Molecular Targets in Head and Neck Cancer

Abstract

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.

Date of Award	2017
Original language	English
Awarding Institution	King's College London
Supervisor	Henrik Møller (Supervisor)