Elsevier

Vaccine

Volume 30, Issue 2, 5 January 2012, Pages 425-435
Vaccine

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

https://doi.org/10.1016/j.vaccine.2011.10.067Get rights and content

Abstract

Many jurisdictions have implemented universal human papillomavirus (HPV) immunization programs in preadolescent females. However, the cost-effectiveness of modified cervical screening guidelines and/or catch-up immunization in older females in Canada has not been evaluated. We conducted a cost-utility analysis of screening and immunization with the bivalent vaccine for the Canadian setting from the Ministry of Health perspective. We used a dynamic model to capture herd immunity and included cross-protection against strains not included in the vaccine. We found that adding catch-up immunization to the current program would be cost-effective, and that combining catch-up immunization with delaying the age at which screening is first initiated could result in cost savings and net health gains.

Highlights

► We conduct a cost utility analysis of HPV catch-up immunization and cervical screening strategies. ► The analysis uses a dynamic model that captures herd immunity and vaccine cross-protection. ► Adding catch-up immunization to an existing program in pre-adolescent females is cost-effective. ► Combining catch-up immunization with a delay in the age of initial screening is cost-saving.

Introduction

Cervical cancer continues to impose a considerable burden worldwide despite reduced incidence after the implementation of cervical cancer screening in the 1960s [1], [2]. In 2009 alone, an estimated 1300 women were diagnosed with cervical cancer and approximately 390 women died of this disease in Canada [3]. The estimated cervical cancer incidence in Canadian provinces ranges from 7 to 10 per 100,000 females per year, with the highest incidence occurring women aged 40–69 [4], [5].

The guidelines for cervical cancer screening in Canada state that all women aged 18 and over should be screened, initially with two smears one year apart. If these smears are within normal limits, then rescreening every three years is advised until the age of 69 [6]. The success of this program is reflected in the participation rate of women. The best national data currently available show 1-year participation rates do not vary greatly among provinces, ranging from 37% in British Columbia and Ontario to 44% in Nova Scotia with a 3-year participation rate of approximately 70% [7] across the country.

In the 1980s, infection by certain human papillomavirus (HPV) types was identified as a prerequisite for development of cervical cancer [8], [9]. High-risk HPV types 16 and 18 have been identified as being present in approximately 70% of cervical cancers [9]. Recently, two vaccines were developed that are effective in preventing HPV infection and development of pre-cancerous cervical lesions associated with types 16 and 18 [10], [11]. HPV vaccines are changing the landscape of cervical cancer prevention and treatment, with promise to reduce cervical cancer incidence still further.

Mathematical models can be used to project future costs and health outcomes of HPV immunization under various alternative immunization or screening strategies [4], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38]. These modeling studies have investigated topics such as [1] the cost-effectiveness of universal HPV immunization in pre-adolescent females compared to no immunization; [2] the effectiveness of different immunization strategies in reducing prevalence of lesions and cervical cancer over time; [3] the cost-effectiveness of vaccinating males; and [4] determining the number of women who need to be vaccinated to prevent one cervical cancer case or death.

However, the implementation of universal immunization programs for pre-adolescent females in many jurisdictions has generated new questions regarding screening and immunization strategies. For example, how effective and cost-effective, are catch-up immunization programs in older females who have not been vaccinated? Should screening recommendations change in response to the implementation of HPV immunization programs? What combined immunization/screening strategies are most effective for preventing cervical cancer and provide the best value for money? Moreover, emerging data from clinical trials may impact model predictions. For example, both bivalent and quadrivalent vaccines now report significant cross-protection against infection and high-grade lesions caused by high-risk HPV types not included in the vaccine, although differences between the two vaccines with respect to cross-protection and other parameters are also becoming more clear [10], [39], [40], [41], [42].

Our objective was to conduct an economic evaluation of [1] catch-up immunization programs in older females [2], starting cervical screening at a later age than in current practice, and [3] possible combinations of these two strategies, in a population where a universal HPV immunization program of pre-adolescent females is already in place. We conducted a cost-utility analysis based upon a dynamic (transmission) model. Cost utility analyses estimate the costs required per quality-adjusted-life-year gained by implementing an alternative strategy, relative to the current strategy. Transmission models are useful for capturing transmission mechanisms and hence herd immunity effects, which can alter cost-effectiveness estimates considerably [43], [44].

We parameterized the model with recently published data on properties of the bivalent vaccine, which is now licensed for use in Canada. Despite differences between the bivalent and quadrivalent vaccines in terms of strain composition, immunogenicity, cross-protection properties, and (possibly) efficacy in older women with previous exposure to HPV [10], [40], [41], [42], the bivalent vaccine has been evaluated less frequently than the quadrivalent vaccine, hence our economic evaluation will focus on the bivalent vaccine. Our model is tailored as closely as possible to Canada, where many provinces have implemented universal school-based programs and where a single payer (the Ministry of Health) is often responsible for supporting both immunization programs and cervical screening programs.

Section snippets

Model structure

An age-structured compartmental model of HPV transmission and immunization with the bivalent vaccine was developed. The population was stratified by age (15–19, 20–24, 25–34, 35–44, 45–54, 55–64, 65+), gender (male, female), disease status (for females: susceptible, infected, natural immunity, vaccine immunity, cervical intraepithelial (CIN) grade 1 lesion, CIN2/3 lesion, or squamous cell carcinoma (SCC); for males: susceptible, infected, or natural immunity); and HPV type (16/18, or other

Results

Our model predicts that a school-based program immunizing 80% of females at age 12 is cost-effective compared to no immunization (comparator 1; Table 5), yielding an incremental cost-utility ratio below a threshold of $50,000/QALY [88]. The baseline school-based program combined with school-based catch-up immunization is also cost-effective compared to no immunization at this threshold (comparator 2; Table 5). These results are robust under the probabilistic uncertainty analysis. The cost per

Discussion

Here we evaluated the effectiveness and cost-effectiveness of school-based and clinic-based catch-up HPV immunization and modified screening programs that start screening at an older age. We also evaluated the effectiveness and cost-effectiveness of school-based immunization at age 12 compared to no immunization, in order to compare our model to other published models that have assessed that comparator. Our dynamic model was largely parameterized from Canadian data sources and included herd

Conclusions

Catch-up HPV immunization of females, either through a school-based program or a clinic-based program, is predicted to be cost-effective in the Canadian setting: from the Ministry of Health perspective, it provides additional health benefits at a cost considered acceptable by commonly used cost-effectiveness standards. Moreover, combining catch-up immunization with a delay in the age of initial screening is predicted to be cost saving from the Ministry of Health perspective while also providing

Acknowledgements

CTB was supported by an operating grant from the Canadian Institutes of Health Research (CIHR), a CIHR New Investigator Award, and an Ontario Ministry of Research and Innovation Early Researcher Award with matching funds from GlaxoSmithKline Canada. APG was supported by the James S. McDonnell Foundation. The funders had no role in developing the research questions, conducting the research, or the decision to submit the paper. The authors are grateful to Chander Sehgal and four anonymous

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