Background
Cervical cancer affected 570,000 women worldwide in 2018 and 311,000 died of the disease [
1]. Cervical cancer is currently the most common type of cancer affecting women in low- and middle-income countries (LMICs) [
2]. This is also the case in Mozambique, where 5,622 women were diagnosed with cervical cancer and 4,061 women died of the disease in 2017 [
3]. Cervical cancer has also been identified to be the most common type of cancer between 1991 and 2008 in the country’s main Central Hospital [
4]. However, due to underdiagnoses, any reported figure is very likely to be an underestimation of the real disease burden.
Human papillomavirus (HPV) is a necessary cause of cervical cancer [
5]. Specifically, HPV 16 and 18 are the two genotypes responsible for about 70% of cervical cancer cases [
6]. The development of safe and efficacious vaccines against the two high-risk HPV genotypes raised hopes of reducing the global incidence of cervical cancer. While most high-income countries progressively adopted publicly funded HPV vaccination programmes since 2006, few LMICs could afford its implementation due to the high vaccine price [
7,
8]. To improve access in LMICs, an agreement to reduce HPV vaccines’ price to US$5 per dose took place in 2011 between manufacturers and the GAVI Vaccine Alliance, formerly known as the Global Alliance for Vaccination and Immunisation [
9]. Only then, GAVI, national governments and other international organisations supported HPV vaccination programmes in LMICs with a yearly gross national income (GNI) per capita not higher than US$1,580 [
10,
11].
In sub-Saharan Africa, preliminary estimates suggest that, under the assumption of high coverage and lifelong protection, the introduction of the vaccine is expected to result in high health gains in terms of both number of cancer cases and disability-adjusted life years (DALYs) averted [
12]. However, even after high vaccine price reductions, one of the key issues associated with HPV vaccination is its cost of delivery and administration, particularly in rural and remote areas [
13,
14]. Despite the efforts made, the unsubsidised cost of HPV vaccination is still higher than the majority of vaccines. Its delivery is challenging as the target group for HPV vaccination (girls between nine and 13 years of age) [
6] differs markedly from the routine expanded programme on immunisation (EPI), which targets infants and young children [
15].
The challenge of reaching the HPV vaccination target group is the absence of an entry point at health facility level, calling for the need to reach the girls outside the health system
stricto sensu. Vaccination at schools has been suggested as an effective strategy to maximise both vaccine coverage [
16] and the number of fully-immunised girls (FIGs) [
17]. However, in LMICs some girls may be found absent from school on vaccination days, implying the need for establishing additional community strategies to maximise the reach [
18]. These outreach approaches require high level of resources to identify the target population, engage them, train health professionals, teachers and other stakeholders, and finally deliver the vaccine [
19‐
22].
In recognition of the high burden of cervical cancer in Mozambique, new efforts have been in place to reduce the disease burden in the country. Such efforts included a cervical cancer screening programme launched in 2009 [
23], the consolidation of a cancer registry based at the Maputo Central Hospital [
4], and the evaluation of introducing HPV vaccination to pre-adolescent girls as part of the national routine EPI by 2021. Under this framework, a demonstration programme was carried out in Mozambique consisting of vaccinating ten-year-old girls at schools, health facilities and communities in three districts: Manhiça, Manica and Mocímboa da Praia; south, centre and north of the country, respectively. The programme ran in two cycles, years 2014 and 2015, and was implemented as a three-dose schedule of Bivalent Cervarix® during the first year and a two-dose schedule during the second year; both providing a complete immunisation [
24]. The programme implementation in Manhiça district followed a school-based approach and was funded and supported by GAVI as part of the initiative to introduce HPV vaccination in LMICs [
25]. The Mozambican government funded the delivery in the two other districts [
24]. This study estimated the costs associated with the demonstration programme of HPV vaccination during the 2014 cycle in the Manhiça district, and developed an alternative cost scenario for future implementation.
Discussion
During the first vaccination cycle of the demonstration programme in Manhiça district, when three doses were administered, the average financial cost per dose was US$6.07 (US$17.59 economic). Our estimations were below the mean financial (US$8.74) and economic cost per dose (US$19.98) recently calculated in a study reporting the findings of 12 demonstration projects in different LMICs, ten of which were sub-Saharan African countries [
19]. However, our estimations of the average financial (US$17.95) and economic (US$52.29) cost per FIG were higher than most of those obtained by other published studies reporting estimates of similar HPV vaccine demonstration programmes in LMICs [
15,
20‐
22].
