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Title: Molecular targets in head and neck cancer
Author: Qureishi, Ali Akhtar Siddique
ISNI:       0000 0004 6424 2359
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2017
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Background: Head and neck cancer (HNSCC) affects 650,000 people annually. Laryngeal cancer (LSCC) and oropharyngeal cancer (OPSCC) are amongst the commonest sub-types. For other cancers e.g. breast cancer, personalised treatments based on tumour markers have improved patient survival. With the exception of human papilloma virus (HPV); there are no clinically utilised biomarkers in HNSCC. Insulin growth factor receptor 1 (IGF-1R) and HPV are promising molecular markers in LSCC and OPSCC respectively. This thesis investigates the use of IGF-1R as a marker of radiotherapy resistance in LSCC and evaluates HPV detection in patients with OPSCC. Aims: • To assess IGF-1R as a marker of radiotherapy resistance in LSCC. • To determine the diagnostic accuracy of salivary PCR to detect HPV in patients with OPSCC. Methods: Immunohistochemistry (IHC) was used to compare IGF-1R levels between patients with LSCC achieving long-term remission and experiencing recurrence after radiotherapy. LSCC cells were used to create and interrogate an in vitro model of radiation resistance. Following the completion of a systematic review on HPV testing in OPSCC, a diagnostic accuracy study was performed to determine the sensitivity and specificity of saliva testing for HPV in OPSCC. Results: IGF-1R levels are higher in radioresistant LSCC and increase following radiotherapy. IGF-1R inhibition appears to be more effective at limiting cell survival in cells with IGF-1R overexpression. The sensitivity and specificity of saliva testing when compared to p16 IHC and HPV DNA in situ hybridisation is 72.2% and 90%. Conclusions: Elevated IGF-1R appears to associate with previous radiotherapy and radiotherapy resistance in LSCC. Treatments accounting for IGF-1R status, or molecular therapies targeting this receptor, may have merit in patients whose tumours overexpress IGF-1R. Saliva testing for HPV is a promising alternative to p16 IHC performed on tumour tissue. In selected patients, this might avoid the need for surgical biopsies and expedite treatment.
Supervisor: Moller, Henrik Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available