Implementation strategy and cost of Mozambique’s HPV vaccine demonstration project

Cost is an important determinant of successful implementation of healthcare programs [1, 2]. Health program implementation is associated with costs over and above the costs of the intervention itself and exclusion of implementation costs may bias economic evaluation results [3]. Costs are incurred during different phases of implementation and measuring and documenting implementation-phase-specific costs may provide useful information for national policy makers and health program managers engaged in decision making for adoption of health service innovations [4]. Such cost information is also useful to researchers attempting to standardize implementation research costing methods and produce generalizable study findings [5].

The human papilloma virus (HPV) is a common sexually transmitted organism that infects the anogenital and airway tracts where it may remain asymptomatic or manifest as warts, papillomatosis or cancer [6, 7]. Global HPV infections are associated with an estimated 50% of cancers in women and 5% in men, with varying burden depending on anatomical site. Anogenital sites are more significantly affected with proportions of more than 99% of cervical, 97% of anal, 70% of vaginal, 47% of penile and 40% of vulval cancer cases, compared to 47% of oropharynx and 11% of oral cavity cancer cases [8]. HPV types 16 and 18 account for more than 70% of invasive cervical carcinoma (ICC), the most significant cancer caused by the HPV [9]. Approximately 530,000 cases of cervical cancer occur in the world annually, with 50% progressing to death [10]. Low and middle-income countries (LMICs) in which screening programs and treatment options are limited, bear the brunt of the ICC burden with 85% of diagnosed cases and 87% of deaths [11].

The highest rates of age-standardized HPV incidence and mortality, 42.7 and 27.6 per 100,000 women respectively, are found in East Africa [12]. Mozambique has particularly high age standardized incidence rates (65.0 per 100,000) and mortality (49.2 per 100,000) and places second in the global ranking of cervical cancer burden [13]. Studies in Mozambique suggest that HPV is the main determinant of this large burden of cervical cancer: the prevalence of HPV, abnormal cervical cytology, and cervical neoplasia are as high as 40, 19, and 12% respectively, and HPV types 16 and 18 are present in 78% of biopsies from patients with cervical cancer [14].

Since its introduction in 2006, the HPV vaccine has demonstrated a high level of effectiveness for prevention of cervical cancer [15]. Three types of the vaccine exist: bivalent, quadrivalent and nonavalent. HPV vaccination has led to a decline in HPV-related disease in high-income countries [16‐18]. The World Health Organization (WHO) recommends adoption of HPV vaccination in LMICs, such as Mozambique, where cervical cancer is a major public health priority [19]. Consequently in 2011, Gavi, the Vaccine Alliance (Gavi) added the HPV vaccine to its list of financing-eligible vaccines, paving the way for its inclusion in national immunization programs (NIPs) in LMICs [20]. However, a challenge was encountered: girls ages 9–13 years, the target group for HPV vaccination, are not routinely targeted for immunization and interface with the health system is limited because adolescent-specific health services are minimal to non-existent in these settings [21]. As such Gavi’s initial HPV vaccine introduction strategy required countries to conduct demonstration projects to test possible delivery modalities prior to national rollout [22]. Many LMICs leveraged this opportunity and to date, 30 countries have conducted demonstration projects [23]. However, progress to national scale up of HPV vaccination has been slow: only six (of 30) countries had commenced national HPV vaccination programs by December 2017 [24, 25]. One barrier to national scale up of HPV vaccination programs is the higher delivery costs associated with setting up a new delivery model for the 9–13 year old target age group [26]. Nevertheless, current strategies to improve vaccination uptake [27, 28] coupled with evidence of long-term benefits from vaccine investment [29, 30] provide a strong rationale for allocation of resources to HPV vaccination programs which seem relatively expensive.

A recent review of the costs of introduction of HPV vaccines in LMICs concluded that country-specific HPV cost data were lacking and that there was a need for more information from country demonstration projects [31]. The aim of this study was to contribute to filling this gap in knowledge by conducting an in-depth analysis of the implementation costs of the demonstration project that was conducted in Mozambique. Specifically, we sought to estimate the cost of a fully immunized girl (FIG) and the costs of rolling out a similar program nationally.

