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.

Published: https://www.nature.com/articles/s41598-022-20338-w

Outcome Objectives: To demonstrate the possibilities of microRNA molecules as biomarkers and broaden the understanging of field cancerization among head and neck surgeons.

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]

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]

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]

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]

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]

Description: This proposal is focused on discussing the surgical feasibility of laryngeal preservation in advanced T3/T4 head and neck cancer, using the cricoarytenoid joint status as the primary assessment criterion. It is based on a a prospective, monocentric study conducted from 2020 to 2023, involving 162 patients with advanced T3/T4 squamous cell carcinoma of the head and neck. The study also assessed survival and dysphagia outcomes. Laryngeal preservation was feasible in 88% of cases when the cricoarytenoid joint was not invaded. No significant difference in recurrence-free survival was found between the laryngectomy and larynx preservation groups (78.9% vs. 85.1% recurrence-free rates). Transoral surgery resulted in faster recovery than open surgery (p = 0.001) and better overall survival (92.6% vs. 70.0%, p = 0.38). Long-term dysphagia levels and recurrence-free survival rates were similar between different surgical approaches.

Outcome Objectives: Define the theoretically possible limits for surgical preservation of the larynx and explore the possibilities of preservation surgery in advanced head and neck carcinoma beyond the theoretical red line of cricoarytenoid invasion in all directions.

1. Popov et al. Large monocentric prospective study on feasibility of functional preservation surgery of T3/T4 head and neck cancer - a pirouette around the cricoarytenoid joint. (under review)

2. Popov et al. Oncological outcomes of primary laryngectomy in T4 laryngopharyngeal cancer – study of 76 cases. Laryngorhinootologie 2019; 98(S 02): S80DOI: 10.1055/s-0039-1686049

3. Popov, T.M., Stancheva, G., Kyurkchiyan, S.G. et al. Global microRNA expression profile in laryngeal carcinoma unveils new prognostic biomarkers and novel insights into field cancerization. Sci Rep 12, 17051 (2022). https://www.nature.com/articles/s41598-022-20338-w

Hypopharyngeal carcinoma often presents at an advanced stage and requires aggressive multimodal treatment. Surgery plays a crucial role both as a primary option—combined with chemotherapy and radiotherapy—and increasingly as salvage therapy. Surgical procedures frequently involve neighboring organs such as the larynx and esophagus, making the reconstructive surgeon’s role particularly vital.This round table aims to provide a comprehensive overview of the reconstructive challenges related to hypopharyngeal defects, considering orientation, shape, extent (partial or circumferential), and involvement of adjacent structures.Topics include reconstruction with free and pedicled flaps, salvage settings, and laryngeal preservation. Special focus will be given to complications, pharyngoesophageal rehabilitation, and quality of life.