Analysis of the oral microbiota in head and neck cancer and radiotherapy-induced side effects

Abstract

Head and neck squamous cell carcinoma is an aggressive cancer that requires radiotherapy as part of its treatment approach. Carcinogenesis is traditionally linked to tobacco use and the human papilloma virus, though recent evidence associates variations in the oral microbiota with this group of cancers. Oral microbes also influence how well radiotherapy is tolerated and post-radiotherapy oral health. This thesis examines the oral microbiota as a biomarker for head and neck cancer and seeks to determine the role played by the microbiota in the development of acute and chronic oral health side effects of radiotherapy. Comparison of genomic DNA extraction methods revealed the capability to simultaneously study the bacterial and fungal communities that exist in dental plaque and saliva, an approach vital to our understanding of the oral microbiota in head and neck cancer and its treatment. The optimal DNA extraction method was applied to saliva samples in order to evaluate microbial biomarkers of head and neck cancer. These data, along with inflammatory cytokine concentrations, revealed that the microbial and inflammatory profiles of head and neck cancer patients are more reflective of patients with compromised oral health than healthy controls. During radiotherapy, oral mucositis, an acute side effect characterised by ulceration and inflammation of the oral mucosa, was positively correlated with the abundance of anaerobic Gram-negative bacilli, including those implicated in periodontal disease. Post-radiotherapy, a four-week intervention with oral probiotic Streptococcus salivarius M18 had minimal impact on the composition and diversity of the oral microbiota and post-radiotherapy oral health. By applying molecular-based approaches to study the oral microbiota pre-, during and postradiotherapy, this research presents a theme that links periopathogenic oral microbes to negative clinical outcomes, thereby establishing the presence of a microbial-based risk factor for head and neck cancer and its treatment.