{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:01:32Z","timestamp":1784667692529,"version":"3.55.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009169","name":"Assiut University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009169","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Arch Otorhinolaryngol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Irregular vocal fold mucosal changes pose diagnostic challenges and may range from benign to malignant. Emerging research highlights Sex-determining Region Y-box 2 (SOX2) gene amplification as a potential early marker in head and neck tumorigenesis. This work aimed to evaluate vocal fold irregular mucosal lesions for the early detection of high-risk lesions (high-grade dysplasia, carcinoma in situ, and squamous cell carcinoma (SCC)) and to explored the potential role of SOX2 gene in early laryngeal carcinogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a prospective observational cross-sectional study with a follow-up up to 2 years; 40 male patients with vocal fold irregularities were examined by laryngo-stroboscopy, then classified into two groups based on histopathological diagnosis: (A) Low-risk group (benign lesions, low-grade dysplasia), (B) High-risk group (high-grade dysplasia, carcinoma insitu and SCC. Real-time polymerase chain reaction PCR was performed to detect SOX2 gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant differences were observed in vocal fold stroboscopic features (mucosal wave and amplitude), and SOX2 gene expression across lesion groups, with higher SOX2 expression noted in the high-risk group (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). A strong positive correlation was observed between histopathological severity and each of stroboscopic impairment in mucosal wave and amplitude, and Log SOX2 gene expression. The regression analysis showed a significant independent predictive effect of SOX2 gene expression on the progression to high-risk lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study integrated established diagnostic standards, laryngostroboscopy for clinical assessment, and histopathology as the gold standard for grading, while the analysis of SOX2 gene expression showed a promising predictive molecular marker for tumorigenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00405-026-10249-1","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:48:49Z","timestamp":1778532529000},"page":"4493-4504","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vocal folds irregular mucosal changes: a multimodal evaluation for diagnosis and genetic risk stratification"],"prefix":"10.1007","volume":"283","author":[{"given":"Essam Eldin Mohamed","family":"Aref","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira Hafez","family":"AbdelAal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-6851","authenticated-orcid":false,"given":"Rania Mohamed","family":"Ewida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1485-5227","authenticated-orcid":false,"given":"Reham Abdel Wakil","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"10249_CR1","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1007\/s12070-023-04183-5","volume":"76","author":"P Pavlidis","year":"2024","unstructured":"Pavlidis P, Tseriotis VS, Matthias C, Katsikari I, Chatzinikolaou A, Gouveris H (2024) Contact endoscopic surface vascular and epithelial morphology in leukoplakia and carcinoma of the vocal cords: Vascular and morphological changes of vocal folds in leukoplakia and cancer. Indian J Otolaryngol Head Neck Surg 76:462\u2013468. https:\/\/doi.org\/10.1007\/s12070-023-04183-5","journal-title":"Indian J Otolaryngol Head Neck Surg"},{"key":"10249_CR2","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1002\/hed.21862","volume":"34","author":"A Ferlito","year":"2012","unstructured":"Ferlito A, Devaney KO, Woolgar JA, Slootweg PJ, Paleri V, Takes RP, Strojan P, Bradley PJ, Rinaldo A (2012) Squamous epithelial changes of the larynx: Diagnosis and therapy. Head Neck 34:1810\u20131816. https:\/\/doi.org\/10.1002\/hed.21862","journal-title":"Head Neck"},{"key":"10249_CR3","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1007\/s00405-007-0549-9","volume":"265","author":"M