Elsevier

Vaccine

Volume 31, Issue 37, 20 August 2013, Pages 3863-3871
Vaccine

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: A transmission-dynamic modeling study

https://doi.org/10.1016/j.vaccine.2013.06.064Get rights and content

Highlights

  • Vaccinating girls against HPV is predicted to be highly cost-effective.

  • The most cost-effective vaccine will be determined by their relative prices.

  • At equal price, the quadrivalent is the most economically desirable HPV vaccine.

  • Results are sensitive to discounting, duration of protection and genital warts burden.

Abstract

Background

The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions.

Methods

We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs ($CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations.

Results

Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, $95/dose), using the quadrivalent and bivalent vaccines is estimated to cost $15,528 [12,056;19,140] and $20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is $32 [17;46] (using a $40,000/QALY-gained threshold). Results were most sensitive to discounting, time-horizon, differences in durations of protection and anogenital warts burden.

Conclusions

Vaccinating pre-adolescent girls against HPV is predicted to be highly cost-effective. If equally priced, the quadrivalent is the most economically desirable vaccine. However, ultimately, the most cost-effective HPV vaccine will be determined by their relative price.

Introduction

Over 40 human papillomavirus (HPV) genotypes are known to infect the anogenital tract [1]. Low oncogenic risk (LR) types, such as HPV-6/11, are responsible for anogenital warts (AGW) and recurrent respiratory papillomatosis (RRP) [2], [3]. Infection with high oncogenic risk (HR) types is a necessary cause of cervical cancer [4], and is associated with other anogenital (vulvar, vaginal, penile, and anal) [5], [6] and oropharyngeal cancers [7]. HR types HPV-16/18 and HPV-31/33/45/52/58 are detected in approximately 70% and 20% of cervical cancers [8], [9], respectively, and in 85–90% and <10% of other HPV-related non-cervical cancers [5], [6], [7].

Two HPV vaccines, which target HPV-6/11/16/18 (quadrivalent) and HPV-16/18 (bivalent) have shown 93–100% efficacy against vaccine-type persistent infection and cervical lesions [10], [11]. Given the availability of these vaccines in many countries, policymakers have to decide which one to use in their immunization programs. At a program-level, vaccine selection is complicated because the vaccines have different properties and have been made available at different prices. The quadrivalent vaccine can prevent HPV-6/11 AGW. On the other hand, a recent meta-analysis suggests that the bivalent vaccine confers greater cross-protection against HPV-31/33/45 than the quadrivalent, although this protection may wane with time [12]. A head-to-head immunogenicity trial has shown a significantly higher antibody response against HPV-16/18 for the bivalent vaccine than the quadrivalent, which may suggest longer duration of protection [13].

Cost-effectiveness is a key criterion for policy decisions [14]. Although there have been many cost-effectiveness analyses of girls-only HPV vaccination [15], [16], there is little evidence about the comparative cost-effectiveness of the quadrivalent and bivalent vaccines. The few modeling studies on this issue have conflicting results, and did not incorporate herd-immunity and/or the new evidence on type-specific cross-protection [17], [18], [19], [20], [21], [22]. The objectives of this study are to compare the cost-effectiveness of the quadrivalent and bivalent HPV vaccines within Canadian girls-only immunization programs including recent evidence on type-specific cross-protective efficacy and herd-immunity, and estimate the price difference in order for the vaccines to be equally cost-effective.

Section snippets

Model structure

We developed HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and disease [23], [24], [25]. In the model, individuals are attributed three different risk factors for HPV infection and/or disease: gender, sexual activity level and screening level. Eighteen HPV-types are modeled individually, including HPV-types 16/18/6/11/31/33/45/52/58. These types are assumed to be independent (no synergy or competition) with respect to transmission, persistence, and

Base case

Table 3 shows the population-level effectiveness and Fig. 1 shows the discounted QALYs-gained and cost offsets following girls-only HPV vaccination (see the online Appendix for dynamics over time). Under base-case assumptions (population = 10 million), vaccination with the quadrivalent and bivalent vaccines result in 22,766 [21,421;27,665] and 19,592 [17,712;24,227] discounted QALYs-saved over 70 years, respectively. This results in direct medical cost offsets of $178 million [128;205] for the

Discussion

Our modeling analysis suggests that vaccinating pre-adolescent girls against HPV is highly cost-effective irrespective of the vaccine used (<$25,000/QALY-gained), if the long-term benefits of preventing cancer are taken into account. At equal price, the quadrivalent is the most cost-effective vaccine, unless the duration of protection is considerably longer for the bivalent or AGW are excluded from the analysis. Hence, in most scenarios investigated, the bivalent vaccine needs to be cheaper

Acknowledgements

We are indebted to the Imperial College High Performance Computing Service (HPC), and Compute Canada for providing us with the power necessary to run the simulations. We would also like to thank Drs. Goggin, Sauvageau, Mayrand, Gilca, and Boulianne for comments on the model and analysis plan.

