SUPPLEMENT ARTICLE
Lessons Learned From HPV Vaccine Delivery in Low-Resource Settings and Opportunities for HIV Prevention, Treatment, and Care Among Adolescents Vivien D. Tsu, PhD, MPH,* Tania Cernuschi, MSc,† and D. Scott LaMontagne, PhD, MPH*
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. Key Words: HPV vaccine, adolescent health, low-resource settings (J Acquir Immune Defic Syndr 2014;66:S209–S216)
From *PATH, Seattle, WA; and †GAVI Alliance Secretariat, Geneva, Switzerland. Supported in part by GAVI Alliance. The authors have no conflicts of interest to disclose. Correspondence to: Vivien D. Tsu, PhD, MPH, PATH, PO Box 900922, Seattle, WA 98109 (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
INTRODUCTION Cervical cancer affects more than 500,000 women each year, with about 85% of those new cases occurring in developing countries.1 Because persistent infection with human papillomavirus (HPV) is the primary cause of cervical cancer (and other less common anogenital and oropharyngeal cancers), the advent of HPV vaccines in 2006 represented both a major opportunity to prevent cervical cancer and a major challenge for traditional immunization programs.2,3 There are 2 HPV vaccines on the market—1 bivalent and 1 quadrivalent; both contain the HPV types (16 and 18) that account for about 70% of cervical cancers. The quadrivalent vaccine has 2 additional HPV types (6 and 11) that cause 90% of genital warts. Both vaccines have been registered in more than 120 countries and are prequalified by the World Health Organization (WHO) for purchase by United Nations agencies.4 The vaccines have shown high efficacy in preventing precancerous lesions, both in clinical trials2,3,5,6 and more recently in routine use.7–9 For the greatest impact, HPV vaccines need to reach young adolescent girls aged 9–13 years,4 before they initiate sexual activity and are exposed to HPV. A variety of barriers to reaching young adolescent girls were anticipated in both high- and low-resource settings as programs prepared to develop HPV vaccine delivery strategies.10–12 Both settings had to deal with a population that was generally healthy and had few contacts with the health care system and with a topic (the sexual transmission of HPV) that was culturally sensitive. There were general concerns about reaching girls, the possible need for continued future screening for lesions caused by HPV types not included in the vaccine, and the uncertainty about the duration of protection. However, in high-resource settings, other adolescent vaccines are already delivered, and nearly universal school attendance allows for efficient means to reach girls; also, insurance and financing schemes are relatively well established.13 In low- and middle-income countries (LMICs), immunization programs focus mainly on infant vaccines, and school delivery of health services, school enrollment, and attendance are variable,14 and sexuality and fertility have different cultural meanings.15,16 LMICs have campaign experience with single-dose vaccines for older children, but HPV vaccines currently require 3 doses over a 6-month period. There are few countries with robust national-scale adolescent health initiatives or programs on which to build, especially for young adolescents.17–19
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These concerns led to implementation of HPV vaccine demonstration projects to generate evidence about effective ways to reach young adolescent girls. PATH, an international global health NGO, conducted projects in collaboration with national immunization programs in 4 countries in Africa, Asia, and Latin America.20 Through various vaccine donation programs, nearly 20 smaller demonstration projects have also been carried out in LMICs.21–27 Although these demonstration programs have produced many useful lessons for HPV vaccines,28 the lessons may be more broadly applied to other adolescent health interventions, particularly for those that attempt to reduce human immunodeficiency virus (HIV) infection. There are some obvious similarities between HIV and HPV infection and prevention, but there are also some essential differences. Both programs share the challenge of reaching individuals before sexual transmission and of talking about the sensitive topic of sexual behavior. HPV is more easily transmitted than HIV, with any sexual contact (even skin to skin), and many girls have been infected with 1 or more types within the first few years of any sexual activity. Also, unlike HIV, there is no easy and inexpensive test that can accurately determine whether a girl has already been infected with HPV of the types in the vaccine, so programs must use initiation of sexual activity itself as the surrogate to signal the point when HPV vaccine effectiveness is likely to drop off. Hence, this drives HPV vaccine programs to focus on young adolescents (often those aged 10–12 years), while HIV prevention programs can benefit adolescents of any age and young adults who are still HIV negative. Although both programs target diseases that manifest themselves in the future, they have very different time frames for the benefits that will accrue from interventions: HPV vaccine prevents a cancer 25–30 years in the future, whereas HIV prevention results can be seen within the next 5–10 years. In this article, we consider lessons from the published literature on HPV vaccine experience to date that we believe are relevant to interventions that support HIV prevention, treatment, and care among adolescents in low-resource settings. These lessons fall into 2 main categories: service delivery operations, and community outreach and mobilization. Applying the learning from the HPV vaccine experience could amplify the impact of current and future efforts to reduce the burden of HIV among the 1.2 billion adolescents in the world today.29
METHODS Systematic evaluations from the PATH demonstration projects were carried out to learn about success of different strategies in terms of coverage,20 feasibility,30–32 acceptability,33–37 and costs.38 The methods used for these evaluations included household surveys to determine vaccine coverage and reasons for acceptance or nonacceptance of HPV vaccine, interviews and focus group discussions with parents and vaccinated girls to understand decision making and vaccine acceptability, interviews of health workers and observations of service delivery activities to determine feasibility, and
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micro-costing studies to estimate start-up and ongoing costs of vaccine delivery. In addition, a systematic literature review was conducted to identify articles describing actual delivery of HPV vaccine in LMICs with either formal evaluations or anecdotal lessons delineated. The search terms “immunization programs,” “HPV vaccines,” “pilot programs,” “demonstration,” and “vaccine introduction” were used to search PubMed and Popline, starting in 2007 through September 2013 and including languages other than English. Of 297 articles that were identified, only 11 dealt directly with HPV vaccine delivery programs in LMICs. The remaining articles focused on prevaccination acceptability and logistics or high-income countries or were secondary reviews of other published work. After reviewing the PATH documents and the published literature, the authors identified common themes and groupings. The lessons reported here are those considered relevant to adolescents and possibly applicable to HIV interventions for adolescents in LMICs.
