{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:33:17Z","timestamp":1784543597921,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adenoid cystic carcinoma (AdCC) is a rare, aggressive salivary gland malignancy with a poor prognosis due to metastasis and local recurrence. Although hypoxia\u2010inducible factors\u20101\/2\u03b1 (HIF\u20101\/2\u03b1) play crucial roles in AdCC, their pleiotropic effects remain poorly understood. This systematic review and meta\u2010analysis evaluates the impact of HIF\u20101\/2\u03b1 in AdCC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, and Web of Science to identify studies examining HIF\u20101\/2\u03b1 in AdCC. Study quality was assessed using the modified Newcastle\u2010Ottawa scale, and meta\u2010analyses were performed using IBM SPSS Statistics (Version 29).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen studies met inclusion criteria, with 10 studies encompassing 650 AdCC cases included in the meta\u2010analysis. Positive HIF\u20101\/2\u03b1 expression was reported in 77.4% of AdCC cases (95% CI: 0.630\u20130.919,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and was significantly correlated with tumor size (OR: 0.38, 95% CI: 0.16\u20130.89,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03), advanced stage (OR: 2.86, 95% CI: 1.74\u20134.71,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and distant metastasis (OR: 1.82, 95% CI: 1.02\u20133.25,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Human studies demonstrated significantly increased HIF\u20101\/2\u03b1 protein and mRNA expression in AdCC cases compared to control groups. Solid\u2010type AdCC exhibited predominantly higher nuclear HIF\u20101\u03b1 expression than cribriform and tubular subtypes. Additionally, in cell culture models, the hypoxia\u2010induced upregulation of these factors increased the expression of VEGF (20\u2010fold), BNIP3 (6\u2010fold), and NID1, promoting angiogenesis, epithelial\u2013mesenchymal transition, autophagy, and invasiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HIF\u20101\/2\u03b1 emerge as a pivotal drivers of AdCC progression, serving dual roles as prognostic biomarker and therapeutic target, necessitating further clinical investigation through multicenter validation studies.<\/jats:p>\n                  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