{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:53:07Z","timestamp":1781013187123,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Doctoral School of Semmelweis University, Surgical Medicine Division, through PhD scholarship funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: Extranodal extension (ENE) is a well-established adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated with reduced survival and the need for intensified therapy. Nutritional status\u2014commonly assessed using the Prognostic Nutritional Index (PNI) and Body Mass Index (BMI)\u2014also influences outcomes in HNSCC. However, whether or not ENE correlates with nutritional status has not been previously investigated. Methods: We conducted a retrospective cohort study of 109 treatment-na\u00efve HNSCC patients with pathologically confirmed nodal metastases who underwent primary tumor resection and neck dissection between 2014 and 2025 at a national tertiary center. ENE status was determined histologically. Nutritional status was evaluated using BMI, PNI, serum albumin, and percentage of weight loss at diagnosis. Statistical analyses included t-tests, Chi-square tests, ANOVA, Cox regression, Kaplan\u2013Meier survival analysis, and Full Factorial General Linear Models. Results: ENE was present in 54.1% of patients and significantly reduced overall survival (Kaplan\u2013Meier p = 0.006; Cox regression RR = 1.927, p = 0.008). No significant differences in BMI, PNI, weight loss, or serum albumin were observed between ENE-positive and ENE-negative groups. ENE prevalence varied significantly by tumor origin (p = 0.018), being highest in hypopharyngeal cancers (75.8%) and lowest in oral cavity tumors (25.0%). ENE status was independent of tobacco use, alcohol abuse, and all nutritional markers across TNM 8\/9 subgroups. Conclusions: ENE is a strong prognostic marker in HNSCC, appearing to be independent of nutritional status. The demonstrated heterogeneity of ENE prevalence among tumor subsites supports the need for individualized management approaches.<\/jats:p>","DOI":"10.3390\/nu18040706","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:05:11Z","timestamp":1771855511000},"page":"706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Between Nutritional Status and Extranodal Extension of Lymph Node Metastases in Head and Neck Squamous Cell Cancers"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-8266","authenticated-orcid":false,"given":"Korn\u00e9l","family":"D\u00e1nos","sequence":"first","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ty\u00e1s","family":"Majoros","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2508-6418","authenticated-orcid":false,"given":"Benedek","family":"Besenczi","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5427-5419","authenticated-orcid":false,"given":"Mohammad","family":"Aouf","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Otorhinolaryngology Department, Faculty of Medicine, Kafr El-Sheikh University, Kafr El-Sheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0023-1816","authenticated-orcid":false,"given":"Ang\u00e9la","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3723-9149","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Tam\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Department of Voice, Speech, and Swallowing Therapy, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4352-9066","authenticated-orcid":false,"given":"Imre","family":"Uri","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Henson, C.E., Abou-Foul, A.K., Morton, D.J., McDowell, L., Baliga, S., Bates, J., Lee, A., Bonomo, P., Szturz, P., and Nankivell, P. (2023). Diagnostic challenges and prognostic implications of extranodal extension in head and neck cancer: A state of the art review and gap analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1263347"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s12105-025-01753-7","article-title":"International Consensus Recommendations of Diagnostic Criteria and Terminologies for Extranodal Extension in Head and Neck Squamous Cell Carcinoma: An HN CLEAR Initiative (Update 1)","volume":"19","author":"Gupta","year":"2025","journal-title":"Head Neck Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156183","DOI":"10.1016\/j.prp.2025.156183","article-title":"Pathological extranodal extension in head and neck cancer: A prognostic biomarker with therapeutic ramifications and diagnostic pitfalls","volume":"274","author":"Chohan","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.ijrobp.2012.05.008","article-title":"Long-term follow-up of the RTOG 9501\/intergroup phase III trial: Postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck","volume":"84","author":"Cooper","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1056\/NEJMoa032641","article-title":"Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer","volume":"350","author":"Bernier","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/01635581.2022.2102659","article-title":"The Body Mass Index Paradox in Head and Neck Cancer: A Systematic Review and Meta-Analysis","volume":"75","author":"Hobday","year":"2022","journal-title":"Nutr. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.oraloncology.2018.05.027","article-title":"Impact of obesity on outcomes for patients with head and neck cancer","volume":"83","author":"Hicks","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-L\u00e1zaro, D., and Seco-Calvo, J. (2023). Nutrition, Nutritional Status and Functionality. Nutrients, 15.","DOI":"10.3390\/nu15081944"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e000425","DOI":"10.1136\/esmoopen-2018-000425","article-title":"Prognostic Nutritional Index as an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer","volume":"3","author":"Bruixola","year":"2018","journal-title":"ESMO Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.14639\/0392-100X-N2358","article-title":"The prognostic-nutritional index in HPV-negative head and neck squamous cell carcinoma treated with upfront surgery: A multi-institutional series","volume":"43","author":"Tomasoni","year":"2023","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.21037\/atm-21-4528","article-title":"Long-term and short-term prognostic value of the prognostic nutritional index in cancer: A narrative review","volume":"9","author":"Yan","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17117","DOI":"10.1038\/s41598-021-96598-9","article-title":"Pretreatment prognostic nutritional index as a prognostic marker in head and neck cancer: A systematic review and meta-analysis","volume":"11","author":"Luan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6599","DOI":"10.1007\/s00405-024-08865-w","article-title":"Prognostic nutritional index (PNI) correlates with survival in head and neck cancer patients more precisely than other nutritional markers\u2014Real world data","volume":"281","author":"Uri","year":"2024","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e18027","DOI":"10.1200\/JCO.2023.41.16_suppl.e18027","article-title":"Hypoalbuminemia, body mass index, and weight loss as predictors of outcomes in head and neck cancer","volume":"41","author":"Kennedy","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.clnu.2024.02.018","article-title":"The clinical significance of hypoalbuminaemia","volume":"43","author":"Allison","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s13193-018-0723-0","article-title":"Staging for Head and Neck Cancer: Purpose, Process and Progress","volume":"9","author":"Shah","year":"2018","journal-title":"Indian. J. Surg. Oncol."