The molecular and clinical implications of human papillomavirus-16 mediated oropharyngeal squamous cell carcinoma

Schache, Andrew G ORCID: 0000-0001-9466-6038
The molecular and clinical implications of human papillomavirus-16 mediated oropharyngeal squamous cell carcinoma. Doctor of Philosophy thesis, University of Liverpool.

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The last three decades have seen a fundamental change in the profile of oropharyngeal squamous cell carcinoma (OPSCC) within the developed world. The incidence of OPSCC attributable to tobacco and alcohol exposure has been gradually declining whilst Human papillomavirus (HPV)-related OPSCC has seen a rapid increase. Detection of High Risk HPV has profound prognostic significance as it correlates with both a disease-specific and an overall survival advantage. The stringency of testing, both in terms of diagnostic and prognostic capacity is therefore of increasing importance. This study sought to define the relative abilities of the diagnostic tests presently available in clinical practice and to explore the potential of a novel test in reaching the improved stringency called for by the clinical community. Diagnostic biomarkers with prognostic capacity, such as those utilised in defining HPV status in this research have been well described, however, despite HPV positive OPSCC being biologically distinct from HPV negative malignancy, predictive biomarkers defining the transition from persistent to transforming infection are yet to be forthcoming. A lack of an apparent premalignant state, akin to that seen in HPV-mediated cervical malignancy has restricted biomarker recognition. This research aimed to better define the epigenetic state and clarify the impact of viral integration for the virus and host in HPV positive OPSCC. Although detectable epigenetic alterations, within the genome of the virus and that of the host, were capable of providing an improved description of this burgeoning disease state, they fell short of providing clinically relevant biomarkers. It was however demonstrated that the previously held concept of preferential E2 cleavage during viral integration as a means to disrupt gene expression, is overstated and the model persists to the exclusion of other viral and host genome disruptions. A paradigm shift may be necessary in HPV positive OPSCC to an understanding of obligatory viral integration, the significance of which however, is yet to be fully elucidated.

Item Type: Thesis (Doctor of Philosophy)
Additional Information: Date: 2013-08 (completed)
Subjects: ?? RC0254 ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 17 Feb 2014 16:25
Last Modified: 16 Dec 2022 04:39
DOI: 10.17638/00013433