RESULTS Service Delivery Operations Issues Venue and Timing of Vaccinations HPV vaccine delivery experience across a range of countries has demonstrated success with using schools as an effective place to reach young adolescents, especially those attending primary school (Table 1).20,22–24,26,39 Both governmentrun, community-based HPV vaccination programs and special donation programs that offered vaccine at schools to a wide age range noted high uptake and completion of the 3-dose series among those who started, ranging from 76% in Tanzania to nearly 100% in Vietnam (Table 1). Schools also provided a coordination mechanism to track administration and receipt of follow-up doses (doses 2 and 3).22,23,26,30,31 Because school programs required movement of health workers out of clinics, similar to outreach vaccinations, additional resources for transport and daily per diems for health workers were needed.30–32,38 One study noted that regular schedule interruption was temporary, occurred during just 3 brief time periods each year, and did not negatively impact routine vaccine coverage of infants.30 Where loss to follow-up did occur, school transfers and family migration were noted to have been contributing factors.20,22,23 The complexity of logistics and coordination of vaccine delivery was amplified for school-based HPV vaccination programs, but careful planning at national level and close micro-planning with health authorities and schools at local levels were noted as important contributors to program success.22–24,28,30–32,39 The scheduling of vaccination dates to be convenient to schools, taking into consideration examination periods, holidays, and other busy times, and to complete the 3-dose series within a single school calendar year improved program implementation, as well as uptake and completion of vaccination.23,26,28,31,32,39 In places where HPV vaccine was offered for a few days at the scheduled time for each dose (sometimes referred to as “pulsed delivery”), staff tended to report easier logistics for implementation and follow-up than Ó 2014 Lippincott Williams & Wilkins
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TABLE 1. HPV Vaccine Delivery Strategies and Uptake, LMICs, 2008–2011
Country (Reference)
Year
Bhutan22
2009
Bolivia22
2009 2010
Brazil26
2010–11
Cambodia22 2009 Cameroon22 2010 2009 Haiti22 India20 2009–10
Lesotho22 Nepal22,25
20,21
Peru
Rwanda39 South Africa24 Tanzania23
Uganda20
Vietnam20
Lead NGO/ MOH NGO NGO/ MOH Research hospital NGO/ MOH NGO NGO MOH
Strategy 9 schools
Eligible Female Population
No. Eligible or Target
Total Received 3 Doses, Administrative Report, N (%)
3-Dose Coverage, by Population-Based Survey
2721 (85)
NA
3739 (107) 27,597 (89)
NA NA
9–13 year-olds in schools
3200
57 schools 9–13 year-olds in schools 258 sites (schools + clinics) 9–13 year-olds at sites
3480 30,900
19 schools in research study Grades 6 and 7 in school
1574
1338 (85)
NA
1 government hospital 20 clinics 7 schools 279 schools + 399 clinics, campaign-style 258 schools + 273 clinics, routine delivery 47 sites (schools + clinics) 17 schools
2009–10
MOH
2009 20084
MOH NGO
20101 2007–083 2010–115 2011
NGO MOH MOH MOH
2011 2010–11
Provincial DOH NGO
2010–11
NGO
2008
MOH
67 schools in randomized trial 67 schools in randomized trial 195 schools + 41 clinics
2009
MOH
195 schools + 41 clinics
2008–09
MOH
2009
MOH
2008–09 2009–10 2008–09 2009–10
MOH MOH MOH MOH
222 schools + 28 integrated with health days 222 schools + 28 integrated with health days 38 schools 38 schools 34 clinics 34 clinics
24 sites (schools + clinics) 264 schools 163 clinics All schools in the country Outreach in the community 31 schools
clinics, child clinics, child
10–18 year-olds (employees’ children) 9–18 year-olds at clinics 9–13 year-olds in schools 10–14 year-olds at sites
2000
2029 (101)
NA
1600 3300 14,533
1033 (65) 2884 (87) 13,791 (95)
NA NA 77%–88%*
10–14 year-olds at sites
12,636
9864 (78)
68%–83%*
10–18 year-olds at sites 10–26 year-olds in schools 9–13 year-olds at sites Grade 5 in schools 11 year-olds at clinics Grade 6 12 year-olds out of school 9–12 year-olds in grades 4 and 5 Grade 6 at schools
40,000 1096
33,818 (84) 1089 (99)
NA NA
3000 13,677 10,075 94,141 4651 963
3164 (105) 10,963 (80) 6891 (68) 88,927 (95) 3180 (68) 938 (97)
NA 83% 53% NA NA NA
3352
2639 (79)
NA
12 year-olds at schools
2180
1572 (72)
NA
Grade 5 in schools and 10 year-olds out of school Grade 5 in schools and 10 year-olds out of school 10 year-olds at sites
3459
3038 (88)
91%
2835
2448 (86)
90%
2263
2388 (106)
53%
10 year-olds at sites
1923
1637 (85)
61%
Grade 6 at schools Grade 6 at schools 11 year-olds at clinics 11 year-olds at clinics
2412 1890 1507 1205
2012 1766 1399 1181
83% 96% 94% 99%
(83) (93) (93) (98)
*In India, coverage varied by geographic regions of urban, rural, or tribal areas.
in those places where vaccine was offered on a continuous basis.20,22–24,39 In addition, the routine (nonpulsed) delivery program implemented in India noted that more than 90% of all vaccines were taken up during the first month of offer, making regular follow-up visits less efficient.20 A few pilot programs delivered HPV vaccine primarily through local health centers, requiring girls and sometimes their parents to come to the facility to receive the necessary 3 doses. Such programs in Cameroon and Peru reported initial uptake of 83% and 76%, respectively, and 3-dose completion Ó 2014 Lippincott Williams & Wilkins
