{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:23:07Z","timestamp":1786123387544,"version":"build-2736575974"},"reference-count":84,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"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":["Head &amp;amp; Neck"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Detection of extranodal extension (ENE) can guide treatment planning for patients with oropharyngeal squamous cell carcinoma (OPSCC). This systematic review identifies molecular biomarkers predictive of ENE in both Human Papillomavirus (HPV)\u2010positive and HPV\u2010negative OPSCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review was conducted for relevant articles published between 1996 and July 2025. Studies were included if they included exclusively patients with OPSCC and evaluated the presence of ENE based on molecular biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten studies met inclusion criteria. Tumor tissue modified viral (TTMV)\u2010HPV DNA was not associated with ENE. Biomarkers associated with ENE included NOTCH\u20101 and WNT mutations and expression of podoplanin, Her3, and myoferlin. These biomarkers have also been linked with epithelial\u2010mesenchymal transition (EMT) in cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multiple genomic and molecular biomarkers have been identified in association with ENE in OPSCC, suggesting that ENE is characterized by an EMT phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70243","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:54:27Z","timestamp":1774576467000},"page":"2329-2340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarkers Associated With Extranodal Extension (\n                    <scp>ENE<\/scp>\n                    ) in Oropharyngeal Squamous Cell Carcinoma (\n                    <scp>OPSCC<\/scp>\n                    ): A Systematic Review"],"prefix":"10.1002","volume":"48","author":[{"given":"Lauren C.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naishaliz","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Universidad Central del Caribe School of Medicine  Bayamon Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-4237","authenticated-orcid":false,"given":"Alexander","family":"Ladenheim","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3109-7987","authenticated-orcid":false,"given":"Saral","family":"Mehra","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0771-4220","authenticated-orcid":false,"given":"Benjamin L.","family":"Judson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6341-9971","authenticated-orcid":false,"given":"Sara I.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avanti","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafar","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Clohessy","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansley M.","family":"Roche","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Otolaryngology, Head and Neck Surgery Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32832984c0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31841"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599814538605"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599820951176"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20279"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-024-16362-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.6009"},{"issue":"1","key":"e_1_2_8_9_1","first-page":"18","article-title":"Long\u2010Term Functional and Quality\u2010Of\u2010Life Outcomes After Transoral Robotic Surgery in Patients With Oropharyngeal Cancer","volume":"144","author":"Achim V.","year":"2018","journal-title":"JAMA Otolaryngology. 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