Elsevier

Vaccine

Volume 25, Issues 37–38, 17 September 2007, Pages 6677-6691
Vaccine

Cost–utility analysis of vaccination against HPV in Israel

https://doi.org/10.1016/j.vaccine.2007.07.018Get rights and content

Abstract

Using WHO-CHOICE methodology, we calculated cost–utility ratios for various interventions (PAP smear, HPV-DNA testing, VIA and vaccination against HPV) at various frequencies to reduce the burden of cervical cancer and condyloma (in the case of the HPV vaccination) in Israel, which has a low prevalence of cervical cancer. Assuming non-waning efficacy, HPV vaccinations will become cost-effective, very cost-effective and cost saving when the cost per dose falls below $96.85, $50.42 and $27.20, respectively. Attempts should be made to raise compliancy with PAP smears from the current opportunistic 12.2–20.0% per annum either before and/or after the vaccination is introduced.

Introduction

Worldwide, cervical cancer is the second most common cancer in females, with around half a million new cases occurring annually. In 2002, Cervical cancer caused 7.6% (239,000 deaths) of all female deaths due to malignant neoplasm worldwide [1], around 2% of total weighted years of life lost in women aged 25–64 [2] and around 9.4% of the burden of disease in females attributable to malignant neoplasm [1].

The burden of disease from cervical cancer is inversely related to the level of economic development. Mortality rates range from 113 per million population in Sub-Saharan Africa down to 19 per million in the most developed countries [1]. Data from the Israeli cancer registry show Israel to have a relatively low incidence of cervical cancer of 28 per million population (based on 184 new cases occurring annually during the 2000–2005 period) compared with 82 per million worldwide. Israel's low incidence rate can be partly explained by a large abstinence from pre-marital sexual relations in all the religious (Jewish, Moslem and Christian) sectors of society, the practice of male circumcision among Jews and Moslems [3] and possibly the religious prohibition by the family purity laws of orthodox Jews from having sexual intercourse both during menses and 6–7 days after its complete cessation, although the latter risk factor can be confounded by the near absence of other risk factors such as early coitarche, multiple partners and smoking [4].

Israel's mortality rate of 11 per million population (71 deaths in 2004) is considerably lower than rates in other developed countries (averaging 19 per million). This results in Israel's disability adjusted life year (DALY) loss of 193 per million population [5] from cervical cancer being about two-thirds that of the 261 DALY per million rate of the world's developed countries and around 13% that of the 1505 DALY per million burden in Sub-Saharan Africa.

Prevention by using cervical smears to detect pre-invasive and early disease has been shown to lead to significant reductions in both incidence and mortality in many countries [6], [7]. In June 2006, the USA FDA approved [8] the introduction of a safe, well-tolerated [9], [10] and immunogenic vaccine, which has proved effective [11], [12], [13], [14], [15], [16], [17], [18] against the cancer-causing human papillomaviruses (HPV) [19], [20], [21], [22]. The availability of the vaccine against HPV has increased considerably the number of available strategies in the fight against cervical cancer, making the right choices as to how to reduce cervical cancer has therefore become more complex than ever before.

Cost-effectiveness or cost–utility analyses combining the disciplines of epidemiology and economics, will not only help guide decision-makers to choose the optimal allocation of resources amongst the various cervical cancer interventions, but also between cervical cancer interventions and interventions for other conditions and diseases [23], [24].

The purpose of this study, utilizing standard methods and companion tools [25], [26], [27], [28], [29], [30], [31], is to compare and evaluate the costs and effectiveness of different screening and preventive strategies relating to cervical cancer in Israel.

This cost–utility analysis will hopefully help answer important policy questions such as whether and what type and frequency of screening programme for cervical cancer should be adopted in Israel, where 100% of the population has access to treatment. Specific emphasis will be given to evaluating the marginal costs and gains of the new vaccination against HPV.

Section snippets

The WHO-CHOICE framework

Generalized cost-effectiveness analysis (GCEA) is characterized by the assessment of costs and effects against the “null scenario”, which represents the theoretical absence of interventions for a particular condition. WHO-CHOICE (CHOosing Interventions that are Cost Effective) [8], [17] comprises of sector and population-level cost-effectiveness analyses (CEA) based on the GCEA framework. This approach facilitates and enhances [32] the ability to compare CEA findings across a wide range of

Unit costs

The unit costs (Table 1a) of the interventions consisted of the component costs of facilities, human resources, disposable medical devices, reusable medical devices (including transportation costs) and pharmaceutical costs (including transportation and cold-chain costs). Unit costs per screening test ranged from around $8 for VIA to $16 for PAP, $32 for HPV-DNA and $40 for combined PAP-HPV-DNA testing. Vaccine costs were based on the current price of $120 per dose, resulting in a cost of around

Sensitivity analysis

Clearly the cost utility of all interventions containing vaccinations is very sensitive to the unit vaccine cost (Table 3), whose future trends are unpredictable downwards. A further unknown is the true long-term efficacy of the vaccine. For our scenario of vaccinating 6 times a lifetime, we assumed that the vaccines 94.3% efficacy against the 16/18 genotypes would start to wane at an absolute rate of 2.5% per annum after 10 years. Altering this waning rate did not significantly change the cost

Discussion

HPV vaccinations represent a major potential public health achievement, joining Hepatitis B vaccinations as the only vaccinations against cancer.

Cost-effectiveness models based mainly on developed countries have reported a wide range of incremental costs per life year for some of the cervical cancer screening interventions, examined in this article, over and above that of treatment alone. Major contributory factors to such wide ranges besides differences in incidence rates, are the

Acknowledgements

The authors wish to thank the following for contributing data and/or knowledge to the study: Taghreed Adam (WHO/EIP), Martin L. Brown (NIH, Bethesda MD), Dan Chisholm (WHO/EIP), Sue Goldie (Harvard School of Public Health), Peter Heinmann (Essential Health Technologies Medical Research Council, Cape Town). Ben Johns (WHO/EIP), Jane Kim (Harvard School of Public Health), Jeremy Lauer (WHO/EIP), Cedric Mahe (IARC, Lyon), Julia Partnick (NHS Screening Programme, Sheffield), Cecilia Sepulveda (WHO)

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