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