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Oral epithelial dysplasia (OED) can precede OSCC, offering a critical window for preventive and therapeutic intervention. This review maps the historical and current landscape of in\u00a0vitro and in\u00a0vivo models of OED, providing insight into their strengths, limitations, and translational relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and temporal analysis were conducted following PRISMA guidelines, with literature searches performed across Medline, EMBASE, EBM Reviews, and Web of Science.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 4009 records, 292 studies from 26 countries were included, yielding 307 models of OED. Only a minority of studies (17.4%) focused primarily on dysplasia as a precancerous condition. In\u00a0vivo models predominated (88.9%), while in\u00a0vitro systems were comparatively scarce and largely limited to 2D cultures. Organoid\u2010based approaches were rarely reported, highlighting a gap in advanced model development. Reproducibility data were available for 125 studies (45.8%). The hamster emerged as the most frequently used animal [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200996, 35%], and 4\u2010nitroquinoline\u20101\u2010oxide (4\u2010NQO) remained the most common carcinogen, particularly in murine models. A strong sex bias was observed, with male animals heavily over\u2010represented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, models of OED remain under\u2010represented and under\u2010developed, particularly in comparison to innovations in other fields of cancer research. Despite the central role of OED in oral carcinogenesis, current models do not adequately reflect clinical diversity or exploit modern 3D and patient\u2010derived technologies. This review provides a critical reference point to guide future studies toward more accurate, reproducible, and clinically relevant models, with the potential to advance prevention, early detection, and targeted therapies for OSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70149","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T10:22:20Z","timestamp":1778667740000},"page":"755-773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Models of Oral Epithelial Dysplasia: A Systematic Review and Temporal Analysis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4437-0605","authenticated-orcid":false,"given":"Zilefac Brian","family":"Ngokwe","sequence":"first","affiliation":[{"name":"Melbourne Dental School The University of Melbourne  Carlton Victoria 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