{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:06:55Z","timestamp":1788941215717,"version":"build-2803163510"},"reference-count":8,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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; Neck"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lymphovascular invasion (LVI) is a recognized poor prognostic factor in head and neck squamous cell carcinoma (HNSCC), particularly for regional recurrence and overall survival. However, its role in predicting distant metastasis, especially in HPV\u2010negative HNSCC, remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association between LVI and distant metastasis in adult patients with operable HPV\u2010negative HNSCC who underwent primary surgical resection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted on 280 patients with HPV\u2010negative HNSCC treated with primary surgery at two academic institutions from 2017 to 2024. Demographic, clinical, pathological, treatment, and outcome data were extracted. Kaplan\u2013Meier analysis and multivariable Cox proportional hazards models were used to assess the association between LVI and distant metastasis\u2010free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 280 patients, 94 (33.6%) were LVI\u2010positive. Kaplan\u2013Meier analysis demonstrated worse distant metastasis\u2010free survival among patients with LVI\u2010positive tumors, with separation persisting at 2\u2009years (69.8% vs. 88.3%) and 3\u2009years (63.1% vs. 87.4%). In multivariable Cox regression adjusting for age, sex, T stage, N stage, PNI, ENE, and margin status, the association between LVI and distant metastasis was attenuated and was not statistically significant (HR 1.56, 95% CI 0.88\u20132.77,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.131). In a sensitivity model excluding N stage because of overlap with ENE, LVI remained associated with distant metastasis (HR 1.76, 95% CI 1.01\u20133.06,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.047).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LVI is associated with higher rates of distant metastasis and worse distant metastasis\u2010free survival in operable HPV\u2010negative HNSCC. However, this association is attenuated after adjustment for ENE and pN stage, suggesting that LVI may function as part of a broader adverse pathological phenotype rather than as an isolated independent predictor. These findings support the continued evaluation of LVI in postoperative risk stratification models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70469","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:33:07Z","timestamp":1788939187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Impact of Lymphovascular Invasion on Distant Metastasis in\n                    <scp>HPV<\/scp>\n                    \u2010Negative Head and Neck Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-7376","authenticated-orcid":false,"given":"Mark","family":"Khoury","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Mlynarek","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3218-2668","authenticated-orcid":false,"given":"Nader","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hier","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-5732","authenticated-orcid":false,"given":"Christina","family":"Tsien","sequence":"additional","affiliation":[{"name":"Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Shenouda","sequence":"additional","affiliation":[{"name":"Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Sultanem","sequence":"additional","affiliation":[{"name":"Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-876X","authenticated-orcid":false,"given":"Nathaniel","family":"Bouganim","sequence":"additional","affiliation":[{"name":"Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khashayar","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-2819","authenticated-orcid":false,"given":"Sabrina","family":"Wurzba","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8880-805X","authenticated-orcid":false,"given":"Marco","family":"Mascarella","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2010 Head and Neck Surgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010019\u20100602\u20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2021.03.007"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/00034894231211116"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201030939\u20108"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201099280\u20102"},{"key":"e_1_2_7_8_1","volume-title":"AJCC Cancer Staging Manual","author":"Amin M. 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