We collected implementation cost data between January 2014 and March 2017 as part of a process evaluation of the Mozambique HPV demonstration project. The specific methods we utilized were: document review, participatory observation, and key informant interviews (KIIs) Additional file 1.

Forty-five personnel at the health facility, district, and national levels participated in the study, 27 from the Ministry of Health, six from the Ministry of Education, four from NGOs, three from multilateral agencies, three from research institutes, one from a bilateral organization, and one from a pharmaceutical company.

A summary of the number of health facilities, schools, and target population of eligible girls in each district is shown in Table 1.

The total implementation cost for the project in the three pilot districts was $523,602, 99.4% of which were direct medical costs. Note that costs for Manhiça district included Gavi subsidy funding while costs for the other two districts did not. In Table 2 the costs of implementing the HPV vaccine demonstration project activities are presented as total costs categorised into annual costs. Year one total project implementation costs were significantly higher than year two costs. The largest proportion in year one (23.8%) was personnel costs, while in year two most spending was on procurement (34%).

When costs were categorized by amounts spent in project locations including the central level and the three districts, the largest proportion were incurred in Manhiça accounting for 36.3% of total costs. Costs expended in Manica also amounted to a large proportion at 31.% while those spent at the central level and Mocimboa da Praia were the least and amounted to just 16.7% at each of the locations. At the central level, the largest implementation cost spending was on M&E activities, which accounted for 52% of the total costs, while procurement costs were the larger cost components in the districts accounting for 27, 34 and 27% in Manhiça, Manica da Mocimboa da Praia respectively.

The cost per FIG was $72 (CI: $62 - $83) in year one, $38 (CI: $37 - $40) in year two and $54 (CI: $49 - $61) for the whole project period. The cost of a FIG in each of the project districts in year 1, year 2, and whole project period were: Manhiça: $53 (CI: $41 - $63), $33 (CI: $29 - $43) and $42 (CI: $38 - $47); Manica: $66 (CI: $55 - $74), $33 (CI: $22 - $46) and $49 (CI: $40 - $54) and Mocimboa da Praia $373 (CI: $252 - $427), $123 (CI: $79 - $225) and $222 (CI: $136 - $361).

The cost of a FIG when the first year third dose implementation costs were excluded were: Year 1: $60 (CI: $50 - $72), Year 2: $38 (CI: $31 - $46) and for the whole two-year period $48 (CI: $42 - $55). When three of the total five doses that were given during the two-year period are excluded, and eligible girls each receive only one dose, the cost per FIG was; year one $30 (CI: $27 - $33)), year two $19 (CI:$15–$23) and year three $24 (CI:$22–$27).

The projected estimated costs for a 1 year two-dose and one-dose programs targeting all 10-year-old girls in Mozambique are presented in Table 3.

This study presents the resource use and costs of the Mozambique HPV vaccine demonstration project. The implementation strategy of the project from planning and preparation to project execution was used to guide the evaluation. The results show that important cost determinants were vaccine price, number of administered doses, program startup costs and the necessity for rigorous demand creation. Additionally, the cost per FIG is relatively high at 40–70% of per capita health expenditure [49] and is higher in the district with worse socio-economic conditions, fewer eligible girls and schools. A similar, primarily school-based national HPV vaccination program in Mozambique, would be a costly undertaking, however fewer doses could lead to a substantial reduction in costs.

All category-specific costs except those of procurement of vaccines and vaccine injection supplies were lower in year two of the project, with the increase in the category’s cost explained by the larger total number of girls who were vaccinated in the second year relative to the first year. HPV vaccine’s price per dose of $4.60 (excluding shipping costs) is significantly higher than the price per dose of older vaccines such as Bacillus Calmette–Guérin (BCG) at $0.11 and measles at $0.24. Moreover, its price per dose is even higher than recently introduced pneumococcal conjugate and rotavirus vaccines dose prices of $3.50 and $2.55 respectively [50]. The high vaccine cost in our study is consistent with findings from other studies which have found that vaccine costs are a major component of total HPV vaccination programs costs [51‐53]. Given that vaccine procurement (including injection supplies) costs often make up 50% of total national immunization programs’ vaccination costs [54], the findings from the current study raise concerns on the sustainability of HPV vaccines for Mozambique and other LMICs. Global level strategies to lower HPV vaccine pricing are needed to facilitate the vaccine’s adoption in these settings.

