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  and the LSHTM project in Mwanza province in Tanzania . 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 , 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) . 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.
The WHO C4P tool in its current version has several limitations. First, depending on the countries' characteristics, additional sizable costs might be expected from a societal perspective that are not included in the WHO C4P tool, such as private costs to schoolgirls, parents and caregivers and additional costs for the cold chain. Variation in the incremental cost to the health system of vaccinating adolescent girls by different countries is expected and can potentially be explained by country characteristics, such as size of the country, population density and proximity of health facilities to schools, current infrastructure of schools and health facilities and national income level as well as the intensity of the HPV vaccine introduction effort (Levin et al. in preparation). Secondly, monitoring and evaluation costs are restricted to production of tally sheets and vaccination cards. In reality, additional quality control or evaluative measures, such as cost of administrative personnel to evaluate coverage levels might be required.
Past experience from the African region for delivery of other adolescent health interventions such as school deworming programs with benzimidazoles  and school-targeted treatment for Schistosoma mansoni  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 . 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 .
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 . 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 . 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 . 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  among other tools.