{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:14:10Z","timestamp":1788401650878,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Perineural invasion (PNI) is an established adverse prognostic factor in oral squamous cell carcinoma (OSCC), but the implications of its extent as well as its relationship with surgical margin status and the extent of microscopic tumor spread remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 165 patients with OSCC treated surgically with curative intent between 2010 and 2019. PNI was assessed for presence, subtype, number of foci, location, and diameter of the largest involved nerve. Associations with margin status and survival outcomes were evaluated using univariate and multivariate analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PNI was present in 29 patients (17.6%) and was associated with advanced tumor stage, nodal metastasis, positive surgical margins (HR 3.4, 95% CI 1.1\u201310.2), and increased use of adjuvant radiotherapy. While PNI presence predicted poorer survival, the diameter of the largest invaded nerve provided superior prognostic discrimination. A cutoff of 200\u2009\u03bcm independently predicted disease\u2010specific survival (HR 5.7, 95% CI 1.7\u201319.0) and significantly improved multivariable model performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PNI correlates with positive surgical margins. Quantifying PNI, particularly nerve diameter, enhances prognostic stratification and may inform individualized surgical margin planning in OSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70461","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:32:36Z","timestamp":1788399156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Perineural Invasion Parameters for Risk Stratification in Oral Squamous Cell Carcinoma"],"prefix":"10.1002","author":[{"given":"Michael A.","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery University Hospital Zurich  Zurich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4078-0502","authenticated-orcid":false,"given":"Muriel D.","family":"Brada","sequence":"additional","affiliation":[{"name":"University of Zurich  Zurich Switzerland"},{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels J.","family":"Rupp","sequence":"additional","affiliation":[{"name":"University of Zurich  Zurich Switzerland"},{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosima E.","family":"Riemenschnitter","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery University Hospital Zurich  Zurich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-7270","authenticated-orcid":false,"given":"Simon","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery University Hospital Zurich  Zurich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-8483","authenticated-orcid":false,"given":"Alexander M.","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery University Hospital Zurich  Zurich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5261-6446","authenticated-orcid":false,"given":"Panagiotis","family":"Balermpas","sequence":"additional","affiliation":[{"name":"University of Zurich  Zurich Switzerland"},{"name":"Department of Radiation Oncology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6150-6772","authenticated-orcid":false,"given":"Gr\u00e9goire B.","family":"Morand","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery University Hospital Zurich  Zurich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"4","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.oraloncology.2008.05.017","article-title":"Current Concepts in Management of Oral Cancer\u2013Surgery","volume":"45","author":"Shah J. P.","year":"2009","journal-title":"Oral Oncology"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","DOI":"10.1177\/19160216251351562","article-title":"Oral Cavity Squamous Cell Carcinoma in Young Patients: A Multi\u2010Institutional Study of the Canadian Head & Neck Collaborative Research Initiative","volume":"54","author":"Hong X.","year":"2025","journal-title":"Journal of Otolaryngology \u2010 Head & Neck Surgery"},{"issue":"4","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/hed.25532","article-title":"Preoperative Assessment of CD44\u2010Mediated Depth of Invasion as Predictor of Occult Metastases in Early Oral Squamous Cell Carcinoma","volume":"41","author":"Morand G. B.","year":"2019","journal-title":"Head & Neck"},{"issue":"1","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-30111-7","article-title":"Maximum Standardized Uptake Value (SUV(Max)) of Primary Tumor Predicts Occult Neck Metastasis in Oral Cancer","volume":"8","author":"Morand G. B.","year":"2018","journal-title":"Scientific Reports"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2020.104938","article-title":"Optimum Surgical Margins in Squamous Cell Carcinoma of the Oral Tongue: Is the Current Definition Adequate?","volume":"111","author":"Singh A.","year":"2020","journal-title":"Oral Oncology"},{"issue":"5","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/hed.27339","article-title":"Stratification of Surgical Margin Distances by the Millimeter on Local Recurrence in Oral Cavity Cancer: A Systematic Review and Meta\u2010Analysis","volume":"45","author":"Young K.","year":"2023","journal-title":"Head & Neck"},{"issue":"1","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/lio2.4","article-title":"Perineural Invasion in Squamous Cell Carcinoma of the Oral Cavity: Histology, Tumor Stage, and Outcome","volume":"1","author":"Laske R. D.","year":"2016","journal-title":"Laryngoscope Investigative Otolaryngology"},{"issue":"5","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1001\/jamaoto.2024.5250","article-title":"Preoperative Clinical and Tumor