Personnel and demand creation costs were other major contributors to the total project costs. Both decreased significantly during the second year due to reduction in vaccine dosing from three to two doses, resulting in a week’s reduction of demand creation activities. Personnel costs accounted for 59% of total costs and consisted mainly of transportation costs and incentives for health workers to travel to schools to administer vaccines. These findings are important in the context of a potential future single dose HPV vaccination regimen [42‐44] which would significantly reduce transportation and health worker allowance costs. Lower vaccine dosing (one- and two-dose schedules) will make the vaccine’s introduction more feasible in Mozambique.

Higher year one costs for personnel, social mobilization, and M&E reflect start-up costs that are required when initiating a program. Due to economies of scale, these start-up costs are expected to remain the same or rise modestly in order to cover a larger number of girls in a national scale up. In addition, social mobilization costs were higher in the district with the highest vaccination coverage, meaning that if resources are available, such costs should be considered as an important investment to stimulate increased vaccine uptake. Our findings are consistent with those of a study from Rwanda, the first country to roll out the HPV vaccine nationally in Africa [55].

The high cost per FIG of $54, observed in this study is consistent with costs per FIG found in other costing studies conducted within the context of HPV vaccine demonstration projects in LMICs [31‐38]. Such expenditure on an individual recipient of the vaccine would amount to more than 50% of Mozambique’s current estimated health spending per capita of $92 [49]. The cost per FIG for the northern district was extremely elevated at $222 compared to $42.06 and $48.59 in for each of the other two districts. This is consistent with incremental implementation costs associated with the inefficiency of delivering health interventions in complex settings [2]. Our previously published process evaluation findings from this pilot project, demonstrated that distance and poverty were barriers to HPV vaccine delivery and uptake in the northern district. In this district approximately 50% of girls were not enrolled in schools and therefore, could not be reached with a school based vaccine delivery model [56]. National scale up of HPV vaccination in Mozambique will require an allowance for equity whereby poorer districts will need to be allocated higher funding to overcome the aforementioned barriers related to access. Moreover, immunization methods for increasing vaccination coverage in hard to reach populations, such as those recommended by WHO should be employed [57]. When the cost per FIG in the current study was extrapolated to a one-year countrywide two-dose program, the estimated total program cost of $18.2 m ($15.9 m - $20.7 m) was found to be relatively higher compared to annual costs for recently introduced new vaccines in Mozambique. Specifically, pneumococcal conjugate vaccine total program costs are $11 m while those for the rotavirus vaccine program are $16 m for cohorts of boys and girls while HPV vaccine would cover girls only. Nevertheless, program costs for a one-dose HPV vaccine would amount to half $9 m ($8 m - $10 m) the costs of a two-dose program, a value that is comparable to the cost of recently introduced national vaccination programs.

The results of this study should be interpreted in the context of parameter data limitations. While most cost inputs in this study were obtained from observational data, some inputs were based on health worker and teacher interviews. Specifically, time spent at schools by health workers was estimated (not directly measured) as was time spent by teachers organizing the HPV vaccination process in schools and observing vaccinated girls for adverse effects post immunization. Wages for both teachers and health workers were based on central level salary scales rather than actual district-level salaries. Fuel cost calculations did not consider distances but rather used uniform estimates based on money provided to all districts irrespective of number of schools or health facilities. A flat local to dollar currency exchange rate that did not account for inflation fluctuations that may have occurred during the period of the demonstration project was assumed in the study. Although these limitations may have led to both over- and under-estimation biases in the costs estimated, such biases are reflected in uncertainty estimates.

Program implementation is complex and cost is a key factor in successful implementation. This study provides a framework that other researchers might use to identify, measure and value costs of implementing HPV vaccine delivery strategies. Additionally, the results provide important cost information that may be utilized by decision makers at Mozambique’s Ministry of Health. Introducing the HPV vaccine in Mozambique will be a costly endeavor however cost reduction may be achieved through adoption of a one-dose vaccination schedule. Given the cost drivers, the country will need to consider cost saving strategies including negotiation of vaccine price and the potential for economics of scale to mitigate demand creation costs so that the national roll out of HPV vaccine can be both feasible and sustainable.