Modelling the population-level impact of vaccination on the transmission of human papillomavirus type 16 in Australia
David G. Regan A D , David J. Philp B , Jane S. Hocking C and Matthew G. Law AA National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW 2052, Australia.
B The National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 0200, Australia.
C Key Centre for Women’s Health in Society, School of Population Health, University of Melbourne, Melbourne, Vic. 3010, Australia.
D Corresponding author. Email: d.regan@unsw.edu.au
Sexual Health 4(3) 147-163 https://doi.org/10.1071/SH07042
Submitted: 19 June 2007 Accepted: 22 June 2007 Published: 23 August 2007
Abstract
Background: Vaccines are now available to prevent the development of cervical cancer from genital human papillomavirus (HPV) infection. The decision to vaccinate depends on a vaccine’s cost-effectiveness. A rigorous cost-effectiveness model for vaccinated individuals is presented in a companion paper; this paper investigates the additional benefits the community might receive from herd immunity. Methods: A mathematical model was developed to estimate the impact of a prophylactic vaccine on transmission of HPV type 16 in Australia. The model was used to estimate the expected reduction in HPV incidence and prevalence as a result of vaccination, the time required to achieve these reductions, and the coverage required for elimination. The modelled population was stratified according to age, gender, level of sexual activity and HPV infection status using a differential equation formulation. Clinical trials show that the vaccine is highly effective at preventing persistent infection and pre-cancerous lesions. These trials do not, however, provide conclusive evidence that infection is prevented altogether. The possible modes of vaccine action were investigated to see how vaccination might change the conclusions. Results: The model predicts that vaccination of 80% of 12-year-old girls will eventually reduce HPV 16 prevalence by 60–100% in vaccinated and 7–31% in unvaccinated females. If 80% of boys are also vaccinated, reductions will be 74–100% in vaccinated and 86–96% in unvaccinated females. A campaign covering only 12-year-old girls would require 5–7 years to achieve 50% of the eventual reduction. With a catch-up campaign covering 13–26-year-olds, this delay would be reduced to only 2 years. Unrealistically high coverage in both sexes would be required to eliminate HPV 16 from the population. Under pessimistic assumptions about the duration of vaccine-conferred immunity, HPV 16 incidence is predicted to rise in some older age groups. Conclusions: Mass vaccination with a highly effective vaccine against HPV 16 has the potential to substantially reduce the incidence and prevalence of infection. Catch-up vaccination offers the potential to substantially reduce the delay before the benefits of vaccination are observed. A booster vaccination might be required to prevent an increase in incidence of infection in women over 25 years of age.
Additional keywords: cervical cancer, dynamic transmission model, herd immunity.
Acknowledgements
The authors wish to acknowledge Professor Niels Becker and Dr Kathryn Glass (The National Centre for Epidemiology and Population Health, The Australian National University) for advice on model construction and interpretation of results; Professor Anthony Smith (Australian Research Centre in Sex, Health and Society, La Trobe University) for providing data from the Australian Study of Health and Relationships; and Dr Lynne Conway and Dr Alicia Stein (CSL Limited), and Dr Shalini Kulasingam (Department of Obstetrics and Gynaecology, Duke University, North Carolina, USA) for advice on literature relating to vaccine trials and HPV natural history. The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, University of New South Wales. Dr David Regan is funded by a National Health and Medical Research Council Capacity Building Grant in Population Health. Dr David Philp is funded by an Australian Research Council Discovery Grant. Dr Jane Hocking is funded by a National Health and Medical Research Council Public Health Postdoctoral Research Fellowship.
[1] Xi LF, Koutsky LA. Epidemiology of genital human papillomavirus infections. Bull Inst Pasteur 1997; 95 161–78.
| Crossref | GoogleScholarGoogle Scholar |
[2] Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003; 16 1–17.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[3] Scheurer ME, Tortolero-Luna G, Adler-Storthz K. Human papillomavirus infection: biology, epidemiology, and prevention. Int J Gynecol Cancer 2005; 15 727–46.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[4] Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin Virol 2005; 32 16–24.
| Crossref | GoogleScholarGoogle Scholar |
[5] Doorbar J. The papillomavirus life cycle. J Clin Virol 2005; 32 7–15.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[6] Lowndes CM. Vaccines for cervical cancer. Epidemiol Infect 2006; 134 1–12.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[7] Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine 2006; 24 S4–S15.
| Crossref | GoogleScholarGoogle Scholar |
[8] Villa LL, Costa RLR, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005; 6 271–8.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[9] Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347 1645–51.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[10] Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia – a randomized controlled trial. Obstet Gynecol 2006; 107 18–27.
| PubMed |
[11] Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romonowski B, Roteli-Martins CM, et al. Sustained efficacy up to 4–5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367 1247–55.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[12] Villa LL, Ault KA, Giuliano AR, Costa RLR, Petta CA, Andrade RP, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 2006; 24 5571–83.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[13] Giannini SL, Hanon E, Moris P, Van Mechelen M, Morel S, Dessy F, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 2006; 24 5937–49.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[14] Villa LL, Costa RLR, Petta CA, Andrade RP, Paavonen J, Iversen OE, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006; 95 1459–66.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[15] Kulasingam S, Connelly L, Conway E, Hocking JS, Myers E, Regan D, et al. A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program. Sex Health 2007; 4 165–75.
