Vaccine 28 (2010) 4091–4102 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom Yoon Hong Choi a,b,* , Mark Jit a,e , Nigel Gay a , Andrew Cox a , Geoff P. Garnett c , William John Edmunds a,d a Modelling and Economics Unit, HPA Centre for Infections, 61 Colindale Avenue, Colindale, London, United Kingdom b Immunisation Department, HPA Centre for Infections, 61 Colindale Avenue, London, United Kingdom c Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom d Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom e Health Economics Unit, University of Birmingham, Birmingham, United Kingdom article info Article history: Received 16 July 2009 Received in revised form 22 September 2009 Accepted 30 September 2009 Available online 10 November 2009 Keywords: Human papillomavirus Mathematical modelling Vaccination abstract Many countries are considering vaccination against human papillomavirus (HPV). However, the long- term impact of vaccination is difficult to predict due to uncertainty about the prevalence of HPV infection, pattern of sexual partnerships, progression of cervical neoplasias, accuracy of screening as well as the duration of infectiousness and immunity. Dynamic models of human papillomavirus (HPV) transmission were developed to describe the infection spread and development of cervical neoplasia, cervical cancer (squamous cell and adenocarcinoma) and anogenital warts. Using different combinations of assumptions, 9900 scenarios were created. Each scenario was then fitted to epidemiological data and the best-fitting scenarios used to predict the impact of vaccination. Results suggest that vaccinating 12-year-old girls at 80% coverage will result in a 38–82% reduction in cervical cancer incidence and 44–100% reduction in anogenital warts incidence after 60 years of an ongoing vaccination programme if vaccine protection lasts 20 years on average. The marginal benefit of vaccinating boys depends on the degree of protection achieved by vaccinating girls. © 2009 Elsevier Ltd. All rights reserved. 1. Introduction Human papillomavirus (HPV) infection is necessary for the development of cervical cancer in women as well as anogenital warts in both men and women. Most diagnosed cervical cancers are squamous cell carcinomas; however, the incidence of adeno- carcinomas has been increasing rapidly [1] and now accounts for up to 20% of all cancer diagnoses in the United Kingdom (UK). Two HPV types (16 and 18) are responsible for about 70% of squamous cell carcinomas [2] and 85% of adenocarcinomas [3], while another two types (6 and 11) cause over 90% of cases of anogenital warts [4]. Two prophylactic vaccines against HPV have been developed: a bivalent vaccine (Cervarix TM ) against types 16 and 18, and a quadri- valent vaccine (Gardasil TM ) that also includes types 6 and 11. In clinical trials, use of either vaccine in HPV-naive females resulted in at least 90% reduction in persistent infection and associated dis- ease during 30 months of follow-up [5,6]. The quadrivalent vaccine * Corresponding author at: Immunisation Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, Colindale, London NW9 5EQ, United Kingdom. Tel.: +44 020 83277454; fax: +44 020 82007868. E-mail address: yoon.choi@hpa.org.uk (Y.H. Choi). has also been shown to be highly effective at preventing anogenital warts [7]. The vaccines have the potential to reduce the substantial burden of HPV-related disease. However, they are likely to be priced at lev- els significantly higher than other vaccines in national vaccination schedules, so their epidemiological and economic impact needs to be carefully considered. Because of the complexity of HPV infection and pathogenesis, as well as the long delays between infection and the most serious disease endpoints (cervical cancer), mathematical models are required to estimate the impact of vaccination. The majority of existing studies (reviewed in Ref. [8]) use static models, which explore the natural history of HPV infection on an individual level, but underestimate the population-wide impact of vaccination. Studies using dynamical models are rarer because of their greater demands in terms of both model complexity and data requirements in order to represent sexual contact patterns. However, they are required to take into account herd immunity and hence estimate the wider impact of vaccination. To date, one theoretical HPV transmission model has been published [9], and transmission models have been applied to assess HPV vaccination in the United States [10], Finland [11,12], Brazil [13] and the UK [14]. Most of these models assume a fixed structure to represent HPV transmission and progression between stages of disease. However, there are still significant gaps in our knowledge of 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.09.125