rates of 65% and 71%, respectively, demonstrating that both initial uptake and follow-up for completion of the 3-dose series had challenges (Table 1).20–22 Two donation programs used incentives with girls—t-shirt giveaways in Haiti and tracking bracelets in Nepal—to encourage completion of all 3 doses.22 In all school-based delivery schemes, except the randomized trial of delivery by age or grade in Tanzania, the nearest health facility to the school was also used as a place to catch girls who missed doses during school vaccination days or offer the vaccine to girls who were not enrolled or www.jaids.com |
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attending school.20,22,24 These additional opportunities, sometimes referred to as “mop up” vaccinations, were noted to be significant contributors to achieving high rates of overall coverage in South Africa.24 School-based programs in Bolivia (second year), India, Lesotho, Nepal (second year), Rwanda, Uganda, and Vietnam used additional community outreach to reach girls who were not enrolled or attending school (out-ofschool girls)20,22,39; the other school-based programs did not report any provision of vaccine to out-of-school girls. Peru reported that although there was no mechanism to track and find girls not attending school, a population-based survey conducted after vaccinations estimated that only about 0.3% were out of school among more than 8000 eligible girls in the region where vaccination occurred.21
Definition of Target Population Eligibility for HPV vaccine was based on schoolattending status, grade in school, and/or age. School-based programs used either age or grade as the primary determinant of eligibility (Table 1). In South Africa, both age and grade were used by selecting all girls in grades 4 and 5, as well as all girls aged 9–12 years in schools.24 All programs delivering vaccine through health facilities used age as the selection criterion for vaccination. Evaluation data from a few of the pilot programs noted that vaccine administration was logistically easier in schools when selecting girls based on their grade of enrollment, as age was often difficult to verify.20,24,31,39 There was no report from these initial programs of verifying the age of vaccinees at the time of each dose; instead, registers of eligible girls based on the program’s preset criteria were created before the vaccination program and then used to track girls’ receipt of each dose, in addition to vaccination cards (which only recorded age at the time of the first dose).24,31
Micro-planning and Coordination Close coordination and preparation for the exercise was noted to be a strong element in successful vaccine delivery, especially for programs that used schools as vaccination sites.22,24,30–32,39 Micro-planning, as done for routine immunization for infants, was observed to be critical in the demonstration projects in India, Peru, Uganda, and Vietnam. This micro-planning exercise also provided an opportunity to train health workers, providing them with a field guide for implementation, which reinforced learning, standardized delivery, and helped to maintain quality in the program’s administration.30–32 Involving the school sector in micro-planning facilitated coordination of the timing of vaccination days with the school schedule and helped map out which health facilities would cover which schools (PATH pilots only). In district- or region-wide programs, an individual health facility tended to cover only 2–4 nearby schools, thus easing the burden for delivery.31 In Rwanda, the creation of subcommittees for planning of vaccination, that included the education sector, was noted to be particularly helpful.39 In South Africa, coordination between the Departments of Health and Education at the district level included careful planning of vaccine storage at the local hospital, transportation of vaccine to schools, and vaccine administration by the school health teams.24
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Integration With Other Services The national introduction of HPV vaccine in Rwanda and the HPV vaccine demonstration programs by PATH were fully integrated into the routine program structures and operations of the national immunization programs within the participating districts.20,39 Unique to the program in 1 district of Uganda, HPV vaccine delivery was combined with semi-annual child health days, which distributed vitamin A, deworming, and supplemental vaccinations in the community,20,31 providing an example of service integration. Implementation costs from this program were half those incurred in the school-based program in Uganda.38 Integration with the provincial cervical cancer screening program was reported in the South African pilot, in which bags containing screening information were given to girls on the first vaccination dose.24 There are anecdotal reports that, in many areas, efforts to raise awareness about cervical cancer in preparation for vaccine programs also created demand for cervical screening services.