Gugatschka","year":"2008","unstructured":"Gugatschka M, Kiesler K, Beham A, Rechenmacher J, Friedrich G (2008) Hyperplastic epithelial lesions of the vocal folds: Combined use of exfoliative cytology and laryngostroboscopy in differential diagnosis. Eur Arch Otorhinolaryngol 265:797\u2013801. https:\/\/doi.org\/10.1007\/s00405-007-0549-9","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"10249_CR4","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s00405-006-0078-y","volume":"263","author":"M Sadri","year":"2006","unstructured":"Sadri M, McMahon J, Parker A (2006) Management of laryngeal dysplasia: A review. Eur Arch Otorhinolaryngol 263:843\u2013852. https:\/\/doi.org\/10.1007\/s00405-006-0078-y","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"10249_CR5","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1080\/00016489.2017.1347826","volume":"137","author":"N Zhang","year":"2017","unstructured":"Zhang N, Cheng L, Chen M, Chen J, Yang Y, Xie M, Li C, Chen X-L, Zhou L, Wu H-T (2017) Relationship between laryngoscopic and pathological characteristics of vocal cords leukoplakia. Acta Otolaryngol 137:1199\u20131203. https:\/\/doi.org\/10.1080\/00016489.2017.1347826","journal-title":"Acta Otolaryngol"},{"key":"10249_CR6","doi-asserted-by":"publisher","unstructured":"Rzepakowska A, Sobol M, Sielska-Badurek E, Niemczyk K, Osuch-Wojcikiewicz E (2020) Morphology, vibratory function, and vascular pattern for predicting malignancy in vocal fold leukoplakia. J Voice 34:812 e819-812 e815. https:\/\/doi.org\/10.1016\/j.jvoice.2019.04.001","DOI":"10.1016\/j.jvoice.2019.04.001"},{"key":"10249_CR7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3390\/cancers11030286","volume":"11","author":"R Granda-D\u00edaz","year":"2019","unstructured":"Granda-D\u00edaz R, Men\u00e9ndez ST, Pedregal Mallo D, Hermida-Prado F, Rodr\u00edguez R, Su\u00e1rez-Fern\u00e1ndez L, Vallina A, S\u00e1nchez-Canteli M, Rodr\u00edguez A, Fern\u00e1ndez-Garc\u00eda MS (2019) The novel role of sox2 as an early predictor of cancer risk in patients with laryngeal precancerous lesions. Cancers 11:286. https:\/\/doi.org\/10.3390\/cancers11030286","journal-title":"Cancers"},{"key":"10249_CR8","doi-asserted-by":"publisher","first-page":"396","DOI":"10.3109\/00016489109137409","volume":"111","author":"MN Kotby","year":"1991","unstructured":"Kotby MN, Kirchner JA, Kahane JC, Basiouny SE, el-Samaa M (1991) Histo-anatomical structure of the human laryngeal ventricle. Acta Otolaryngol 111:396\u2013402. https:\/\/doi.org\/10.3109\/00016489109137409","journal-title":"Acta Otolaryngol"},{"key":"10249_CR9","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.otc.2019.03.014","volume":"52","author":"SA Ali","year":"2019","unstructured":"Ali SA, Smith JD, Hogikyan ND (2019) The white lesion, hyperkeratosis, and dysplasia. Otolaryngol Clin North Am 52:703\u2013712. https:\/\/doi.org\/10.1016\/j.otc.2019.03.014","journal-title":"Otolaryngol Clin North Am"},{"key":"10249_CR10","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1007\/s00405-015-3530-z","volume":"272","author":"A El-Demerdash","year":"2015","unstructured":"El-Demerdash A, Fawaz SA, Sabri SM, Sweed A, Rabie H (2015) Sensitivity and specificity of stroboscopy in preoperative differentiation of dysplasia from early invasive glottic carcinoma. Eur Arch Otorhinolaryngol 272:1189\u20131193. https:\/\/doi.org\/10.1007\/s00405-015-3530-z","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"10249_CR11","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1038\/s41598-018-20086-w","volume":"8","author":"JH Chung","year":"2018","unstructured":"Chung JH, Jung HR, Jung AR, Lee YC, Kong M, Lee JS, Eun YG (2018) Sox2 activation predicts prognosis in patients with head and neck squamous cell carcinoma. Sci Rep 8:1677. https:\/\/doi.org\/10.1038\/s41598-018-20086-w","journal-title":"Sci Rep"},{"key":"10249_CR12","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.bjorl.2018.04.014","volume":"85","author":"M Chen","year":"2019","unstructured":"Chen M, Li C, Yang Y, Cheng L, Wu H (2019) A morphological classification for vocal fold leukoplakia. Braz J Otorhinolaryngol 