Current trends suggest that the prevalence of oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) is increasing. Although Indigenous Australians have high rates of OPSCC, the incidence of oral HPV and the associated risk factors in this group are unknown. This thesis is an embedded component of a larger National Health and Medical Research Council (NHRMC) funded project titled 'Human Papillomavirus and Oropharyngeal Carcinoma amongst Indigenous Australians'. This thesis primarily explores the prevalence of HPV infections, accompanied by a qualitative insight regarding awareness and prevention strategies amongst Indigenous populations. The thesis is broadly divided into seven sections, with each section comprising twelve Chapters. Section A is an introduction of the thesis and includes Chapter 1, which is an overview of HPV, oropharyngeal carcinoma, and cancer burden amongst Indigenous Australians. Chapter 2 includes a review of the literature summarizing the prevalence of oral HPV amongst Indigenous populations globally and the prevalence of high-risk HPV infections amongst Indigenous populations. The Chapter concludes by highlighting identified gaps in research, followed by the aim and a basic outline of this thesis. Section B comprises Chapter 3, which describes the objectives of the larger HPV project and outlines the nested aims and expected contributions covered in this thesis. It describes the methodology and study design highlighting the research questions explored. Section C includes Chapter 4, which comprises comparative research highlighting the general health and oral health inequalities faced by Indigenous Australians. It includes analyses of the data collected as a part of the broader HPV project. Section D comprises three Chapters (Chapters 5 to 7), which provide details of HPV infection more broadly among Indigenous Australians. Chapter 5 is a systematic review and meta- analysis on the prevalence of HPV infection amongst Indigenous Australians. Chapter 6 is an analysis of the risk factors associated with incidence, persistence, and clearance of oral HPV infection at 12 months, as observed in the HPV project. Baseline findings of the HPV project showed an unexpectedly high prevalence of HPV 13 and 32, which are frequently associated with Heck's Disease (asymptomatic, benign neoplastic condition caused by HPV 13 or 32). Chapter 7 is a critical review of literature for Heck's disease and provides an insight into the age, sex, clinical presentation, genetic predisposition, ethnic association, global burden, and available treatment strategies. Section E is the qualitative component of this thesis, and includes Chapters 8 and 9. Chapter 8 addresses the high risk of Indigenous populations at a global level in experience of both HPV infection and HPV-related cancers. It presents a social-ecological model of HPV infection awareness and cervical cancer prevention among Indigenous women, offering a holistic and practical approach for Indigenous health policymakers. Chapter 9 is the psychological evaluation of the different emotions felt by Indigenous participants after hearing about cancer in the family or community. It discusses the critical importance of psycho-oncology, and the considerations for Indigenous peoples. Section F includes Chapter 10, involving the discussion of future objectives arising from this research. Clinical examinations are to be included in the next phase of this project and this Chapter is a proposition of using confocal imaging as a suitable screening tool and its diagnostic test of accuracy. This thesis identifies the general and oral health inequalities faced by Indigenous Australians, and the increased burden of HPV infection and its associated carcinomas. An ethnic predisposition to Heck's disease was identified with a large proportion of affected people having an Indigenous origin. The qualitative component identified a large gap regarding the awareness and prevention of HPV infection amongst Indigenous populations. It also produces a model to address this gap at an individual, family, community, and system level. The psycho- oncological evaluation demonstrated that, for Indigenous peoples, the experience of cancer care is complex as the health of an individual is determined by the emotional, cultural, social, and physical well-being of an entire community. The diagnostic test of accuracy for confocal laser endomicroscopy shows exceptionally high sensitivity and specificity for diagnosing oral squamous cell carcinoma. The next step would be its transference to a clinical setting and its adaptation as a portable tool for screening of oropharyngeal cancer amongst Indigenous Australians.Thesis (Ph.D.) -- University of Adelaide, Adelaide Dental School, 202