Training Training was critical to the preparation of staff to successfully implement the vaccination program, especially given the potentially sensitive cultural issues involved.22,30,31,39 Training curricula were customized for the audiences trained and their specific roles in the vaccination program—detailed for health workers, including the provision of a “field guide” to have as reference during program implementation, and less detailed for teachers. By and large, the methods included both participatory and didactic approaches and were supplemented by visual aids.30,31 Feedback from teachers during follow-up interviews suggested that teachers, in particular, appreciated the interactive training methods that were used. Having the opportunity to practice answering questions through role-play exercises and having materials especially designed for their communities made it easier for them to be effective resource people. Trainings lasted from one-half day to 3 days, depending on who was trained.28 Most school-based programs emphasized the critical role of training teachers to help inform students and parents and to assist in the logistics on days of vaccination in the classroom.22,30,31,39 Costing studies noted that training expenses accounted for 13%–43% of the proportion of startup financial costs of HPV vaccine delivery,38,40 and most programs reported that adequate financial resources are essential for effective training.22 A trade-off between cost of training and the magnitude and depth of the training was noted in Peru, particularly important when considering the question of replication and sustainability at a national scale.30
Community Outreach and Mobilization Issues Consent The use of written informed consent versus community consent was variable across vaccination programs. In general, programs implemented with a donation, such as from the Gardasil Access Program, required written informed consent from parents, and sometimes this form was several pages long.22,24 Demonstration programs in Peru, Uganda, and Ó 2014 Lippincott Williams & Wilkins
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Vietnam operated by the national EPI program, and the national program of Rwanda tended to use a community consenting, opt-out approach, as is done for other vaccines administered through routine government systems.20,39 Vietnam and Peru used a written consent the first year of their program, which raised suspicions among parents and was logistically difficult to manage; in the second year, this was modified to use either community consenting or a simple “parental authorization for services” form.21,28,30,32–34
Messages and Channels All pilot programs experienced a high level of acceptance, as indicated by the high levels of uptake of the vaccine in eligible populations, regardless of country.20,22,23,25,26,39 Several programs additionally evaluated motivators and factors that influenced parental decision making regarding vaccination.22,33–37,41,42 Protection against cervical cancer and expectation of a positive health benefit from vaccination were overwhelmingly the primary reasons for vaccination among parents surveyed in India, Peru, Tanzania, Uganda, and Vietnam.20,41 These were also motivators for girls accepting vaccine, as indicated by surveys with girls from Uganda, Vietnam, and Tanzania.35,37,41 Directly addressing parental concerns, identified before vaccination,15,16 with the communication activities and materials during the vaccination exercise was also emphasized as a key reason for high levels of acceptance of HPV vaccine in the community.22,33–36,41,42 Clear concise messages in locally understood terms were important.22,28,35,42 In Peru and Vietnam, it was particularly important to give parents adequate time to make a decision, as many parents did not immediately consent at first offer.33,34 Results from Tanzania suggested that this approach might have been beneficial, as the majority of parents and girls interviewed who were not vaccinated indicated they would agree to receive HPV vaccine if it were offered again.41 Research from Uganda and Vietnam suggested that the person a parent consulted with or received information from was more important than the specific education materials they received.36 All pilot programs reported that parents had concerns about vaccine safety and impact on future fertility, and that these concerns should be addressed in any communication activity or materials used before HPV vaccination.20,33–36,41,42 The communication modalities used to raise awareness and disseminate information for vaccine decision making were varied, as was the time in which these activities were conducted. Leaflets and posters were a common feature, as were radio announcements and other broadcasts in the community of vaccination dates and key messages.28,36,41,42 Meetings with parents at schools, health centers, or in the community were also conducted.28 Most programs conducted mobilization and sensitization activities before each dose of vaccine with the most intense activities occurring before dose 1. Announcements in church and use of key trusted persons, like religious or community leaders, to disseminate information were noted to be helpful.28,31,36 As with training costs, program implementation costs for social mobilization were significant, comprising nearly one-half of all start-up costs Ó 2014 Lippincott Williams & Wilkins
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in Uganda, two-thirds of the start-up costs in Peru, and fully three-quarters of the start-up costs in Vietnam.38
