Field cancerization in head and neck carcinoma - biomarkers and novel insights on surgical margins
09-10, 10:45–11:45 (Europe/Istanbul), Head & Neck Oncology 3

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<p>Description: The lack of suitable biomarkers for personalized treatment protocols and delineating field cancerization prevents further progress in clinical outcomes. In the light of this perspective, MicroRNAs could be promising biomarkers both in terms of diagnostic and prognostic value. The aim of this prospective study is to find strong prognostic microRNA biomarkers for advanced laryngeal carcinoma and molecular signatures of field cancerization. Sixty patients were enrolled and four samples were collected from each patient: tumor surface and depth, peritumor normal mucosa, and control distant laryngeal mucosa. Initially, a global microRNA profile was conducted in twelve patients from the whole cohort and subsequently, we validated a selected group of 12 microRNAs with RT-qPCR. The follow-up period was 24 months (SD ± 13 months). Microarray expression profile revealed 59 dysregulated microRNAs. The validated expression levels of miR-93-5p (χ2(2) = 4.68, log-rank p = 0.03), miR-144-3p (χ2(2) = 4.53, log-rank p =.03) and miR-210-3p (χ2(2) = 4.53, log-rank p = 0.03) in tumor samples exhibited strong association with recurrence-free survival as higher expression levels of these genes predict worse outcome. Tumor suppressor genes miR-144-3p (mean rank 1.58 vs 2.14 vs 2.29, p=0.000) and miR-145-5p (mean rank 1.57 vs 2.15 vs 2.28, p=0.000) were significantly dysregulated in peritumor mucosa with a pattern of expression consistent with paired tumor samples thus revealing a signature of field cancerization in laryngeal carcinoma. Additionally, miR-1260b, miR-21-3p, miR-31-3p and miR-31-5p were strongly associated with tumor grade. Our study reports the first global microRNA profile specifically in advanced laryngeal carcinoma that includes survival analysis and investigates the molecular signature of field cancerization. We report two strong biomarkers of field cancerization and three predictors for recurrence in advance stage laryngeal cancer.</p> <p>Published: https://www.nature.com/articles/s41598-022-20338-w</p> <p>Outcome Objectives: To demonstrate the possibilities of microRNA molecules as biomarkers and broaden the understanging of field cancerization among head and neck surgeons.</p> <p>1. Popov et al. Global microRNA expression profile in laryngeal carcinoma unveils new prognostic biomarkers and novel insights into field cancerization. Sci Rep. 2022 Oct 12;12(1):17051. doi: 10.1038/s41598-022-20338-w. [IF 4.9, Q1]</p> <p>1. Kyurkchiyan SG…Popov TM. Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue. Cells. 2024 Apr 5;13(7):633. doi: 10.3390/cells13070633. [IF 6.0, Q1]<br>2. Kyurkchiyan S, P….Popov TM. Co-expression of miRNA players in advanced laryngeal carcinoma - Insights into the roles of miR-93-5p, miR-145-5p, and miR-210-3p. Biomol Biomed. 2024 Sep 23. doi: 10.17305/bb.2024.10947. Epub ahead of print. PMID: 39412136. [IF 3.1, Q2]<br>3. Komitova K…; Popov, T.M. A Critical Review on microRNAs as Prognostic Biomarkers in Laryngeal Carcinoma. Int. J. Mol. Sci. 2024, 25, 13468. https://doi.org/10.3390/ijms252413468 [IF 4.9, Q1]<br>4. Popov TM, et al. Proangiogenic signature in advanced laryngeal carcinoma after microRNA expression profiling. Mol Biol Rep. 2020 Jul;47(7):5651-5655. doi: 10.1007/s11033-020-05250-8. Epub 2020 Jun 12. PMID: 32533400. [IF 2.6, Q2]</p>
<p>Despite recent advances in biological therapy, curative treatment options in head and neck cancer remain limited to surgery and/or chemoradiation therapy based on anatomic location and TNM staging. The lack of suitable biomarkers in this field ensue failure in defining subgroups eligible for more individualized treatment protocols, something that has already been established for many other solitary malignancies. Field cancerization is another major issue in head and neck cancer - the concept that most malignancies arise from contiguous monoclonal preneoplastic fields in the mucosa and a great number of the recurrences originate from remnants of these clonal fields.</p>
Moderator-Speaker Moderator-Speaker
Todor Popov
Speaker Speaker
Marco Ferrari
Linda Marklund
Mirza Markišić
Todor Popov
<p>Dr. Todor Popov is current Head of Department of ENT at the Medical University - Sofia, Bulgaria, a position he has held since May 2023. His surgical expertise encompasses a wide range of areas including head and neck surgery, microsurgical free flap reconstruction, transoral laser surgery, endoscopic sinus and skull base surgery, treatment of laryngeal stenosis, and various ear surgeries including cochlear implants. Dr. Popov's research focuses on genetics and epigenetics of head and neck carcinoma, neoangiogenesis, microRNAs, cancer field theory, and biomarkers. He has led several research projects and published numerous papers in reputable journals, demonstrating his significant contributions to the field. Fluent in English and German. Dr. Popov has participated in numerous fellowships and courses across Europe, continuously enhancing his skills in various aspects of ENT surgery. He has also been involved in multiple research projects, with a particular focus on microRNA expression in laryngeal carcinoma and its implications for prognosis and treatment. His work has been presented at major international congresses, including the European ORL-HNS Congress and the European Rhinologic Society Congress.</p>
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Marco Ferrari
<p>Marco Ferrari serves as Associate Professor at the University of Padova (Padova, Italy) and Consultant at the Padova University Hospital (“Azienda Ospedale Università Padova”; Padova, Italy). He trained in Brescia, Italy, and complete research fellowship in Toronto (Ontario, Canada) and Padova. His main interests are head and neck oncological surgery and ventral skull base surgery, with special interest for sinonasal, salivary, and mesenchymal cancers management. He authored a number of book chapters and peer-reviewed publications, and serves as reviewer and member of the editorial board for several journals. He also authored the book entitled Endoscopic Transnasal Anatomy of the Skull Base and Adjacent Areas, published by Thieme.</p>
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Linda Marklund
<p>Professor and Senior Consultant in Head and Neck Surgery, Otorhinolaryngology at Uppsala University Hospital and Karolinska University Hospital in Stockholm Sweden. Active research in Head and Neck cancer with special focus on HPV/p16, Sentinel Node, and brachyteraphy.</p>
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Mirza Markišić
<p>Dr. Mirza Markišić (born 1988 in Berane,Montenegro) is an Otorhinolaryngology specialist and Head&Neck oncology surgeon subspecialist at the Clinical Center of Montenegro. Graduated from the Faculty of Medicine in Podgorica in 2013, completing his residency in Podgorica and Belgrade. Co-authored a book on benign prostatic hyperplasia and attended prestigious Salzburg Weill Cornell seminars. Speaks English and French and has extensive experience in scientific research and medical projects.</p>
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