Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries.

INTRODUCTION: There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. METHODS: Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). RESULTS: Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. CONCLUSION: HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

The projected cost-effectiveness and budget impact of HPV vaccine introduction in Ghana.

BACKGROUND: Cervical cancer is responsible for around one-quarter of all cancer deaths among Ghanaian women. Between 2013 and 2015, Ghana conducted a pilot of HPV vaccination among 10-14-year-old girls in four regions; however, the country has yet to introduce the vaccine nationally. This study projected the cost-effectiveness and budget impact of adding HPV vaccination into Ghana's national immunization program. METHODS: We used a proportional outcomes model (UNIVAC, version 1.4) to evaluate the cost-effectiveness of introduction with bivalent (Cervarix™) and quadrivalent (Gardasil®) vaccines from government and societal perspectives. Vaccine introduction was modeled to start in 2022 and continue over ten birth cohorts using a combined delivery strategy of school (80%) and community outreach (20%). We modeled vaccination in a single age cohort of 9-year-old girls vs. a multi-age cohort of 9-year-old girls (routine) and 10-14-year-old girls (one-time campaign) compared to no vaccination. Health outcomes included cervical cancer cases, hospitalizations, deaths, and disability-adjusted life years (DALYs). We applied a discount rate of 3% to costs and outcomes. All monetary units are reported in USD 2018. RESULTS: National HPV vaccination in Ghana was projected to be cost-effective compared to no vaccination in all scenarios evaluated. The most cost-effective and dominant strategy was vaccination among 9-year-old girls, plus a one-time campaign among 10-14-year-old with the bivalent vaccine ($158/DALY averted from the government perspective; 95% credible range: $19-$280/DALY averted). Projected average annual costs of the vaccine program ranged from $11.2 to $15.4 M, depending on strategy. This represents 11-15% of the estimated total immunization costs for 2022 ($100,857,875 based on Ghana's comprehensive Multi-Year Plan for Immunization, 2020-2024). DISCUSSION: Our model suggests that introducing HPV vaccination would be cost-effective in Ghana under any strategy when willingness-to-pay is at least 40% GDP per capita ($881). Inclusion of a one-time catch-up campaign is shown to create greater value for money than routine immunization alone but would incur greater program costs.

What works for human papillomavirus vaccine introduction in low and middle-income countries?

Since 2007, low and middle-income countries (LMICs) have gained experience delivering HPV vaccines through HPV vaccination pilots, demonstration projects and national programmes. This commentary summarises lessons from HPV vaccination experiences in 45 LMICs and what works for HPV vaccination introduction. Methods included a systematic literature review, unpublished document review, and key informant interviews. Data were extracted from 61 peer-reviewed articles, 11 conference abstracts, 188 technical reports, and 56 interviews, with quantitative data analysed descriptively and qualitative data analysed thematically. Key lessons are described under five themes of preparation, communications, delivery, coverage achievements, and sustainability. Lessons learnt were generally consistent across countries and projects and sufficient lessons have been learnt for countries to deliver HPV vaccine through phased national rollout rather than demonstration projects. However, challenges remain in securing the political will and financial resources necessary to implement successful national programmes.

Human papillomavirus (HPV) vaccine coverage achievements in low and middle-income countries 2007-2016.