Endorsement and Support Significant involvement by and support from the national government were noted to be critical factors for program success and community uptake.20,30–32,34,39 The endorsement by government assured the credibility of the program, as most parents respected and trusted the work of the national immunization program as a whole.31,39 Having visible government endorsement through high-profile launches that sometimes even included the First Lady of the country were also reported to be of positive benefit.31 Vaccination programs that implemented immunizations through the staff who were routinely administering infant vaccines tended to work better, with fewer logistical complications, than those that hired separate staff or otherwise administered vaccinations outside the regular government EPI program.22 As noted earlier, other local leaders and persons of influence helped bring credibility to the vaccination program and influenced a broader positive environment for acceptability.22,31,36,39 Understanding who these persons may be and sensitizing them in advance of program implementation helped prepare them to provide key messages to the community. As a part of the local leader endorsement and support, education officials, teachers, school headmasters, and others affiliated with the education sector were helpful in creating an enabling environment to support the vaccination program, both before vaccinations and during immunization sessions.22,31–34,37,41,42 Crisis communication plans and managing rumors were important components of nearly all vaccination pilots. Programs with the strong involvement of the government gave particular attention to this issue.28,31,41 Having defined roles and clear messages enabled a rapid and effective response by respected and trusted officials when needed.
Timing of Mobilization Efforts Although not specifically evaluated in the published literature, descriptions of program implementation for HPV vaccinations seem to suggest different time frames for mobilization and sensitization from national level down to the local level. These are summarized in Table 2. In general, it is important to ensure far in advance, 6–9 months, that all the appropriate national level stakeholders are fully briefed and sensitized to build the foundation of strong government endorsement before vaccination planning. After that, a cascade of mobilization and sensitization occurs at district level
TABLE 2. Key Stakeholder Groups and Timing of Sensitization and Mobilization for HPV Vaccine Delivery Group National and local officials National and regional CSO leaders Local influential groups Heads of individual schools Parents and girls
How Far Ahead to Engage (mo) 6–9 3–6 3 3 1
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(3–6 months before), local level trainings, including teachers and schools (2–3 months before), and community sensitizations and awareness-raising activities at least 4 weeks before the administration of the first dose.28
DISCUSSION HPV vaccine delivery has several characteristics that make the lessons derived from it particularly relevant to interventions to prevent HIV infection among adolescents, and perhaps to a lesser extent to serve the needs of the subgroup of those already infected. Few other health interventions address young adolescents—a group that has been relatively neglected in HIV prevention programs, but among whom prevention messages could pay off the most. Like HIV, HPV vaccine has obvious associations with sensitive sexual issues and also deals with consequences that may be perceived as distant in the future, although AIDS is much closer in time than cervical cancer and more visible. Because HPV vaccine is new and has attracted a lot of attention, we are fortunate to have some intensive evaluations that have yielded lessons across many different geographic, social, religious, linguistic, and cultural settings.
Operational Lessons Relevant to HIV Services The relevance of operational lessons drawn from the HPV vaccine experience (which might also fit the category called “program enablers” in the UNAIDS investment framework43) depends in part on the nature of the intervention. To the extent that HIV interventions are medical and outpatient (such as a vaccine or other prophylactic medication that requires health worker administration), the evidence about schools as a good venue is encouraging. Although enrollment rates in developing countries vary, the heavy emphasis on schoolbased delivery for HPV vaccine reflects recent transformations: attendance rates for girls in primary schools have been increasing rapidly,14 as countries invest more in economic development and expand access to universal primary education. HPV vaccine programs show that schools can be an effective place to reach young adolescents, including with brief interventions that require follow-up once or twice during the school year. We did not find the problems identified by Plummer et al44 in a qualitative study in Tanzania—authoritarian and abusive teachers, high rates of school absenteeism and dropouts—to be major obstacles, but perhaps that was because of the episodic nature of the demands on teachers. School delivery of health services requires careful planning and coordination with education officials at all levels, ensuring that teachers are engaged and prepared for the roles expected of them, and fitting the timing of interventions to the school calendar of holidays and examinations; the same lessons will certainly apply to HIV interventions. Time and cost implications of school delivery also require careful consideration. For equity reasons, school programs may have to be accompanied by initiatives for non–school-going adolescents, such as outreach or clinicbased service delivery. Defining the target population is important for any intervention, both for implementation and for subsequent
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monitoring and evaluation. If the intervention is age sensitive (as it is for HPV vaccine), then it will be critical to determine the extent to which approximate age is known or can be determined and documented. Although some countries have made progress with birth registration and identity documents, it seems that there are still many younger generations of schoolgoers who do not know their ages. In sub-Saharan Africa, only 41% of births were registered in the 2006–2011 period.45 With classrooms still encompassing a wide range of student ages, along with the natural variation in social maturing, it is a challenge to provide age-appropriate information on topics such as sexuality and safe sexual practices, and an operational challenge to reach across different classrooms to group children of similar ages. This might be more critical for HIV-related information than it was for HPV vaccination, which was less dependent on social maturity levels in shaping its messages. District-level