A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

Cervical cancer caused by infection with carcinogenic types of human papillomavirus (HPV) is the second most common cancer in women worldwide according to age-standardized incidence rates (ASR). In 2008, there were more than a half million new cases and 274,000 deaths due to cervical cancer [1]. More than 85% of these cases occurred in low- and middle-income countries (LMICs), with the highest incidence rates in Sub-Saharan Africa, South-Central Asia, Latin America and Melanesia [2]. The United Republic of Tanzania has one of the highest cervical cancer burdens in the world and the highest in Eastern Africa, with an ASR of 50.9 cases per 100,000 women.

The World Health Organization (WHO) recommends routine vaccination of 9- to 13-year-old girls to protect against HPV infections with types 16 and 18, which contribute to the development of approximately 70% of cervical cancers [3] in countries where: (1) the prevention of cervical cancer and/or other HPV-related diseases is a public health priority; (2) vaccine introduction is programmatically feasible; (3) sustainable financing can be secured; and (4) the cost-effectiveness of vaccination strategies in the country or region has been duly considered [3]. In most LMICs, the vaccine price offered to the public sector (ranging from US$15 to more than US$130 per dose) has been a barrier for vaccine uptake. The GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization) is opening a finance window to purchase HPV vaccine at or about US$5 per dose in order to co-finance the vaccine with GAVI-eligible countries that apply and receive approval [4]. While the vaccine price is a key driver on the cost side, national governments and donors will also need to consider additional resources to support implementation costs associated with delivery of vaccine to a new target population that has not been routinely vaccinated previously. To date, while vaccine delivery costs for small-scale demonstration projects in India, Peru, Uganda, Vietnam [5] and Tanzania [6] have been reported, data are lacking on large-scale, country-wide implementation costs. Hence, information on the affordability of different HPV vaccine delivery strategies in LMICs is limited.

As part of developing Tanzania's national comprehensive strategy for cervical cancer prevention and control, the Ministry of Health and Social Welfare (MOHSW) requested technical assistance from WHO to estimate the service delivery costs of introducing HPV vaccine into the country. This request was also in response to a MOHSW agreement to accept a three-year donation of HPV vaccine from the manufacturer. To address this request, WHO and their consultants developed the Cervical Cancer Prevention and Control Costing (C4P) tool in order to facilitate the decision-making process of program managers and policy makers by generating information on the projected costs of introducing cervical cancer interventions. The WHO C4P tool consists of a HPV Vaccine Module and a Cervical Cancer Screening and Treatment Module. As the latter component is still under development, this paper will focus only on the HPV vaccination component of the tool.

This paper aims to present the purpose, definitions, methods, data sources and assumptions behind the generic WHO C4P tool to assist LMICs with planning and costing their nationwide HPV vaccination program. Furthermore, Tanzania's experience and cost results will be presented in piloting the WHO C4P tool to scale up prevention interventions as part of their national comprehensive cervical cancer prevention and control plan.

In the scenario examined, 1.6 million girls are fully vaccinated (that is, receive three doses) over five years out of a total target population of 2.4 million girls (five cohorts of ten-year-old girls in the five-year national program with phased roll-out during years one to two and national vaccination starting in year three for an estimated three-dose vaccine coverage of 65%.) Table 3 provides a summary of the expected outputs of introducing HPV vaccines in Tanzania.

The five-year cost of introducing a national phased-in HPV vaccine program during 2011 to 2015 in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011). This is equivalent to a financial cost of US$5.77 per fully immunized girl, excluding the vaccine cost.

Table 4 shows the breakdown of costs during the first five years of the vaccine introduction by activities which totals to US$31.5 million (with vaccines). Excluding procurement, the largest share of costs goes towards social mobilization and IEC, followed by service delivery. Figure 2 shows a pie chart of the financial costs breakdown by activities of introducing HPV vaccine in Tanzania during 2011 to 2015. These data show that substantial funding is required for HPV vaccine delivery efforts despite the fact the vaccine will be donated during the first three years.

Figure 3 shows the economic costs of HPV vaccine by cost component. The resource requirements over five years that include shared costs (for example, transport or salaries also used for other vaccines) are approximately US$58 million.