},{"key":"ref_17","first-page":"166","article-title":"Union for International Cancer Control 9(th) Edition TNM Classification for Head and Neck Malignancies: What is New?","volume":"63","author":"Bayram","year":"2025","journal-title":"Turk. Arch. Otorhinolaryngol."},{"key":"ref_18","unstructured":"(2025, January 02). 9th Edition of the UICC TNM Classification. Available online: https:\/\/www.uicc.org\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1001\/jamaoto.2025.0848","article-title":"A Proposal for HPV-Associated Oropharyngeal Carcinoma in the Ninth Edition Clinical TNM Classification","volume":"151","author":"Huang","year":"2025","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1200\/EDBK_320939","article-title":"Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer","volume":"41","author":"Huang","year":"2021","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1038\/s41379-022-01120-9","article-title":"Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis","volume":"35","author":"Xu","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ijom.2020.07.006","article-title":"Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases","volume":"50","author":"Mamic","year":"2021","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/cncr.11202","article-title":"Extent of extracapsular spread","volume":"97","author":"Greenberg","year":"2003","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S1368-8375(02)00052-0","article-title":"Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes","volume":"38","author":"Ferlito","year":"2002","journal-title":"Oral Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/hed.26499","article-title":"Lymph node characteristics and their prognostic significance in oral squamous cell carcinoma","volume":"43","author":"Arun","year":"2021","journal-title":"Head Neck"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.4236\/ijohns.2019.86023","article-title":"Head and Neck Cancer Early Identification of Malnutrition High Risk Patients and Quality of Life Optimization","volume":"8","author":"Silva","year":"2019","journal-title":"Int. J. Otolaryngol. Head Neck Surg."},{"key":"ref_27","first-page":"223","article-title":"Pretreatment nutritional risk as a prognostic factor in head and neck cancer patients receiving radiotherapy or chemoradiotherapy","volume":"28","author":"Liu","year":"2019","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Arora, A., Saini, S., and Gupta, M. (2022). Pattern of Nutritional Status in Node Negative Versus Node Positive Head and Neck Cancer Patients Undergoing Treatment\u2014A Prospective Cohort Study, Springer Science and Business Media LLC.","DOI":"10.21203\/rs.3.rs-1071915\/v1"},{"key":"ref_29","first-page":"XC6","article-title":"Correlation between Nutritional Status and Neutrophil\/Lymphocyte Ratio in Patients being Treated for Head and Neck Cancer. A Prospective Observational Study","volume":"17","author":"Arora","year":"2023","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Denaro, N., Bareggi, C., Galassi, B., Beltramini, G., Wekking, D., Proh, M., Ibba, T., Solinas, C., and Garrone, O. (2024). Nutrition in HNSCC: Is it a matter for oncologists? The role of multidisciplinary team-a narrative literature review. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1430845"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Belak, B., Palfi, E., Molnar, A., Blasszauer, C., Reibl, D., and L\u00f6vey, J. (2025). Long-term nutrition therapy leads to survival benefit in head and neck cancer patients receiving targeted or immunotherapy. A retrospective cohort study with real-world data. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1667150"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"de Bree, R., Meerkerk, C.D.A., Halmos, G.B., M\u00e4kitie, A.A., Homma, A., Rodrigo, J.P., L\u00f3pez, F., Takes, R.P., Vermorken, J.B., and Ferlito, A. (2022). Measurement of Sarcopenia in Head and Neck Cancer Patients and Its Association with Frailty. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.884988"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.nut.2009.08.026","article-title":"Study of lymphocyte subpopulations in bone marrow in a model of protein\u2013energy malnutrition","volume":"26","author":"Fock","year":"2010","journal-title":"Nutrition"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: Pathogenesis and Clinical Significance","volume":"43","author":"Soeters","year":"2019","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101520","DOI":"10.1016\/j.bjorl.2024.101520","article-title":"Risk factors for cervical lymph node metastasis in oropharyngeal cancer and its impact on prognosis","volume":"91","author":"Zhang","year":"2025","journal-title":"Braz. J. Otorhinolaryngol. (Engl. Ed.)"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sanabria, A., Shah, J.P., Medina, J.E., Olsen, K.D., Robbins, K.T., Silver, C.E., Rodrigo, J.P., Su\u00e1rez, C., Coca-Pelaz, A., and Shaha, A.R. (2020). Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review. Cancers, 12.","DOI":"10.3390\/cancers12041059"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, Y., Yu, X., Sun, Y., Miao, S., Liu, S., Li, Z., Yi, J., and An, C. (2021). Different Primary Sites of Hypopharyngeal Cancer Have Different Lymph Node Metastasis Patterns: A Retrospective Analysis from Multi-Center Data. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.727991"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/4\/706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:11:49Z","timestamp":1771855909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/4\/706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,22]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["nu18040706"],"URL":"https:\/\/doi.org\/10.3390\/nu18040706","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,22]]}}}