micro-planning has been particularly well developed for immunization activities,46 but the techniques are useful for other health activities as well and were particularly appropriate for the pulsed nature of HPV vaccines. The coordination between the health and education sectors that was so critical for school-based HPV vaccine delivery would likely be important for HIV activities that might draw not only on multiple units within health ministries but also other ministries like youth, education, labor, and finance, as well as nongovernmental or community-based organizations that reach adolescents. It was apparent from the experience with Child Health Days in Uganda that combining HPV vaccine delivery with other interventions that were being done in the community was a cost-effective approach.31,38 As long as the same health staff were involved, there was at least overlap (if not an exact match) of the target groups, and the length of time needed for the new intervention did not significantly impact the other activities, then integration could be very beneficial. Such combinations save time on planning and travel, save transport costs, and share costs of social mobilization.38 The same could apply to HIV interventions, as long as the frequency of the HIV intervention matches the timing of the intervention it is combined with and care is taken to ensure that no stigma will accrue to the other interventions from the HIV message. The low level of knowledge on cervical cancer and HPV found in baseline formative research on the part of health workers and teachers,15,16,47–49 let alone community members, prompted governments to provide detailed training to them to ensure that they would be able to answer questions from parents, girls, and other community members.30,31 Training adults to relate to the concerns and language of adolescents is something that HIV/AIDS programs and pregnancy prevention programs have already encountered.50,51 Using participatory methods to train teachers may also help model for them how to use such methods with adolescents who are transitioning from passive, rote learners to active, questioning learners.
Community Outreach and Mobilization Lessons Community outreach and mobilization lessons from the HPV vaccine experience are highly relevant to HIV services, Ó 2014 Lippincott Williams & Wilkins
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especially preventive services where stigma and denial may be at play, such as voluntary counseling and HIV testing. This may be a particular issue when deciding what kind of consent for services is needed for adolescents. As is the case with family planning for older adolescents, there are issues of stigma, privacy, and autonomy for HIV programs. These have been less evident in the experience with HPV vaccines because they have involved mainly young prepubescent adolescents aged 10–12 years. Local customs around consent for other interventions will set the tone for HIV interventions, as they did for HPV vaccine. One of the most important lessons was that if the intervention is singled out for special requirements, it will raise suspicions and concern that the government has reservations or the intervention is experimental.30 The process of community mobilization and the methods used for HPV vaccinations has relevance for the delivery of HIV services. Preparing and using materials for parents that directly answer the questions they have, often generated through previous formative research, helped to focus key messages for informed decision making. One of these messages was that the intervention, in this case HPV vaccination, was endorsed by the government. Using appropriate channels where parents receive information, often from a trusted source like a health worker or teacher, is even more important where young adolescents are involved and may enhance the effectiveness of existing community awareness activities related to HIV prevention, often designed for older adolescents rather than their parents.52 There is no real parallel in HPV vaccination programs for the level of stigma that might attach to adolescent disclosure of positive HIV status, but the same underlying principles of building broad community support, including addressing parental concerns, should apply.
Limitations Although there are now a diverse set of countries for which lessons from HPV vaccinations for young adolescent girls have been summarized, our synthesis of these is constrained by the limited amount of published literature. Most of the articles reviewed were generated from 1 large 4-country project. However, similar results were found from other country experiences, suggesting common themes are emerging. The literature is also deficient in the number of rigorous evaluations conducted from either pilots or national scale-up of HPV vaccinations in LMICs, although more than 30 countries and territories have such experience. The general target of HPV vaccination programs in low-resource settings has been young adolescents, and therefore, the application of lessons working with this population may be less relevant for HIV interventions directed toward older adolescents.
CONCLUSIONS Despite the huge amount of attention that has been devoted to prevention and treatment services related to HIV/ AIDS, there are still many unanswered questions related to the special needs of adolescents, and particularly young Ó 2014 Lippincott Williams & Wilkins
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adolescents.53 The delivery of HPV vaccines, one of the few health interventions specifically targeted at young adolescents, provides an opportunity to see in action how a service with some similar characteristics has worked in low-resource settings. Some of the HPV vaccine lessons are common sense (but have not been well documented before), whereas others have surprised skeptics who predicted bigger problems with acceptability and logistics than were actually encountered. 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 most significant lessons that are relevant for HIV interventions, but many of the smaller details were also important, and applying or adapting them to adolescent HIV services could accelerate effective program design and enhance success.