Table 5 shows the financial and economic costs per dose and FIG without and with vaccines during 2011 to 2015 in terms of financial and economic costs. Without the vaccine costs the financial costs per dose and per FIG are US$1.66 and US$5.77, respectively, while the economic costs (including salary costs of MOHSW personnel) per dose and per FIG are US$3.56 and US$12.40. The average cost per dose and FIG are higher if the vaccine costs are included, as shown in Table 5.

Table 6 shows an illustrative comparison using the WHO C4P tool of school-based and health facility-based scenarios in terms of financial introduction and recurrent costs per eligible girl. The introduction costs during the first three years of phased roll-out would be similar; however, the recurrent costs per dose and for three doses per eligible girl would be higher for a school-based compared to health facility-based delivery scenario because transportation costs of vaccines and personnel per diems will be higher for the outreach.

When countries expand their immunization schedule with a new vaccine such as HPV, they face initial costs to fund critical pre-introduction activities, as well as incremental system costs to deliver the vaccines on an ongoing basis. By using the WHO C4P, the Tanzania experience of introducing HPV vaccine through a phased school-based delivery strategy in all the 26 regions shows that the five-year recurrent total costs of introducing HPV vaccine (excluding vaccine cost) are around US$9.2 million, which is equivalent to US$5.77 per FIG to the government. These recurrent costs correspond to 0.7% of the government real expenditures on health, indicating that substantial ministry of health government resources, such as health personnel, are required to deliver the vaccine effectively. Actual resources required are dramatically higher when one considers the vaccine costs and shared costs included as part of the economic costs analysis, that is, approximately US$59 million over a five-year period.

This study shows that, other than procurement, the most important costs of service delivery are social mobilization/IEC and service delivery operational costs. Social mobilization and IEC activities are particularly important to ensure that broad coverage is achieved by informing the population about the benefits of HPV vaccination and supporting the service delivery strategy used. Governments need to plan ahead for these non-vaccine costs so that they will be financed adequately and human resources need to be re-allocated appropriately for the program to be successfully implemented in a sustainable and long-term manner.

To date, data availability on national HPV vaccination in LMICs is limited, which makes it difficult to validate the tool. However, the findings from the WHO C4P tool for Tanzania are consistent with existing information on recurrent costs from various small-scale demonstration projects from the Program for Appropriate Technology in Health (PATH) in India, Peru, Uganda and Vietnam [5] and the LSHTM project in Mwanza province in Tanzania [6]. Furthermore, the WHO C4P tool for Tanzania findings are also consistent with scale-up cost estimates for national HPV vaccination studies using the WHO C4P tool for Uganda [6], Bhutan and Rwanda based on actual HPV vaccine introduction with actual expenditure data (personal communication with responsible EPI officers from Bhutan and Rwanda)^a. These studies demonstrate that introduction costs for HPV vaccines are higher than those for existing vaccines such as meningitis A campaigns and combination DTP-HepB-Hib vaccine via routine infant EPI vaccination programs [8, 9] due to increased needs for IEC and social mobilization activities to sensitize the public about the benefits of HPV vaccines for adolescent girls.

From the nationwide-modeled experiences based on PATH demonstration projects, the average introduction costs per eligible girl are US$2.99 (range US$2.82 to US$3.07) and the recurrent costs to deliver three doses per eligible girl are US$4.17 (range US$3.51 to US$4.78) [5]. As HPV vaccine introduction requires building up a new delivery infrastructure, the costs are significantly higher. From the three available projected nationwide-modeled HPV vaccination costing studies in Tanzania, Uganda and Bhutan, the average cost is about US$3.00 per 10-year old girl.

The resource requirements of IEC activities are a large component of total costs since these are considered to be important aspects for a successful introduction of HPV vaccination, a new vaccine that targets a non-traditional population of adolescent girls. The population will need to be assured of its safety and benefits and be provided with an explanation of why this vaccination is given only to girls and not boys. The costs of IEC activities are calculated for the following activities: (1) sensitization meetings with community leaders to inform them of the benefits of the intended vaccination activities; (2) production of leaflets and posters on the benefits of HPV vaccinations to be placed by service providers in clinics, schools and public locations in their catchment areas; (3) design and production of radio and/or television announcements on the HPV vaccine for the population; and (4) briefings with writers, journalists, editors, publishers and other media personnel to inform them about the benefits of the vaccine. As HPV vaccination is scaled up in these countries, more IEC activities will be required, given that airing of radio and TV announcements will be more effective once the vaccination is scaled up nationally.

