Characterising the microbiome and its diagnostic and prognostic value in head and neck cancer
Date
2024
Authors
Yeo, Kenny Ker Li
Editors
Advisors
Vreugde, Sarah
Fenix, Kevin
Fenix, Kevin
Journal Title
Journal ISSN
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Thesis
Citation
Statement of Responsibility
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Abstract
Head and Neck Cancers (HNCs) are often diagnosed at advanced stages, leading to poor survival rates. The asymptomatic nature of HNC progression makes early detection challenging, highlighting the urgent need for innovative diagnostics. Additionally, variability in treatment responses, including immunotherapies, suggests that a patient’s unique tumour microenvironment (TME) may influence therapeutic outcomes. Recent studies have uncovered significant roles of the microbiome in cancer, particularly the gut, oral, and tumour microbiomes, but their specific contributions to HNC as diagnostic and prognostic tools remain largely unexplored. This thesis focuses on studying the contributions of the oral and tumour microbiome in HNCs. Chapter 1 introduces the concept of the HNC microbiome and is an extensive literature review that covers key concepts on HNC pathology, treatment, microbiome identification strategies, and HNC microbiome studies related to diagnostics and prognostics. This chapter identified key issues that can impact how current studies in HNC microbiome are interpreted. This includes heterogeneity in study design, sample type, and sequencing technologies utilised. Although systematic reviews were conducted to mitigate inconsistent findings, this approach does not account for bioinformatics and sequencing differences. Chapters 2, 3 and 4 are results chapters written in manuscript form that aim to address these knowledge gaps. Chapter 2 is a provisionally accepted manuscript (under minor revisions) in Pathogens. It investigates the potential use of saliva or oral rinse as a diagnostic tool in HNC. Through a uniform bioinformatics re-analysis, this chapter re-evaluated whether these non-invasive sampling methods can reliably differentiate HNC patients from other individuals. The findings of this chapter underscore several limitations of short-read 16S rRNA sequencing as a diagnostic tool in HNC. Chapter 3 is a manuscript published in the Journal of Medical Microbiology. It is a systematic review and meta-analysis that investigated the tumour tissue HNC microbiome by comparing cancer, cancer-adjacent, and non-cancer samples from various cohorts. A consensus tissue microbiome was identified at the genus level to distinguish these tissue types. Importantly, these microbiome profiles were also associated with specific TME profiles and clinical outcomes. Chapter 4 is a manuscript published in the Archives of Microbiology. This study addresses the limitations of 16S rRNA short-read sequencing (SRS) by, for the first time, applying a longread sequencing (LRS) approach to profile the HNC tumour microbiome. Through direct comparisons of SRS and LRS-based 16S rRNA data from the same HNC tissue, this study highlights the strengths and weaknesses of each method and supports LRS as a technology offering species-level taxonomic resolution, critical for future HNC microbiome research. Chapter 5 concludes this thesis and discusses the future direction of this research. Collectively, the studies presented in this thesis offer novel insights into the using microbiomes as a prognostic and diagnostic tool in HNC, laying a strong foundation for future research into how these microbes can influence HNC pathophysiology.
School/Discipline
Adelaide Medical School
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2024
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