Assessment of the population-level impact of a high coverage HPV immunisation programme in young females

Human papillomavirus (HPV) infection is common in England. Persistent HPV infection can cause cervical and other HPV-related cancers. In clinical trials, HPV vaccination was found to have very high efficacy against HPV infection and early HPV-related disease. The National HPV Immunisation Programme, using HPV16/18 vaccine, was introduced in the UK in September 2008 for females aged up to 18 years old. This thesis aims to evaluate the equity and coverage of HPV vaccination in England and the population-level impact of the vaccination programme on infection and early disease outcomes in young females. In this thesis, serological surveillance confirmed high coverage of HPV vaccination in the targeted female population. However, surveillance among women at higher risk of HPV infection indicated lower coverage among those born outside of the UK, from more deprived areas or with a previous diagnosis of chlamydia infection. The same higher-risk population was used to investigate a previous ecological observation of reduced genital warts diagnoses since the vaccination was introduced. I designed and conducted a case-control study to estimate the effectiveness of HPV16/18 vaccination against genital warts (which are largely caused by HPV6/11). This study found no evidence that HPV16/18 vaccination offered cross-protection against warts (adjusted odds ratio (95% CI):1.02 (0.72- 1.45)). My analyses of HPV infection surveillance data within the post-vaccination period (2010-2016) demonstrated substantial declines in prevalence of HPV16/18 infection in 16-18 year olds (8.2% in 2010/2011 compared to 1.6% in 2016) and of HPV31/33/45 (6.5% to 0.6%). This work provides evidence of substantial direct protection against HPV16/18 and some type-specific cross-protection. It also shows a strong herd protection effect of vaccination. Reassuringly, there was no evidence of other non-vaccine types becoming more common. The results of this thesis will inform future decisions about changes to the National HPV Immunisation Programme and the UK Cervical Screening Programme.