Past experience from the African region for delivery of other adolescent health interventions such as school deworming programs with benzimidazoles [10] and school-targeted treatment for Schistosoma mansoni [11] suggest lower cost estimates per child compared to delivering an adolescent vaccine. More recently, costing data is becoming available on the delivery and scaling up of sexual and reproductive health interventions through adolescent-friendly health services. Pilot testing of a WHO costing tool in Uganda in 2006 found unit costs per adolescent child ranging from US$4.50 for sexually transmitted infection (STI) treatment in a public primary health facility to US$19 for HIV counseling and testing in a non-governmental organization (NGO)-run facility [12]. Overall, however, accurate cost estimates of interventions delivered to young people are rare and more needs to be done to improve evaluations of the economic value of investments targeted at this age group [13].

In anticipation of these additional service delivery costs for HPV vaccines as an example for non-traditional vaccines, the GAVI Alliance is reviewing its current policy towards vaccine introduction grants and operational support for campaigns [14]. GAVI's introduction grant is a one-time cash grant to fund some of the activities associated with adopting a new vaccine in a country's national immunization program [15]. However, the vaccine introduction grant does not fund the total costs resulting from a new vaccine introduction. Governments and partners are expected to contribute additional funding in order to facilitate an effective introduction. Past experience has shown that governments have not always been able to quickly mobilize additional funding from their own budgets or development partners to fill these funding gaps. The WHO C4P tool could be used to assist countries in estimating the pre-introduction and incremental system costs to deliver the HPV vaccine.

Use of an early version of the Cervical Cancer Screening and Treatment Module of the WHO C4P tool demonstrates that the preliminary costs of scaling-up screening and treatment in Tanzania are estimated to be $12.1 million over five years. In the scenario examined, 1.2 million out of a target population of five million women are screened using visual inspection with acetic acid (VIA), while 17.4 thousand women out of 60 thousand VIA-positive women receive treatment. This estimate is based on screening at the health dispensary level and above and treatment at the health center level and above [16]. Completion of the Cervical Cancer Screening and Treatment Module of the WHO C4P tool will further contribute to the decision-making process.

Finally, HPV vaccines are not the only new vaccines being considered for introduction in LMICs. There are also pneumococcal and rotavirus vaccines as well as several older vaccines that have not yet been broadly adopted in developing countries. Although intended for national HPV vaccination costing and planning purposes, the economic cost results of the WHO C4P tool can be used as an input for cost-effectiveness analysis and/or budget impact analysis in order to assist countries in setting their priorities between competing vaccines or other cervical cancer control options. In-country cost estimates of the programmatic costs of delivering an adolescent vaccine and scaling up of cervical cancer screening and treatment interventions as an input for cost-effectiveness analysis are rare. For instance, a health and economic impact study of HPV vaccination and cervical cancer screening in five Eastern African countries would have benefited from a country-specific data collection and projection costing tool such as WHO C4P to estimate these programmatic costs [17] among other tools.

The financial delivery costs of nationwide HPV vaccination are higher than those of infant vaccines and can be substantial in resource-poor settings since it requires building up new delivery channels. As a consequence, governments need to plan ahead for these non-vaccine costs so that they will have adequate finances in place for vaccine introduction.

As GAVI's vaccine portfolio is expanding and countries are expected to introduce new vaccines at an increasing rate, it is recommended to include (partial) funding for operational health system costs in order assist GAVI eligible countries in introducing HPV vaccines. Together with other decision-making tools, the WHO C4P tool could facilitate both low- and middle-income countries in demonstrating their ability to deliver HPV vaccines nationwide to the target population in an effective, sustainable and affordable manner.

^aPersonal communication with Mr. Tandin Dorji, Chief Program Officer, Department of Public Health, Ministry of Health, Bhutan; and Mr. Maurice Gatera, Head of Vaccine Preventable Disease Division, Institute of HIV/AIDS Disease Prevention and Control, Rwanda Biomedical Center, Ministry of Health, Rwanda. Permission was obtained to quote their names.