Contributors: MB designed the study, drafted the article, had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. MB,

References (83)

  • P. Beutels et al.

    Funding of drugs: do vaccines warrant a different approach

    Lancet Infect Dis

    (2008)
  • T.A. Westra et al.

    On discounting of health gains from human papillomavirus vaccination: effects of different approaches

    Value Health

    (2012)
  • B. Donovan et al.

    Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data

    Lancet Infect Dis

    (2011)
  • A.R. Giuliano et al.

    Epidemiology of human papillomavirus infection in men, cancers other than cervical and benign conditions

    Vaccine

    (2008)
  • S.P. Tully et al.

    Time for change? An economic evaluation of integrated cervical screening and HPV immunization programs in Canada

    Vaccine

    (2012)
  • S.M. Garland et al.

    Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine

    J Infect Dis

    (2009)
  • A.M. Pou et al.

    Adult respiratory papillomatosis: human papillomavirus type and viral coinfections as predictors of prognosis

    Ann Otol Rhinol Laryngol

    (1995)
  • D.M. Backes et al.

    Systematic review of human papillomavirus prevalence in invasive penile cancer

    Cancer Causes Control

    (2009)
  • H. De Vuyst et al.

    Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis

    Int J Cancer

    (2009)
  • A.R. Kreimer et al.

    Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review

    Cancer Epidemiol Biomarkers Prev

    (2005)
  • N. Munoz et al.

    Epidemiologic classification of human papillomavirus types associated with cervical cancer

    N Engl J Med

    (2003)
  • S.M. Garland et al.

    Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases

    N Engl J Med

    (2007)
  • M.H. Einstein et al.

    Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12–24 in a Phase III randomized study of healthy women aged 18–45 years

    Hum Vaccin

    (2011)
  • M. Brisson et al.

    Economic evaluation of human papillomavirus vaccination in developed countries

    Public Health Genomics

    (2009)
  • M. Jit et al.

    Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model

    BMJ

    (2011)
  • V.J. Lee et al.

    Cost-effectiveness of different human papillomavirus vaccines in Singapore

    BMC Public Health

    (2011)
  • A. Dee et al.

    A cost-utility analysis of adding a bivalent or quadrivalent HPV vaccine to the Irish cervical screening programme

    Eur J Public Health

    (2010)
  • M. Kohli et al.

    Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada

    BMC Public Health

    (2012)
  • T.A. Westra et al.

    Inclusion of the benefits of enhanced cross-protection against cervical cancer and prevention of genital warts in the cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands

    BMC Infect Dis

    (2013)
  • N. Van de Velde et al.

    Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis

    J Natl Cancer Inst

    (2012)
  • Brisson M, Van de Velde N, Drolet M, Boily MC, Franco EL, Mayrand MH, et al. HPV-advise: technical appendix to J Natl...
  • J.F. Laprise et al.

    Efficacité populationnelle et coût-efficacité des programmes de vaccination contre les VPH au Québec

    Report submitted to the Institut National de Santé Publique du Québec (INSPQ)

    (2012)
  • D.S. Shepard
  • R. Pitman et al.

    Dynamic transmission modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-5

    Med Decis Making

    (2012)
  • WHO

    Investing in health for economic development. Report of the commission on macroeconomics and health

    (2001)
  • WHO

    WHO-CHOICE: World Health Organization statistical information system: choosing interventions that are cost effective

    (2006)
  • Ministère de la Santé et des Services Sociaux du Québec (MSSS).

    Vigie – Interventions: Couverture vaccinale en milieu scolaire

    Flash Vigie

    (2010)
  • Statistics Canada Canadian Community Health Survey (CCHS – Cycle 3.1)

    (2005)
  • M. Drolet et al.

    The psychosocial impact of an abnormal cervical smear result

    Psychooncology

    (2012)
  • M. Drolet et al.

    The impact of anogenital warts on health-related quality of life: a 6-month prospective study

    Sex Transm Dis

    (2011)
  • A. Demers et al.

    Epidemiology of cervical abnormalities and utilization of related health care resources

    (2009)
  • Cited by (44)

    View all citing articles on Scopus
    View full text