85:588\u2013596. https:\/\/doi.org\/10.1016\/j.bjorl.2018.04.014","journal-title":"Braz J Otorhinolaryngol"},{"key":"10249_CR13","doi-asserted-by":"publisher","first-page":"5789","DOI":"10.3390\/jcm11195789","volume":"11","author":"A Leduchowska","year":"2022","unstructured":"Leduchowska A, Morawska J, Pietruszewska W (2022) Videolaryngoendoscopic and stroboscopic evaluation in predicting the malignancy risk of vocal fold leukoplakia. J Clin Med 11:5789. https:\/\/doi.org\/10.3390\/jcm11195789","journal-title":"J Clin Med"},{"key":"10249_CR14","doi-asserted-by":"publisher","first-page":"e7033","DOI":"10.1097\/MD.0000000000007033","volume":"96","author":"W Cui","year":"2017","unstructured":"Cui W, Xu W, Yang Q, Hu R (2017) Clinicopathological parameters associated with histological background and recurrence after surgical intervention of vocal cord leukoplakia. Med (Baltim) 96:e7033. https:\/\/doi.org\/10.1097\/MD.0000000000007033","journal-title":"Med (Baltim)"},{"key":"10249_CR15","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3760\/cma.j.issn.1673-0860.2017.11.002","volume":"52","author":"J Li","year":"2017","unstructured":"Li J, Xu W, Cheng LY (2017) [application of stroboscopy and narrow band imaging endoscopy in the diagnosis of vocal cord leukoplakia]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 52:806\u2013811. https:\/\/doi.org\/10.3760\/cma.j.issn.1673-0860.2017.11.002","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"10249_CR16","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jvoice.2010.02.001","volume":"25","author":"CR Krausert","year":"2011","unstructured":"Krausert CR, Olszewski AE, Taylor LN, McMurray JS, Dailey SH, Jiang JJ (2011) Mucosal wave measurement and visualization techniques. J Voice 25:395\u2013405. https:\/\/doi.org\/10.1016\/j.jvoice.2010.02.001","journal-title":"J Voice"},{"key":"10249_CR17","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1177\/000348940111000401","volume":"110","author":"D Colden","year":"2001","unstructured":"Colden D, Zeitels SM, Hillman RE, Jarboe J, Bunting G, Spanou K (2001) Stroboscopic assessment of vocal fold keratosis and glottic cancer. Ann Otol Rhinol Laryngol 110:293\u2013298. https:\/\/doi.org\/10.1177\/000348940111000401","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"10249_CR18","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/cncr.30430","volume":"123","author":"EA Mroz","year":"2017","unstructured":"Mroz EA, Rocco JW (2017) The challenges of tumor genetic diversity. Cancer 123:917\u2013927. https:\/\/doi.org\/10.1002\/cncr.30430","journal-title":"Cancer"},{"key":"10249_CR19","doi-asserted-by":"publisher","first-page":"e95303","DOI":"10.1371\/journal.pone.0095303","volume":"9","author":"L Toschi","year":"2014","unstructured":"Toschi L, Finocchiaro G, Nguyen TT, Skokan MC, Giordano L, Gianoncelli L, Perrino M, Siracusano L, Di Tommaso L, Infante M (2014) Increased sox2 gene copy number is associated with fgfr1 and pik3ca gene gain in non-small cell lung cancer and predicts improved survival in early stage disease. PLoS ONE 9:e95303. https:\/\/doi.org\/10.1371\/journal.pone.0095303","journal-title":"PLoS ONE"},{"key":"10249_CR20","doi-asserted-by":"publisher","first-page":"113860","DOI":"10.1016\/j.biopha.2022.113860","volume":"156","author":"S Mirzaei","year":"2022","unstructured":"Mirzaei S, Paskeh MDA, Entezari M, Mirmazloomi SR, Hassanpoor A, Aboutalebi M, Rezaei S, Hejazi ES, Kakavand A, Heidari H, Salimimoghadam S, Taheriazam A, Hashemi M, Samarghandian S (2022) Sox2 function in cancers: Association with growth, invasion, stemness and therapy response. Biomed Pharmacother 156:113860. https:\/\/doi.org\/10.1016\/j.biopha.2022.113860","journal-title":"Biomed Pharmacother"},{"key":"10249_CR21","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41392-020-00242-3","volume":"5","author":"S Zhang","year":"2020","unstructured":"Zhang S, Xiong X, Sun Y (2020) Functional characterization of sox2 as an anticancer target. Signal Transduct Target therapy 5:135. https:\/\/doi.org\/10.1038\/s41392-020-00242-3","journal-title":"Signal Transduct Target therapy"},{"key":"10249_CR22","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861\u2013872. https:\/\/doi.org\/10.1016\/j.cell.2007.11.019","journal-title":"Cell"},{"key":"10249_CR23","doi-asserted-by":"publisher","first-page":"e8960","DOI":"10.1371\/journal.pone.0008960","volume":"5","author":"T Hussenet","year":"2010","unstructured":"Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembel\u00e9 D, Martinet N, Thibault C, Huelsken J, Brambilla E (2010) Sox2 is an oncogene activated by recurrent 3q26. 