The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections.
References
[1]
Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, et al. (2010) Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ 341: c3493.
[2]
Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, et al. (2012) Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 13: 89–99.
[3]
Munoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, et al. (2010) Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst 102: 325–339.
[4]
Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, et al. (2012) Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 13: 100–110.
[5]
Wheeler CM, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, et al. (2009) The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16–26 years. J Infect Dis 199: 936–944.
[6]
Malagon T, Drolet M, Boily MC, Franco EL, Jit M, et al. (2012) Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12: 781–789.
[7]
Palmroth J, Merikukka M, Paavonen J, Apter D, Eriksson T, et al. (2012) Occurrence of vaccine and non-vaccine human papillomavirus types in adolescent Finnish females 4 years post-vaccination. Int J Cancer.
[8]
Hughes JP, Garnett GP, Koutsky L (2002) The theoretical population-level impact of a prophylactic human papilloma virus vaccine. Epidemiology 13: 631–639.
[9]
Barnabas RV, Laukkanen P, Koskela P, Kontula O, Lehtinen M, et al. (2006) Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses. PLoS Med 3: e138.
[10]
Baussano I, Ronco G, Segnan N, French K, Vineis P, et al. (2010) HPV-16 infection and cervical cancer: modeling the influence of duration of infection and precancerous lesions. Epidemics 2: 21–28.
[11]
Bogaards JA, Xiridou M, Coupe VM, Meijer CJ, Wallinga J, et al. (2010) Model-based estimation of viral transmissibility and infection-induced resistance from the age-dependent prevalence of infection for 14 high-risk types of human papillomavirus. Am J Epidemiol 171: 817–825.
[12]
Choi YH, Jit M, Gay N, Cox A, Garnett GP, et al. (2010) Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom. Vaccine 28: 4091–4102.
[13]
Elbasha EH, Dasbach EJ, Insinga RP (2008) A multi-type HPV transmission model. Bull Math Biol 70: 2126–2176.
[14]
Johnson HC, Elfstrom KM, Edmunds WJ (2012) Inference of Type-Specific HPV Transmissibility, Progression and Clearance Rates: A Mathematical Modelling Approach. PLoS One 7: e49614.
[15]
Van de Velde N, Brisson M, Boily MC (2010) Understanding differences in predictions of HPV vaccine effectiveness: A comparative model-based analysis. Vaccine 28: 5473–5484.
[16]
Leinonen M, Kotaniemi-Talonen L, Anttila A, Dyba T, Tarkkanen J, et al. (2008) Prevalence of oncogenic human papillomavirus infection in an organised screening population in Finland. Int J Cancer 123: 1344–1349.
[17]
Choi YH, Chapman R, Gay N, Jit M (2012) Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine types: quantification using a multi-type mathematical model. Vaccine 30: 3383–3388.
[18]
Coupe VM, Bogaards JA, Meijer CJ, Berkhof J (2012) Impact of vaccine protection against multiple HPV types on the cost-effectiveness of cervical screening. Vaccine 30: 1813–1822.
[19]
Bogaards JA, Coupe VM, Xiridou M, Meijer CJ, Wallinga J, et al. (2011) Long-term impact of human papillomavirus vaccination on infection rates, cervical abnormalities, and cancer incidence. Epidemiology 22: 505–515.
[20]
Van de Velde N, Boily MC, Drolet M, Franco EL, Mayrand MH, et al. (2012) Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. J Natl Cancer Inst 104: 1712–1723.
[21]
National Institute for Health and Welfare (THL) (2008–2009) School Health Promotion Study in Finland. Available: http://www.thl.fi/kouluterveyskysely/. Accessed 2013 Aug 8.
[22]
Kontula O, M？kinen M (2009) Between Sexual Desire and Reality: The Evolution of Sex in Finland. Family Federation of Finland.
[23]
Official Statistics of Finland, Changes in marital status: Newly married women by age and by age of spouse 2008. Available: http://tilastokeskus.fi/til/ssaaty/index？_en.html. Accessed 2013 Aug 8.
[24]
Giuliano AR, Lee JH, Fulp W, Villa LL, Lazcano E, et al. (2011) Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study. Lancet 377: 932–940.
[25]
Rodriguez AC, Schiffman M, Herrero R, Hildesheim A, Bratti C, et al. (2010) Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst 102: 315–324.
[26]
Trottier H, Ferreira S, Thomann P, Costa MC, Sobrinho JS, et al. (2010) Human papillomavirus infection and reinfection in adult women: the role of sexual activity and natural immunity. Cancer Res 70: 8569–8577.
[27]
Bulkmans NW, Berkhof J, Bulk S, Bleeker MC, van Kemenade FJ, et al. (2007) High-risk HPV type-specific clearance rates in cervical screening. Br J Cancer 96: 1419–1424.
[28]
Kretzschmar M (2000) Sexual network structure and sexually transmitted disease prevention: a modeling perspective. Sex Transm Dis 27: 627–635.
[29]
Laukkanen P, Koskela P, Pukkala E, Dillner J, Laara E, et al. (2003) Time trends in incidence and prevalence of human papillomavirus type 6, 11 and 16 infections in Finland. J Gen Virol 84: 2105–2109.
[30]
Bogaards JA, Kretzschmar M, Xiridou M, Meijer CJ, Berkhof J, et al. (2011) Sex-specific immunization for sexually transmitted infections such as human papillomavirus: insights from mathematical models. PLoS Med 8: e1001147.
[31]
Merikukka M, Kaasila M, Namujju PB, Palmroth J, Kirnbauer R, et al. (2011) Differences in incidence and co-occurrence of vaccine and nonvaccine human papillomavirus types in Finnish population before human papillomavirus mass vaccination suggest competitive advantage for HPV33. Int J Cancer 128: 1114–1119.
