{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:21:08Z","timestamp":1780600868773,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recep Tayyip Erdogan University Development Foundation","award":["02024011025176"],"award-info":[{"award-number":["02024011025176"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Tumor budding (TB)\u2014clusters of one to five tumor cells at the invasive front\u2014has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin\u2013eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (\u22644 buds) and high-risk (&gt;4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan\u2013Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18\u2013108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76\u20130.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3\u20139.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6\u201335.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2\u201320.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation.<\/jats:p>","DOI":"10.3390\/jcm14155224","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T16:04:51Z","timestamp":1753286691000},"page":"5224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Tumor Budding in Head and Neck Cancers on Neck Lymph Node Metastasis and Prognosis"],"prefix":"10.3390","volume":"14","author":[{"given":"O\u011fuz","family":"G\u00fcl","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem \u00c7elebi","family":"Erdivanl\u0131","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-7454","authenticated-orcid":false,"given":"Mehmet","family":"Birinci","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suat","family":"Terzi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metin","family":"\u00c7eliker","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7481-4718","authenticated-orcid":false,"given":"O\u011fuzhan","family":"Ok\u00e7u","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-214X","authenticated-orcid":false,"given":"\u00c7i\u011fdem","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011fba","family":"Yemi\u015f","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Beyazal","family":"\u00c7eliker","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zerrin","family":"\u00d6zergin Co\u015fkun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2070-8677","authenticated-orcid":false,"given":"Engin","family":"Dursun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Lokman Hekim University, Ankara 06510, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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