{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:15:54Z","timestamp":1793391354408,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Dental Research Foundation","award":["109-2021"],"award-info":[{"award-number":["109-2021"]}]},{"name":"Melbourne Dental School","award":["109-2021"],"award-info":[{"award-number":["109-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE\/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords \u201cbetel quid\u201d and \u201coral submucous fibrosis\u201d, and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers.<\/jats:p>","DOI":"10.3390\/biom12050664","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:08:58Z","timestamp":1651475338000},"page":"664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-1323","authenticated-orcid":false,"given":"Nicola","family":"Cirillo","sequence":"first","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Hung","family":"Duong","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wee Teng","family":"Er","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey Thao Nhi","family":"Do","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikkuwadura Eranda Harshan","family":"De Silva","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Dong","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sok Ching","family":"Cheong","sequence":"additional","affiliation":[{"name":"Translational Cancer Biology, Cancer Research Malaysia, 1 Jalan SS12\/1A, Subang Jaya 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-8981","authenticated-orcid":false,"given":"Elizabeth Fitriana","family":"Sari","sequence":"additional","affiliation":[{"name":"Dentistry and Oral Health, La Trobe Rural Health School, La Trobe University, Bendigo, VIC 3550, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7829-4684","authenticated-orcid":false,"given":"Michael J.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Melbourne Dental School, The University of Melbourne, Carlton, VIC 3053, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9794-2269","authenticated-orcid":false,"given":"Pangzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.","family":"Prime","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Regenerative Medicine, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,2]]},"reference":[{"key":"ref_1","first-page":"224","article-title":"Oral submucous fibrosis as a precancerous condition","volume":"92","author":"Pindborg","year":"1984","journal-title":"Scand J. 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