ACKNOWLEDGMENTS The authors thank Susan Kasedde for helpful comments on the article, Jane Goett at PATH and Celina Hanson at GAVI for their assistance with the literature review, and David Oxley at PATH for administrative support. REFERENCES 1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917. 2. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356: 1915–1927. 3. Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374: 301–314. 4. World Health Organization. Human papillomavirus vaccines: WHO position paper. Wkly Epidemiol Rec. 2009;15:118–131. 5. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 viruslike particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95: 1459–1466. 6. Roteli-Martins CM, Naud P, De Borba P, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012;8:390–397. 7. Brotherton JM, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet. 2011;377:2085–2092. 8. Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11:227. 9. Rana MM, Huhtala H, Apter D, et al. Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: cancer registry-based follow-up. Int J Cancer. 2013;132:2833–2838. 10. Kane MA, Sherris J, Coursaget P, et al. Chapter 15: HPV vaccine use in the developing world. Vaccine. 2006;24:S3/132–139. 11. Sherris J, Friedman A, Wittet S, et al. Chapter 25: education, training, and communication for HPV vaccines. Vaccine. 2006;24:S3/210–218. 12. World Health Organization and United Nations Population Fund. Preparing for the Introduction of HPV Vaccines: Policy and Program Guidance for Countries. Geneva, Switzerland: WHO; 2006. 13. Principi N, Esposito S. Adolescents and vaccines in the western world. Vaccine. 2013;31:5366–5374.
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14. Global Education Digest 2012-Interactive Data Tool. UNESCO Institute for Statistics. Available at: http://www.uis.unesco.org/Education/Pages/ ged-2012-visualization.aspx. Accessed January 22, 2014. 15. Katahoire A, Jitta J, Kivumbi G, et al. An assessment of the readiness for introduction of the HPV vaccine in Uganda. Afr J Reprod Health. 2008; 12:159–172. 16. Jacob M, Mawar N, Menezes L, et al. Assessing the environment for introduction of human papillomavirus vaccine in India. The Open Vaccin J. 2010;3:96–107. 17. United Nations Population Fund (UNFPA). State of World Population 2013: Motherhood in Childhood, Facing the Challenge of Adolescent Pregnancy. New York, NY: UNFPA; 2013. 18. Bearinger LH, Sieving RE, Ferguson J, et al. Global perspectives on the sexual and reproductive health of adolescents: patterns, prevention, and potential. Lancet. 2007;369:1220–1231. 19. Tylee A, Haller D, Graham T, et al. Youth-friendly primary-care services: how are we doing and what more needs to be done? Lancet. 2007; 369:1565–1573. 20. LaMontagne DS, Barge S, Le NT, et al. Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middleincome countries. Bull World Health Organ. 2011;89:821–830B. 21. Penny M, Bartolini R. Evaluation of demonstration project 2010: health facility based immunization of 10 year old girls with HPV vaccine; part I: how does offering HPV vaccine in the health facility to 10 year old girls compare with a school based approach? Technical research report submitted to PATH; 2011. 22. Ladner J, Besson MH, Hampshire R, et al. Assessment of eight HPV vaccination programs implemented in lowest income countries. BMC Public Health. 2012;12:370. 23. Watson-Jones D, Baisley K, Ponsiano R, et al. Human papillomavirus vaccination in Tanzanian schoolgirls: cluster-randomized trial comparing 2 vaccine-delivery strategies. J Infect Dis. 2012;206:678–686. 24. Moodley I, Tathiah N, Mubaiwa V, et al. High uptake of Gardasil vaccine among 9-12-year-old schoolgirls participating in an HPV vaccination demonstration project in KwaZulu-Natal, South Africa. S Afr Med J. 2013;103:313–317. 25. Singh Y, Shah A, Singh M, et al. Human papilloma virus vaccination in Nepal: an initial experience. Asian Pac J Cancer Prev. 2010;11:615–617. 26. Fregnani JH, Carvalho AL, Eluf-Neto J, et al. A school-based human papillomavirus vaccination program in barretos, Brazil: final results of a demonstrative study. PLoS One. 2013;8:e62647. 27. Axios International. The Gardasil Access Program. Available at: http://www. gardasilaccessprogram.org/section/177. Accessed November 25, 2013. 28. PATH. Implementing HPV Vaccination Programs: Practical Experience From PATH. Seattle, WA: PATH; 2011. Cervical Cancer Prevention: Practical Experience Series. 29. Progress for children: A report card on adolescents. United Nations Children’s Fund, Number 10, April 2012. Available at: http://www. unicef.org/media/files/PFC2012_A_report_card_on_adolescents.pdf. Accessed November 25, 2013. 30. Penny M, Bartolini R, Mosqueira NR, et al. Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru. Vaccine. 2011;29:5022–5030. 31. Mugisha E, LaMontagne DS, Katahoire AR, et al. Feasibility of delivering HPV vaccine to girls aged 10 to 15 years in Uganda. Afr Health Sci. Provisional acceptance, August 26, 2013. In press. 32. LaMontagne DS, Nghi NQ, Nga LT, et al. Feasibility of HPV vaccination in Vietnam: evidence from a government-implemented demonstration program. BMC Public Health. 2013. 33. Bartolini RM, Winkler JL, Penny ME, et al. Parental acceptance of HPV vaccine in Peru: a decision framework. PLoS One. 2012;7:e48017. 34. Cover JK, Nghi NQ, LaMontagne DS, et al. Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination. BMC Public Health. 2012;12:629.
