Human papillomavirus (HPV) associated oropharyngeal cancer : case prevalence, diagnosis, and the potential for screening in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Public Health at Massey University, Manawatu, New Zealand

Abstract

The incidence of oropharyngeal cancer (OPC) is increasing in developed countries, with many cases caused by Human Papilloma Virus (HPV). Since the mid-1990s, the incidence of OPC in New Zealand has almost quadrupled, but the role of HPV is uncertain. Thus, the objectives of this research were to establish the burden of HPV positive OPC in New Zealand, investigate diagnostic methods, early detection through PCR and cytology, and risk factors in a pre-vaccine population. The results presented in this thesis demonstrate an increased prevalence of HPV positive OPC from 61.9% in 1996-98 to 87.5% in 2010-12 in the study population. HPV 16 was responsible for 98.5% of HPV positive OPC and results from the multivariable model showed an HPV positive patient was more likely to be aged under 60 years old and diagnosed in 2010-12. Descriptive Analysis of questionnaire data from OPC patients found that having ever given oral sex was the most significant risk factor for having an HPV (p16) positive tumour. Comparison of p16, CK19, and HPV 16 DNA, RNA detection and viral load revealed ten cases in which the HPV status was incorrectly classified based on p16 alone, showing the need for clearer guidelines around the reporting of p16 results. These results are of particular importance as de-escalated therapies for HPV positive cases are under investigation. Moreover, viral nucleic acid and cytological abnormalities were detectable in brushings taken from conscious OPC patients. These previously undescribed cellular changes are comparable to cervical precancerous lesions and showed a continuum of dysplasia in p16 positive cases only. This warrants further investigation. Overall, this research has shown HPV positive OPC is a significant burden on the New Zealand health system and its incidence is increasing, thus supporting the recent inclusion of males into the nationally funded immunization schedule for Gardasil®9. However, OPC cases will continue to increase until the current vaccinated cohort reaches middle age. It is crucial that until this time, we focus on the early detection, improved diagnostics and reduced morbidities from treatment in the current prevaccine population.