3 amplifications in human lung squamous cell carcinomas. PLoS ONE 5:e8960. https:\/\/doi.org\/10.1371\/journal.pone.0008960","journal-title":"PLoS ONE"},{"key":"10249_CR24","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.jcma.2016.03.010","volume":"79","author":"WS Song","year":"2016","unstructured":"Song WS, Yang YP, Huang CS, Lu KH, Liu WH, Wu WW, Lee YY, Lo WL, Lee SD, Chen YW, Huang PI, Chen MT (2016) Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in cd133-positive glioblastoma stem cells. J Chin Med Assoc 79:538\u2013545. https:\/\/doi.org\/10.1016\/j.jcma.2016.03.010","journal-title":"J Chin Med Assoc"},{"key":"10249_CR25","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1093\/carcin\/bgu094","volume":"35","author":"A Schrock","year":"2014","unstructured":"Schrock A, Bode M, Goke FJ, Bareiss PM, Schairer R, Wang H, Weichert W, Franzen A, Kirsten R, van Bremen T, Queisser A, Kristiansen G, Heasley L, Bootz F, Lengerke C, Perner S (2014) Expression and role of the embryonic protein sox2 in head and neck squamous cell carcinoma. Carcinogenesis 35:1636\u20131642. https:\/\/doi.org\/10.1093\/carcin\/bgu094","journal-title":"Carcinogenesis"},{"key":"10249_CR26","doi-asserted-by":"publisher","first-page":"e71140","DOI":"10.1371\/journal.pone.0071140","volume":"8","author":"Y Chen","year":"2013","unstructured":"Chen Y, Huang Y, Huang Y, Chen J, Wang S, Zhou J (2013) The prognostic value of sox2 expression in non-small cell lung cancer: A meta-analysis. PLoS ONE 8:e71140. https:\/\/doi.org\/10.1371\/journal.pone.0071140","journal-title":"PLoS ONE"},{"key":"10249_CR27","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/j.ejca.2013.01.005","volume":"49","author":"L Z\u00fcllig","year":"2013","unstructured":"Z\u00fcllig L, Roessle M, Weber C, Graf N, Haerle S, Jochum W, Stoeckli S, Moch H, Huber G (2013) High sex determining region y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity. Eur J Cancer 49:1915\u20131922. https:\/\/doi.org\/10.1016\/j.ejca.2013.01.005","journal-title":"Eur J Cancer"},{"key":"10249_CR28","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1016\/j.molonc.2015.05.006","volume":"9","author":"P Bayo","year":"2015","unstructured":"Bayo P, Jou A, Stenzinger A, Shao C, Gross M, Jensen A, Grabe N, Mende CH, Rados PV, Debus J (2015) Loss of sox2 expression induces cell motility via vimentin up-regulation and is an unfavorable risk factor for survival of head and neck squamous cell carcinoma. Mol Oncol 9:1704\u20131719. https:\/\/doi.org\/10.1016\/j.molonc.2015.05.006","journal-title":"Mol Oncol"}],"container-title":["European Archives of Oto-Rhino-Laryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-026-10249-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00405-026-10249-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-026-10249-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T20:06:21Z","timestamp":1784664381000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00405-026-10249-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10249"],"URL":"https:\/\/doi.org\/10.1007\/s00405-026-10249-1","relation":{},"ISSN":["0937-4477","1434-4726"],"issn-type":[{"value":"0937-4477","type":"print"},{"value":"1434-4726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"2 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Between March 2020 and August 2023, after approval from the Committee, Faculty of Medicine, Assiut University, Assiut, Egypt (IRB: 17200388), and registered on clinicaltrials.gov (ID: NCT 04006197), the ethical procedures were strictly enforced in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed written consent was obtained from the patient.","order":2,"name":"Ethics","label":"Consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None to be declared.","order":3,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}