INTRODUCTION: Since 2007, HPV vaccine has been available to low and middle income countries (LAMIC) for small-scale 'demonstration projects', or national programmes. We analysed coverage achieved in HPV vaccine demonstration projects and national programmes that had completed at least 6 months of implementation between January 2007-2016. METHODS: A mapping exercise identified 45 LAMICs with HPV vaccine delivery experience. Estimates of coverage and factors influencing coverage were obtained from 56 key informant interviews, a systematic published literature search of 5 databases that identified 61 relevant full texts and 188 solicited unpublished documents, including coverage surveys. Coverage achievements were analysed descriptively against country or project/programme characteristics. Heterogeneity in data, funder requirements, and project/programme design precluded multivariate analysis. RESULTS: Estimates of uptake, schedule completion rates and/or final dose coverage were available from 41 of 45 LAMICs included in the study. Only 17 estimates from 13 countries were from coverage surveys, most were administrative data. Final dose coverage estimates were all over 50% with most between 70% and 90%, and showed no trend over time. The majority of delivery strategies included schools as a vaccination venue. In countries with school enrolment rates below 90%, inclusion of strategies to reach out-of-school girls contributed to obtaining high coverage compared to school-only strategies. There was no correlation between final dose coverage and estimated recurrent financial costs of delivery from cost analyses. Coverage achieved during joint delivery of HPV vaccine combined with another intervention was variable with little/no evaluation of the correlates of success. CONCLUSIONS: This is the most comprehensive descriptive analysis of HPV vaccine coverage in LAMICs to date. It is possible to deliver HPV vaccine with excellent coverage in LAMICs. Further good quality data are needed from health facility based delivery strategies and national programmes to aid policymakers to effectively and sustainably scale-up HPV vaccination.

Feasibility of delivering HPV vaccine to girls aged 10 to 15 years in Uganda.

BACKGROUND: Cervical cancer is a leading cause of mortality among women in Uganda. The availability of the human papillomavirus (HPV) vaccine presents an opportunity to prevent cervical cancer. The Government of Uganda conducted a demonstration project exploring the feasibility of two delivery strategies. OBJECTIVE: To explore the feasibility of two HPV vaccine delivery strategies: 1) a stand-alone school-based strategy that selected girls based on their enrolment in grade 5 (known as the "grade-based" strategy; and 2) an age-based strategy that delivered the HPV vaccine based on the girls' age (10-year-olds). This strategy combined the delivery of the vaccine with the distribution of deworming medication and vitamin A through an existing Child Days Plus program. METHODS: A qualitative study that explored the feasibility of the two delivery strategies from the perspective of health workers, district leaders, and staff of the Uganda National Expanded Programme on Immunization, utilizing in-depth interviews and focus group discussions. RESULTS: Coverage data showed that more girls (88%) were vaccinated using the grade-based strategy and completed all three doses compared to those (73%) vaccinated using the age-based strategy. Health workers and teachers indicated that determining vaccination eligibility was easier by grade than by age and there were minor disruptions to health services and school programs during vaccinations, as reported by health workers and teachers using the grade-based strategy. CONCLUSION: HPV vaccine delivery at schools using grade eligibility was more feasible than selecting girls by age. Lessons learned in Uganda could be relevant for countries considering implementing HPV vaccinations.

Lessons learned from HPV vaccine delivery in low-resource settings and opportunities for HIV prevention, treatment, and care among adolescents.

BACKGROUND: Human papillomavirus (HPV) vaccines to prevent cervical cancer have become available in recent years and presented a new challenge to health systems, since they prevent a sexually transmitted virus and are most effective if they are delivered to young adolescent girls, a group not widely served by other health programs. Demonstration and pilot HPV vaccination programs undertaken in the past 7-8 years in low-resource settings have produced lessons that may be more broadly applied to other adolescent health interventions, particularly to those that attempt to reduce human immunodeficiency virus (HIV) infection. METHODS: A systematic literature review was undertaken to identify formal and informal evaluations of HPV vaccine use in low- and middle-income countries. Special attention was devoted to the detailed evaluations carried out on large demonstration projects in India, Peru, Uganda, and Vietnam. RESULTS: These lessons fall into 2 main categories: service delivery operations and community outreach and mobilization. Operational issues included venue and timing of vaccinations, definition of target population, micro-planning and coordination, integration with other services, and training. Community issues included consent, messages and channels, endorsement and support, and timing of mobilization efforts. DISCUSSION: Careful planning, good coordination across sectors and levels, and sensitive attention to the expressed needs for information and preferences for communication channels among youth, parents, and communities more broadly were among the key lessons that are relevant for HIV interventions, but many of the smaller details were also important. CONCLUSIONS: Applying or adapting these lessons to adolescent HIV services could accelerate effective program design and enhance success.

Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru, Uganda and Viet Nam.

OBJECTIVE: To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam. METHODS: Data were collected from a sample of facilities that participated in five demonstration projects for hpv vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US$). Exclusively project-related expenses and the cost of the vaccine were excluded. FINDINGS: The economic delivery cost per vaccine dose ranged from US$ 1.44 for integrated outreach in Uganda to US$ 3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US$ 1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI). CONCLUSION: The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services.

Upgrading public health programs for human papillomavirus prevention and control is possible in low- and middle-income countries.

Cancer is an important cause of premature death in low- and middle-income countries (LMIC). Two preventive tools are available that have the potential together to sharply decrease the impact of cervical cancer in LMIC. The combination of human papillomavirus (HPV) vaccination and cervical cancer screening within existing programs is possible. Although there is a great deal of concern about introducing and strengthening HPV prevention efforts in LMIC, recent projects have demonstrated feasibility. Thus, with appropriate prioritization and resources, HPV prevention can be introduced and scaled up. Comprehensive HPV prevention strategies, mainly those geared at preventing cervical cancer, should include both vaccination and screening. The integration of both screening and vaccination will save the most lives, and such strategies are endorsed by many international organizations. However, some vaccine and screening programs are financed almost entirely by special externally-based programs. These more closely resemble demonstration exercises than sustainable national programs. In order for successful demonstration projects to have a broad impact on prevention, sustainable national funding based on strong commitments is essential. There may be challenges to implementing HPV prevention programs, but none should be considered insurmountable. Many LMIC have successfully adopted an HPV prevention agenda despite prevailing pessimism. Failure to act on this issue can perpetuate inequity in sexually transmitted infection and cancer prevention. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings.

This descriptive qualitative study synthesizes health system and immunization financing assessments performed through formative research in India, Peru, Uganda, and Vietnam using a non-probability sample of national and sub-national stakeholders; and recommends appropriate and effective strategies for HPV vaccine delivery in low-resource settings. We conclude that maximum feasibility and acceptability and lowest cost for delivering HPV vaccine can be achieved by implementing through national immunization programs; by partnering with other sectors, such as education and maternal-child health; by strengthening existing human resources and cold chain infrastructures where needed; and finally, by considering schools for reaching the target population.

Sociocultural issues in the introduction of human papillomavirus vaccine in low-resource settings.

OBJECTIVES: (1) To synthesize sociocultural results from diverse populations related to vaccine decision-making, understanding of cervical cancer and its etiology, experience with previous vaccinations, human papillomavirus (HPV) vaccine concerns, and information needed to foster acceptance; (2) to contextualize findings in light of recent studies; and (3) to discuss implications for communication strategies to facilitate vaccine acceptance. DESIGN: Descriptive qualitative synthesis of sociocultural studies in 4 countries using iterative theme-based analyses. SETTING: Four developing countries: India, Peru, Uganda, and Vietnam. PARTICIPANTS: Criterion-based sample of 252 focus-group discussions and 470 in-depth interviews with children, parents, teachers/administrators, health workers/managers, and community/religious leaders. A knowledge, attitudes, and practices survey was administered to 879 children and 875 parents in Vietnam. RESULTS: We found that vaccine decision-making was primarily done by parents, with children having some role. Understanding of cervical cancer and HPV was limited; however, the gravity of cancer and some symptoms of cervical cancer were recognized. Vaccination and government-sponsored immunization programs were generally supported by respondents. Sentiments toward cervical cancer vaccines were positive, but concerns about quality of delivery, safety, adverse effects, and the effect on fertility were raised. Communities requested comprehensive awareness-raising and health education to address these concerns. CONCLUSION: Sociocultural studies help elucidate the complexities of introducing a new vaccine from the perspective of children, parents, and communities. Strategies for introducing the HPV vaccine should address community concerns through effective communication, appropriate delivery, and targeted advocacy to make the program locally relevant.