Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due to HPV types 16 and 18 using a transmission dynamic model
Introduction
It is now widely accepted that vaccination against the human papillomavirus (HPV) represents a new opportunity to reduce the incidence, and mortality associated with cervical cancer—an illness that kills more than 288,000 women each year worldwide [1]. Two vaccines have been developed to prevent HPV infections; a bivalent (Cervarix™) and a quadrivalent (Gardasil™). Both vaccines target HPV types 16 and 18. Gardasil™ is also directed against HPV types 6 and 11, which are related to anogenital lesions. Both vaccines have been shown to be effective in preventing cervical dysplasia in follow-up studies over a 5-year period of women that did not have HPV infection at the time of vaccination. Due to time constraints with the present study, only vaccination against HPV types 16 and 18 was considered.
Although the cost-effectiveness of both HPV vaccines are reported in the literature [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], results are variable; e.g., U.S. ($44,889/LYG and $32,066/LYG); France (€20,455/LYG); Canada ($31,000/QALY and $21,000/QALY for bivalent and quadrivalent, respectively); Australia ($51,103/LYG); Netherlands (€24,000/LYG); Mexico (US$ 2719/QALY); Brazil (I$120,820/YLS); Israel (US$ 81,404/QALY); Belgium (€68,078/LYG); Denmark (€11,441/LYG); Norway (€60,453/LYG); U.K. (£34,687/LYS). It is difficult therefore to generalize between results from various jurisdictions.
Variation in results generated from economic models is a common feature and may be explained by a number of factors including issues relating to model (structural) uncertainty and issues relating to parameter uncertainty. In the case of the HPV vaccine three types of HPV economic models have been reported in the literature: (1) cohort, (2) dynamic and (3) hybrid [15]. Cohort models are static models and are typically based on Markov models. Hybrid models are a combination of cohort and dynamic models. Hybrid and dynamic models are the only models, which take into account the transmission of infection in the population, i.e., susceptible persons have a lower risk of infection over time, even if they have not been vaccinated themselves, i.e., the herd immunity effect. However, dynamic models require more information, are more computationally intensive and can take a significant length of time to develop and yield results. Although associated with a greater level of uncertainty as compared with a cohort model, the results generated by a dynamic model can present a less biased estimate for the decision maker.
There are also many sources of parameter uncertainty. This uncertainty could in part be explained by some key input parameters, such as; the discount rate, potential vaccine coverage, vaccine efficacy, duration of protection of the vaccine, estimated cost of administration of the vaccine, direct medical costs, and assumptions related to HPV natural history, e.g., existence and duration of acquired immunity to HPV infection, age-dependency in infection, as well as disease progression/regression. An example is seen with the Danish HTA [12], which assumed lifelong protection from vaccination in the base-case analysis, whereas the Belgian and Norwegian HTAs assumed a booster dose would be required after 10 years [11], [13]. There were also differences in terms of the type of economic model used, cervical cancer screening programmes and clinical management of pre-malignant and invasive cervical cancer between countries. Some studies evaluated the cost-effectiveness of the vaccine against HPV types 16 and 18 only, whereas other studies also include the benefits of protection from HPV types 6 and 11 (associated with genital warts). Assessment of parameter uncertainty is also addressed in terms of the sensitivity analyses conducted. These analyses can vary from a simple univariate analysis to a more complex probabilistic multivariate analysis. The majority of evaluations published so far have reported univariate sensitivity analyses. Few evaluations published to date have conducted a probabilistic sensitivity analysis where the results are summarised in the form of a cost-effectiveness acceptability curve [5]. Cost-effectiveness acceptability curves show the probability that an intervention will be cost effective as the threshold cost-effectiveness ratio is varied.
The aim of the present study was to evaluate the cost-effectiveness of a combined primary (vaccination against HPV types 16 and 18) and secondary (population cervical cancer screening) approach to managing cervical intraepithelial neoplasia (CIN) 1–3 and invasive cervical cancer compared to a population cervical cancer screening programme alone in Ireland.
Section snippets
Framework
Prior to commencing the evaluation, the scope of the analysis was agreed with the economic modelling group in Denmark and an expert advisory group in Ireland. The base-case parameters for the model were established and the most appropriate data inputs were collected for the model.
Comparator
The study comparator was a population-based cervical cancer screening programme. A coverage rate of 80% was included as the base-case for the comparator (an internationally accepted target that national programmes
Model inputs
A list of model inputs are summarised in Table 3.
Cost-effectiveness of the base-case vaccination programme
In the base-case model, the total cost of the three-dose vaccine schedule (€100 per dose), including an administration fee of €30 per dose, would be approximately €9.73 million per year for a cohort of 12-year-old girls with a vaccine coverage of 80%. These costs will recur every year. The average savings from cases averted due to vaccination, over the 70 year time horizon, were estimated at €2.74 million per year (present day value). The average incremental cost per year per cohort of
Discussion
The aim of this economic evaluation was to assess the cost-effectiveness of HPV vaccination together with a cervical cancer screening programme as compared to a population cervical cancer screening programme alone, using an independent economic model. As such, infections caused by HPV types 6 and 11, as well as other cancers related to HPV, specifically cancers of the vulva and vagina in women, penile and anal cancers in men and mouth and oropharynx in both genders, were not considered in the
Conclusion
The results of this HTA suggest that vaccination against HPV types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer. The present study is a comprehensive and timely assessment of all of the current evidence on vaccination against HPV types 16 and 18, which can serve to inform health policy. As economic models incorporate a number of assumptions, the results are subject to a degree of uncertainty. HPV vaccines do not eliminate the need for cervical cancer
Acknowledgements
This paper formed part of an independent report commissioned and funded by the Health Information and Quality Authority (HIQA). The authors would like to thank the HTA Directorate and the Board of HIQA, as well as the members of the multidisciplinary Expert Advisory Group, which was established by HIQA to oversee the HTA process. The views expressed are not necessarily those of HIQA.
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