Oropharyngeal cancers are increasing in incidence worldwide, and many of these tumours are caused by the human papillomavirus. This is a DNA virus that integrates into the host's genetic information, and can cause cancer through suppression of important tumour suppressors such as p53. TP53 is a gene that codes for p53, and in many cancers of the head and neck this is thought to be mutated. In NI, limited emigration provides an excellent context for research that depends on long-term follow up of patients. This study assesses molecular and demographic characteristics of patients and their tumours, in order to build a comprehensive of the emerging disease of oropharyngeal cancer. Methods Retrospective review of head and neck pathology reports was conducted for a twelve-year period, and all primary oropharyngeal squamous cell carcinomas were included. Detailed clinical and pathological information was gathered about patients and their tumours, and tissue microarrays were created for analysis of protein markers. In addition, DNA and RNA were extracted from a cohort of tumours, to study the tumour suppressor p53, and its family member p63. Different HPV testing methods were compared with one another, in order to ascertain the most reliable test for diagnosing presence of active virus in the oropharynx. Outcomes It was determined that testing for HPV is necessary in tumours arising in the oropharynx, and the best testing method for this appears to be detection of HPV DNA using chromatin in situ hybridisation. p53 mutations were found at a rate comparable with other studies in the head and neck, however the mutation profile appeared to be slightly different to that of other anatomical subsites. Studies of TP63 gene expression revealed that high levels of delta-Np63 are associated with disease recurrence and decreased survival, suggesting a role for this in tumour invasion and metastasis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:678211 |
| Date | January 2015 |
| Creators | Moran, Michael |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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