| Crossref | GoogleScholarGoogle Scholar |
[16]
[17] Smith AMA, Rissel CE, Richters J, Grulich AE, de Visser RO. Australian study of health and relationships. Aust N Z J Public Health 2003; 27 103–256.
| PubMed |
[18] Ho GYF, Studentsov Y, Hall CB, Bierman R, Beardsley L, Lempa M, et al. Risk factors for subsequent cervicovaginal human papillomavirus (HPV) infection and the protective role of antibodies to HPV-16 virus-like particles. J Infect Dis 2002; 186 737–42.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[19] Luostarinen T, af Geijersstam V, Bjorge T, Eklund C, Hakama M, Hakulinen T, et al. No excess risk of cervical carcinoma among women seropositive for both HPV16 and HPV6/11. Int J Cancer 1999; 80 818–22.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[20] Rousseau MC, Villa LL, Costa MC, Abrahamowicz M, Rohan TE, Franco E. Occurrence of cervical infection with multiple human papillomavirus types is associated with age and cytologic abnormalities. Sex Transm Dis 2003; 30 581–7.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[21] Thomas KK, Hughes JP, Kuypers JM, Kiviat NB, Lee SK, Adam DE, et al. Concurrent and sequential acquisition of different genital human papillomavirus types. J Infect Dis 2000; 182 1097–102.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[22] Liaw KL, Hildesheim A, Burk RD, Gravitt P, Wacholder S, Manos MM, et al. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types. J Infect Dis 2001; 183 8–15.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[23] Ades AE, Nokes DJ. Modeling age-specific and time-specific incidence from seroprevalence – toxoplasmosis. Am J Epidemiol 1993; 137 1022–34.
| PubMed |
[24] Grenfell BT, Anderson RM. The estimation of age-related rates of infection from case notifications and serological data. J Hyg (Lond) 1985; 95 419–36.
| PubMed |
[25] Barnabas RV, Laukkanen P, Koskela P, Kontula O, Lehtinen M, Garnett GP. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses. PLoS Med 2006; 3 624–32.
| Crossref | GoogleScholarGoogle Scholar |
[26] Garnett GP, Anderson RM. Balancing sexual partnerships in an age and activity stratified model of HIV transmission in heterosexual populations. IMA J Math Appl Med Biol 1994; 11 161–92.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[27] Stanley M, Lowy DR, Frazer I. Prophylactic HPV vaccines: underlying mechanisms. Vaccine 2006; 24 S106–S13.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[28] Clifford GM, Gallus S, Herrero R, Munoz N, Snijders PJF, Vaccarella S, et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 2005; 366 991–8.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[29] Peto J, Gilham C, Deacon J, Taylor C, Evans C, Binns W, et al. Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort. Br J Cancer 2004; 91 942–53.
| PubMed |
[30] Burchell AN, Richardson H, Mahmud SM, Trottier H, Tellier PP, Hanley J, et al. Modeling the sexual transmissibility of human papillomavirus infection using stochastic computer simulation and empirical data from a cohort study of young women in Montreal, Canada. Am J Epidemiol 2006; 163 534–43.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[31] Moscicki AB, Schiffman M, Kjaer S, Villa LL. Updating the natural history of HPV and anogenital cancer. Vaccine 2006; 24 S42–S51.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[32] Giuliano AR, Harris R, Sedjo RL, Baldwin S, Roe D, Papenfuss MR, et al. Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the young women’s health study. J Infect Dis 2002; 186 462–9.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[33] Dasbach EJ, Elbasha EH, Insinga RP. Mathematical models for predicting the epidemiologic and economic impact of vaccination against human papillomavirus infection and disease. Epidemiol Rev 2006; 28 88–100.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[34] Elbasha EH, Dasbach EJ, Insinga RP. Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis 2007; 13 28–41.
| PubMed |
[35] Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC, et al. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis 2005; 191 1808–16.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[36] Franceschi S, Herrero R, Clifford GM, Snijders PJF, Arslan A, Anh PTH, et al. Variations in the age-specific curves of human papillomavirus prevalence in women worldwide. Int J Cancer 2006; 119 2677–84.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[37]
[38] Smith AMA, Rissel CE, Richters J, Grulich AE, de Visser RO. Sex in Australia: the rationale and methods of the Australian study of health and relationships. Aust NZ J Pub Health 2003; 27 106–17.
[39] Garnett GP, Anderson RM. Balancing sexual partnerships in an age and activity stratified model of HIV transmission in heterosexual populations. IMA J Math Appl Med Biol 1994; 11 161–92.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[40] Giuliano AR, Harris R, Sedjo RL, Baldwin S, Roe D, Papenfuss MR, et al. Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the young women’s health study. J Infect Dis 2002; 186 462–9.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[41] Peto J, Gilham C, Deacon J, Taylor C, Evans C, Binns W, et al. Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort. Br J Cancer 2004; 91 942–53.
| PubMed |
[42] Lowndes CM. Vaccines for cervical cancer. Epidemiol Infect 2006; 134 1–12.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
[43] Barnabas RV, Laukkanen P, Koskela P, Kontula O, Lehtinen M, Garnet GP. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses. PLoS Med 2006; 3 624–32.
| Crossref | GoogleScholarGoogle Scholar |
[44] Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2006; 107 18–27.
| PubMed |
[45] Kulasingam S, Connelly L, Conway E, Hocking JS, Myers E, Regan D, et al. A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program. Sex Health 2007; 4 165–75.
| Crossref | GoogleScholarGoogle Scholar |
