, Khattak MR. Epidemiological and clinical correlates of oral squamous cell carcinoma in patients from north-west Pakistan. J Pak Med Assoc. 2019 Aug;69(8):1074-8.
Marques LA, Eluf-Neto J, Figueiredo RA, Góis-Filho JF, Kowalski LP, Carvalho MB, et al. Oral health, hygiene practices and oral cancer. Rev Saude Publica. 2008 Jun;42(3):471-9. https://doi.org/10.1590/S0034-89102008000300012
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021 Jun;134:178-89. https://doi.org/10.1016/j.jclinepi.2021.03.001
Brooke BS, Schwartz TA, Pawlik TM. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. 2021 Aug;156(8):787-8. https://doi.org/10.1001/jamasurg.2021.0522
World Health Organization. International classification of diseases for mortality and morbidity statistics (11th Rev). Geneva : World Health Organization; 2018.
Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma: an update. CA Cancer J Clin. 2015;65(5):401-21. https://doi.org/10.3322/caac.21293
GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. London: Cochrane; 2020.
Ryan R, Hill S. How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group. 2016;Version 3 :1-24. https://cccrg.cochrane.org/author-resources
Blot WJ, Winn DM, Fraumeni JF Jr. Oral cancer and mouthwash. J Natl Cancer Inst. 1983 Feb;70(2):251-3. https://doi.org/10.1093/jnci/70.2.251
Mashberg A, Barsa P, Grossman ML. A study of the relationship between mouthwash use and oral and pharyngeal cancer. J Am Dent Assoc. 1985 May;110(5):731-4. https://doi.org/10.14219/jada.archive.1985.0422
Young TB, Ford CN, Brandenburg JH. An epidemiologic study of oral cancer in a statewide network. Am J Otolaryngol. 1986;7(3):200-8. https://doi.org/10.1016/S0196-0709(86)80007-2
Winn DM, Blot WJ, McLaughlin JK, Austin DF, Greenberg RS, Preston-Martin S, et al. Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Res. 1991 Jun;51(11):3044-7.
D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May;356(19):1944-56. Available from: www.nejm.org https://doi.org/10.1056/NEJMoa065497
Assunção Junior N, Teixeira VP, Lemos CA. Use of mouthwashes in patients with oral and oropharyngeal cancer. Clinical and Laboratorial Research in Dentistry. 2015;21(2):91-8. https://doi.org/10.11606/issn.2357-8041.clrd.2015.102956
Talamini R, Vaccarella S, Barbone F, Tavani A, La Vecchia C, Herrero R, et al. Oral hygiene, dentition, sexual habits and risk of oral cancer. Br J Cancer. 2000 Nov;83(9):1238-42. https://doi.org/10.1054/bjoc.2000.1398
Chang JS, Lo HI, Wong TY, Huang CC, Lee WT, Tsai ST, et al. Investigating the association between oral hygiene and head and neck cancer. Oral Oncol. 2013 Oct;49(10):1010-7. https://doi.org/10.1016/j.oraloncology.2013.07.004
Alnuaimi AD, Wiesenfeld D, O’Brien-Simpson NM, Reynolds EC, McCullough MJ. Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study. Oral Oncol. 2015 Feb;51(2):139-45. https://doi.org/10.1016/j.oraloncology.2014.11.008
Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: etiology and risk factors: A review. J Cancer Res Ther. 2016;12(2):458-63. https://doi.org/10.4103/0973-1482.186696
Carlin V, Matsumoto MA, Saraiva PP, Artioli A, Oshima CT, Ribeiro DA. Cytogenetic damage induced by mouthrinses formulations in vivo and in vitro. Clin Oral Investig. 2012 Jun;16(3):813-20. https://doi.org/10.1007/s00784-011-0559-2
Zamora-Perez AL, Mariaud-Schmidt RP, Fuentes-Lerma MG, Guerrero-Velázquez C, Gómez-Meda BC, López-Verdín S, et al. Increased number of micronuclei and nuclear anomalies in buccal mucosa cells from people exposed to alcohol-containing mouthwash. Drug Chem Toxicol. 2013 Apr;36(2):255-60. https://doi.org/10.3109/01480545.2012.737804
Hernandes KC, da Silva CA, Schmidt VK, Boeira JM. Assessment of effects of mouthwash by buccal micronucleus cytome assay: a preliminary study. Rev Eletr Cient UERGS. 2016;2(3):267-75. https://doi.org/10.21674/2448-0479.23.267-275
Tomasetti C, Vogelstein B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015 Jan;347(6217):78-81. https://doi.org/10.1126/science.1260825
Schmidt J, Zyba V, Jung K, Rinke S, Haak R, Mausberg RF, et al. Effects of octenidine mouth rinse on apoptosis and necrosis of human fibroblasts and epithelial cells - an in vitro study. Drug Chem Toxicol. 2018 Apr;41(2):182-7.
https://doi.org/10.1080/01480545.2017.1337124
Balloni S, Locci P, Lumare A, Marinucci L. Cytotoxicity of three commercial mouthrinses on extracellular matrix metabolism and human gingival cell behaviour. Toxicol In Vitro. 2016 Aug;34:88-96. https://doi.org/10.1016/j.tiv.2016.03.015
Liu JX, Werner J, Kirsch T, Zuckerman JD, Virk MS. Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts. J Bone Jt Infect. 2018 Aug;3(4):165-72. https://doi.org/10.7150/jbji.26355
Khan S, Khan AU, Hasan S. Genotoxic assessment of chlorhexidine mouthwash on exfoliated buccal epithelial cells in chronic gingivitis patients. J Indian Soc Periodontol. 2016;20(6):584-91. https://doi.org/10.4103/jisp.jisp_9_17
U.S. Food and Drug Administration. 5 things to know about Triclosan. Published May 16, 2019 [cited 2022 Aug 16]. Available from: https://www.fda.gov/consumers/consumer-updates/5-thingsknow-about-triclosan
Zhang Y, Huang L, Wang D, Ren P, Hong Q, Kang D. The ROBINS-I and the NOS had similar reliability but differed in applicability: a random sampling observational studies of systematic reviews/meta-analysis. J Evid Based Med. 2021 May;14(2):112-22. https://doi.org/10.1111/jebm.12427
Hootman JM, Driban JB, Sitler MR, Harris KP, Cattano NM. Reliability and validity of three quality rating instruments for systematic reviews of observational studies. Res Synth Methods. 2011 Jun;2(2):110-8. https://doi.org/10.1002/jrsm.41
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Copyright (c) 2023 Jennifer Sanzya Silva de Araújo, Elma Izze da Silva Magalhães, Hassan Lavalier de Oliveira Lima, Maria Carmen Fontoura Nogueira da Cruz, Erika Barbara Abreu Fonseca Thomaz
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