{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:56:16Z","timestamp":1791244576252,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"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":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study is to analyze the impact of extranodal extension (ENE) on survival outcomes for patients with metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The pooled hazard ratios (HRs) and the 95% confidence interval (CI) were calculated to define the impact of ENE on overall survival (OS) and disease\u2010free survival (DFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 2076 patients (males: 84.4%) with a median age of 73.3\u2009years were included. The incidence of ENE was 65.6% (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091299\/1979). The median follow\u2010up time was 38.4\u2009months (95% CI: 21\u201338.4). The estimated pooled HRs were 1.31 (95% CI: 0.72\u20132.39;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.28) and 1.80 (95% CI: 0.53\u20136.10;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.22) for OS and DFS, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ENE may not be a reliable prognostic factor in metastatic cHNSCC. Further prospective studies are needed to refine risk stratification and improve the current nodal classification system.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.28251","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T12:19:44Z","timestamp":1752495584000},"page":"3275-3284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Extranodal Extension in Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-7785","authenticated-orcid":false,"given":"Andrea","family":"Costantino","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery  Celebration Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-4028","authenticated-orcid":false,"given":"Gian Marco","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Zimello","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-0727","authenticated-orcid":false,"given":"Elena","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Otorhinolaryngology Unit, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of \u2018Organi di Senso\u2019 University \u201cSapienza\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Polimeni","sequence":"additional","affiliation":[{"name":"Department of Odontostomatological and Maxillofacial Sciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-3589","authenticated-orcid":false,"given":"J. Scott","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery  Celebration Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0738-8223","authenticated-orcid":false,"given":"Armando","family":"De Virgilio","sequence":"additional","affiliation":[{"name":"Department of \u2018Organi di Senso\u2019 University \u201cSapienza\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000173202.56739.9f"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21898"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.02.046"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12553"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20417"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15324"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33373"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2018.4515"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2024.3103"},{"key":"e_1_2_8_11_1","unstructured":"National Comprehensive Cancer Network Head and Neck Cancers (version 4.2024)(2024) https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/head\u2010and\u2010neck.pdf."},{"key":"e_1_2_8_12_1","unstructured":"National Comprehensive Cancer Network Squamous Cell Skin Cancers (version 1.2025)(2025) https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/squamous.pdf."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20279"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.0941"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_8_16_1","volume-title":"Methods for the Development of NICE Public Health Guidance","author":"National Institute for Health and Care Excellence","year":"2012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8013"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1164"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5453"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467\u20109868.2010.00749.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1009"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn204"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1221"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24692"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21574"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0145561316095010-1106"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/ans.16413"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21965"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405\u2010021\u201006944\u2010w"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ans.13757"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23684"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2018.3650"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20608"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.TPS9597"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS9592"},{"key":"e_1_2_8_37_1","volume-title":"Adjuvant Libtayo (cemiplimab) Significantly Improves Disease\u2010Free Survival (DFS) After Surgery in High\u2010Risk Cutaneous Squamous Cell Carcinoma (CSCC) in Phase 3 Trial","year":"2025"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33773"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27121"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010011\u20101986\u20107"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01752"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.24883"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2020.104855"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26410"}],"container-title":["Head &amp; 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