Nonetheless, cross-country comparisons should be made with caution. First, our estimations refer to the Manhiça demonstration programme and no scale-up projection for the introduction of the vaccine at a national level was computed due to limited data on key variables, such as reliable target population and number of schools. Second, there is a great cost variability across countries [
21]: the average financial cost per FIG ranged from US$2.49 in India, under a school-based delivery strategy and community outreach services, to US$20.36 in Vietnam, also under a school-based delivery strategy. However, two pilot projects evaluated in Tanzania are likely to be more comparable to the programme in Manhiça: population size and density were similar, both followed a school-based delivery strategy, achieved similar coverage levels to that in Manhiça (79 and 72%) and resulted in similar average financial cost per FIG (US$15.27 and US$19.17) but higher average economic costs per FIG (US$66 to US$78) due to higher transport and storage costs [
21,
22].
The high average financial cost per FIG in Manhiça (US$17.95) is mainly explained by the lower coverage rate achieved (77%) than most of other demonstration programmes, and by certain country characteristics, such as: (1) low population density [
19], (2) long distance between health facilities and schools, and (3) programme design with high intensity of resources devoted to the programme [
19].
The school-based delivery strategy has important implications in terms of coverage that critically affects the cost per FIG in low-income countries: (1) school-based vaccine programmes face poor planning, and (2) high percentage of school absenteeism and out-of-school girls are commonly reported [
13]. According to the Mozambican National Institute of Statistics, 2,974 ten-year-old girls lived in Manhiça district at the time of the first cycle [
24], but only 2,280 were enrolled at schools according to the school census. It implies that 694 girls (23.34% of the target population) could not be reached following a school-based approach, therefore reducing the coverage and increasing the cost per FIG. One possibility is to increase the coverage through community visits of outreach services to reach girls in remote settings [
37]. Assuming two community visits per health facility catchment area, and under a three-dose regime, the average economic cost per dose would decrease to US$17.11 as coverage increases (94%). However, the average economic cost per FIG would still remain high (US$52.03) due to the increased number of vaccines administered: procurement of US$77.52 and delivery of US$36.35. Alternatively, a reduction in the supervision team to one and the outreach team at schools to one vaccinator and one teacher would diminish the total cost to US$101,629 (17%) due to halving the vaccine delivery cost to US$14,683 and reducing supervision to US$7,218, allowing a reduction in the average financial cost per FIG to US$13.44 (US$43.26 economic cost). Finally, should the two-doses regimen have been implemented during the 2014 cycle, it would have allowed reducing the overall economic cost of the programme (US$90,128; 26%) due to reductions in the vaccine procurement (US$43,190; 32.76%) and delivery (US$19,578; 33.33%), yielding to a decrease in the average economic cost per FIG to US$37.89, thanks to savings in number of school visits. A combination of these three measures would reduce the average economic cost to US$15.53 per dose (US$5.00 financial) and to US$31.14 per FIG (US$9.99 financial).
Demonstration programmes in LMICs have been reported to be resource-intensive, but national vaccine implementation should involve substantial economies of scales [
19]. The Mozambican MoH projected an HPV vaccination cost of US$39 per FIG through the routine EPI schedule, lower than the one obtained in our study [
38]. However, it is important to note that Manhiça is dissimilar to other districts, due to its atypical socio-economic characteristics and circumstances related to its healthcare network privileged by the presence of a research institution. Thus, if Mozambique is to implement HPV vaccination targeted at ten-year-old girls in schools with minimal cold-chain requirements fulfilled, cuts must be made to the use of resources. First, reduction in the outreach team to one vaccinator and one teacher should be considered. Second, the need for subsistence support to the team as well as constant supervisory visits should be revisited. Further, despite the EPI, the MoH will most likely rely on implementation partners to support training, IEC and transport of the brigades in the field, and approaches to sustainability should be addressed.
The evaluation of alternative delivery mechanisms of HPV vaccination either under a health facility delivery strategy or as part of existing programmes (adolescent health programmes) would reveal which strategies are most efficient and less costly in the Mozambican context [
39,
40].
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