Project funded by the National Science Centre (NCN) under the OPUS 24 competition
Project number: 2022/47/B/NZ4/01719
Project value: 3,020,720.00 PLN
Funding amount for Łukasiewicz – PORT: 1,839,760.00 PLN
Project duration: 02/11/2023 – 01/11/2026
Project partner: Poznan University of Medical Sciences
Project manager: Associate Professor Patrycja Gazińska, PhD Eng.
Head and Neck Squamous Cell Carcinomas (HNSCC) constitute a diverse group of tumors that can develop in more than 30 regions of the head and neck, including the oral cavity, pharynx, and larynx. The major etiological factors contributing to HNSCC development are tobacco use and alcohol abuse, while the incidence is also increasing due to human papillomavirus (HPV) infection.
HNSCCs are anatomically classified based on the primary tumor site, which determines treatment strategies. When diagnosed early, the survival rate reaches 80–90%, but approximately 50% of patients with locally advanced disease experience recurrence, which remains the main cause of treatment failure. Despite improvements in therapies, prognosis for HNSCC patients remains poor, and current treatment options are associated with severe side effects. Surgical procedures and radiotherapy can impair breathing, swallowing, and speech, while radiotherapy may also cause radiation-induced fibrosis, damaging blood vessels that nourish muscles, nerves, and bones.
At present, no clinically applicable biomarkers exist to identify radioresistant tumors, and current patient stratification systems for radiotherapy response are insufficient, leading to suboptimal use of healthcare resources and delayed treatment adjustments.
Project objectives
The project aims to analyze digitized hematoxylin and eosin (H&E)-stained histopathological slides using digital pathology and artificial intelligence (AI) tools to investigate radioresistance mechanisms in HNSCC. Additionally, we plan to explore gene–protein relationships using advanced molecular pathology techniques, enabling the integration of genomic data with specific cellular populations within the tumor tissue.
Through these approaches, we aim to identify mechanisms of radioresistance while also elucidating the biological pathways responsible for radiation and chemotherapy sensitivity in certain HNSCC subtypes. Both digital and molecular pathology methodologies represent innovative and transformative tools in fundamental cancer biology research.
Scientific rationale
The pathomorphology of HNSCC plays a crucial role in developing resistance to radiotherapy. Premalignant lesions frequently extend to surgical margins, and even after tumor removal, they may serve as sources of local recurrence or new primary tumors. These changes occur within the extracellular matrix (ECM) — a structure providing both mechanical and biochemical support to surrounding cells.
Tumor cells coexist with various stromal and immune cell populations (e.g., fibroblasts, endothelial cells, and immune cells) that form part of the tumor microenvironment (TME) and modulate cancer progression by remodeling local conditions.
HNSCCs are characterized by significant molecular and phenotypic heterogeneity and harbor numerous genetic mutations.
Research hypothesis
We hypothesize that not only tumor cells but also minor alterations in the seemingly normal epithelium, as well as tumor-associated stromal and immune cells, play pivotal roles in regulating tumor function, disease progression, and response or resistance to radiotherapy.
A deeper understanding of the tumor microenvironment and its influence on tumor behavior will ultimately enhance our ability to explain and predict treatment sensitivity, resistance, and recurrence. Using computational and molecular pathology, we aim to identify histopathological features, reveal cell–cell interactions, and study biological processes within the tumor environment that are critical for tumor behavior and radioresistance.