Factors Associated With Adjuvant Therapy for Oral Cavity Cancer","volume":"151","author":"Dayan G. S.","year":"2025","journal-title":"JAMA Otolaryngology. Head & Neck Surgery"},{"issue":"2","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12105-018-0925-3","article-title":"Measuring Depth of Invasion in Early Squamous Cell Carcinoma of the Oral Tongue: Positive Deep Margin, Extratumoral Perineural Invasion, and Other Challenges","volume":"13","author":"Berdugo J.","year":"2019","journal-title":"Head and Neck Pathology"},{"issue":"1","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.31557\/apjcb.2026.11.1.251-257","article-title":"Decoding the UICC 9th Edition TNM Staging in Head and Neck Cancer: Key Updates for Clinical Practice","volume":"11","author":"Mondal J.","year":"2026","journal-title":"Asian Pacific Journal of Cancer Biology"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2020.01670","article-title":"Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype","volume":"10","author":"Morand G. B.","year":"2020","journal-title":"Frontiers in Oncology"},{"issue":"10","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.6004\/jnccn.2014.0142","article-title":"Head and Neck Cancers, Version 2.2014. Clinical Practice Guidelines in Oncology","volume":"12","author":"Pfister D. G.","year":"2014","journal-title":"Journal of the National Comprehensive Cancer Network"},{"issue":"1","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00405-022-07561-x","article-title":"Need for Adjuvant Radiotherapy in Oral Cancer: Depth of Invasion Rather Than Tumor Diameter","volume":"280","author":"Riemenschnitter C. E.","year":"2023","journal-title":"European Archives of Oto\u2010Rhino\u2010Laryngology"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejrad.2020.109480","article-title":"Measurement Variations of MRI and CT in the Assessment of Tumor Depth of Invasion in Oral Cancer: A Retrospective Study","volume":"135","author":"Waech T.","year":"2021","journal-title":"European Journal of Radiology"},{"issue":"2","key":"e_1_2_9_16_1","first-page":"122","article-title":"Head and Neck Cancers\u2010Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual","volume":"67","author":"Lydiatt W. M.","year":"2017","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"15","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1002\/cncr.24396","article-title":"Perineural Invasion in Cancer: A Review of the Literature","volume":"115","author":"Liebig C.","year":"2009","journal-title":"Cancer"},{"issue":"3","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/jso.23821","article-title":"Perineural Invasion in Oral Squamous Cell Carcinoma: Quantitative Subcategorisation of Perineural Invasion and Prognostication","volume":"111","author":"Aivazian K.","year":"2015","journal-title":"Journal of Surgical Oncology"},{"issue":"4","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/lary.31059","article-title":"Subcategorization of Perineural Invasion Stratifies Oral Cavity Squamous Cell Carcinoma Prognosis","volume":"134","author":"Fung N.","year":"2024","journal-title":"Laryngoscope"},{"issue":"16","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1158\/1078-0432.CCR-21-4543","article-title":"Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer","volume":"28","author":"Schmitd L. 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D.","year":"2013","journal-title":"JAMA Dermatology"},{"issue":"4","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1001\/jamadermatol.2015.4994","article-title":"Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease\u2010Specific Death: A Systematic Review and Meta\u2010Analysis","volume":"152","author":"Thompson A. K.","year":"2016","journal-title":"JAMA Dermatology"},{"issue":"6","key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/archotol.124.6.637","article-title":"Perineural Invasion in Squamous Cell Carcinoma of the Head and Neck","volume":"124","author":"Fagan J. J.","year":"1998","journal-title":"Archives of Otolaryngology \u2013 Head & Neck Surgery"},{"issue":"12","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1001\/jamadermatol.2023.3703","article-title":"Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis","volume":"159","author":"Massey P. R.","year":"2023","journal-title":"JAMA Dermatology"},{"issue":"2","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000542772","article-title":"Perineural Invasion for Risk Stratification in Cutaneous Squamous Cell Carcinoma: A Scoping Review","volume":"241","author":"Cr\u00fcts E. C.","year":"2025","journal-title":"Dermatology"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejcskn.2025.100743","article-title":"Evaluating Perineural Invasion Severity in Head and Neck Cutaneous Squamous Cell Carcinomas to Refine Prognostic Accuracy: A Retrospective Case\u2010Control Study","volume":"3","author":"Nozzoli F.","year":"2025","journal-title":"EJC Skin Cancer"},{"issue":"1","key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40463-021-00529-7","article-title":"Prognostic Factors of Head and Neck Cutaneous Squamous Cell Carcinoma: A Systematic Review","volume":"50","author":"Lubov J.","year":"2021","journal-title":"Journal of Otolaryngology \u2010 Head & Neck Surgery"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hed.70461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:32:40Z","timestamp":1788399160000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.70461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":30,"alternative-id":["10.1002\/hed.70461"],"URL":"https:\/\/doi.org\/10.1002\/hed.70461","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]},"assertion":[{"value":"2026-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hed.70461"}}