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]

Head and neck cancer is a common yet aggressive malignancy with a poor prognosis, particularly when diagnosed at advanced stages. Despite progress in surgical, chemotherapeutic, and radiotherapeutic interventions, overall disease control and patient survival rates remains low due to high rates of recurrence and therapeutic resistance. Head and neck cancer continues to be a challenging disease and many efforts across the world are in process to help diagnose, treat, manage and surveil this disease and the patients it affects. Treatment related toxicity are long lasting and affect patient quality of life and function. Advances in therapeutics and new technologies continue to be developed and utilized in management of this challenging disease. Neoadjuvant and adjuvant immunotherapy approaches are about to gain approval as standard of care. This may help select patients to de-intensify and if needed intensify surgical and non-surgical therapies. Continued advancement and study of therapeutic approaches are needed to increase response rates and maintain long term control in both HPV positive and negative cancers. Advances in diagnostics, treatment, surveillance and rehabilitation will continue to be needed to improve overall head and neck cancer patient outcomes.

This panel of experts will discuss new technologies, advances and treatment strategies in head & neck cancer. Speakers and panel discussion will focus on the future of innovation and unmet needs, as well as what is/are the next frontier(s) in head and neck cancer:

Faculty Roster for American Academy of Otolaryngology Panel Symposia:

Wojciech Mydlarz MD

Sidney Kimmel Comprehensive Cancer Center

Johns Hopkins University School of Medicine

Clint Allen MD

Center for Cancer Research/National Cancer Institute

National Institute of Health

Nicole Schmitt MD

Winship Cancer Institute

Emory University School of Medicine

Steven Chinn MD, MPH

Hillman Cancer Center

University of Pittsburgh Medical Center

Mark Zafereo MD University of Texas MD Anderson Cancer Center

Jaime Ku MD

Head and Neck Institute

Cleveland Clinic

Eleni Rettig MD

Brigham and Women's Hospital/Dana-Farber Cancer Institute

Harvard Medical School

Melina Windon MD

Markey Cancer Center

University of Kentucky School of Medicine

- Unmet needs in diagnosis, treatment, surveillance and rehabilitation of head and neck cancer

- Advances in treatment and response adjusted and directed therapy - Future of clinical trials in head and neck cancer; next frontier(s)?

- Artificial Intelligence in head and neck cancer