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35. Paul P, LaMontagne DS, Nga LT. Knowledge of cervical cancer and HPV vaccine post-vaccination among mothers and daughters in Vietnam. Asian Pac J Cancer Prev. 2012;13:2587–2592. 36. Galagan SR, Paul P, Menezes L, et al. Influences on parental acceptance of HPV vaccination in demonstration projects in Uganda and Vietnam. Vaccine. 2013;31:3072–3078. 37. Katahoire A, Murokora D, Arube-Wani J, et al. Acceptability of HPV vaccine among young adolescent girls in Uganda: young people’s perspectives count. Int J Child Adol Health. 2013;6:211–220. 38. Levin CE, Minh HV, Odaga J, et al. Incremental costs of strategies to deliver human papillomavirus vaccine to young adolescent girls in Peru, Uganda and Vietnam. Bull World Health Organ. 2013;91:585–592. 39. Binagwaho A, Wagner CM, Gatera M, et al. Achieving high coverage in Rwanda’s national human papillomavirus vaccination programme. Bull World Health Organ. 2012;90:623–628. 40. Quentin W, Terris-Prestholt F, Changalucha J, et al. Costs of delivering human papillomavirus vaccination to school girls in Mwanza region, Tanzania. BMC Med. 2012;10:137. 41. Watson-Jones D, Tomlin K, Remes P, et al. Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in Tanzania: a case control study. PLoS One. 2012;7:e45231. 42. Wamai RG, Ayissi CA, Oduwo GO, et al. Assessing the effectiveness of a community-based sensitization strategy in creating awareness about HPV, cervical cancer and HPV vaccine among parents in North West Cameroon. J Community Health. 2012;37:917–926. 43. UNAIDS. Investing for Results. Results for People. A People-Centered Investment Tool Towards Ending AIDS. Geneva, Switzerland: UNAIDS; 2012. Available at: http://www.unaids.org/en/media/unaids/contentassets/ documents/unaidspublication/2012/JC2359_investing-for-results_en.pdf. Accessed November 25, 2013. 44. Plummer ML, Wight D, Wamoyi J, et al. Are schools a good setting for adolescent sexual health promotion in rural Africa? A qualitative assessment from Tanzania. Health Educ Res. 2007;22:483–499. 45. UNICEF. State of the World’s Children. New York, NY: UNICEF; 2013. Available at: http://www.unicef.org/sowc2013/. Accessed November 15, 2013. 46. World Health Organization and UNICEF. Microplanning for Immunization Service Delivery Using the Reaching Every District (RED) Strategy. Geneva, Switzerland: World Health Organization; 2009. Available at: http://www.who.int/immunization/sage/9_Final_RED_280909.pdf. Accessed November 17, 2013. 47. Bingham A, Drake JK, LaMontagne DS. Sociocultural issues in the introduction of human papillomavirus vaccines in low-resource settings. Arch Pediatr Adolesc Med. 2009;163:455–461. 48. Bartolini RM, Drake JK, Creed-Kanashiro HM, et al. Formative research to shape HPV vaccine introduction strategies in Peru (Investigación formativa para diseñar estrategias para la introducción de la vacuna contra el VPH en el Perú). Salud Pública de Méx. 2010;52:226–233. 49. Nghi NQ, LaMontagne DS, Bingham A, et al. Human papillomavirus vaccine introduction in Vietnam: formative research findings. Sex Health. 2010;7:262–270. 50. WHO. Making Health Services Adolescent Friendly: Developing National Quality Standards for Adolescent Friendly Health Services. Geneva, Switzerland: WHO; 2012. 51. Kirby DB, Laris BA, Rolleri LA. Sex and HIV education programs: their impact on sexual behaviors of young people throughout the world. Adolesc Health. 2007;40:206–217. 52. Napierala Mavedzenge SM, Doyle AM, Ross DA. HIV prevention in young people in sub-Saharan Africa: a systematic review. J Adolesc Health. 2011;49:568–586. 53. WHO. Review of the Social Determinants and the Health Divide in the WHO European Region: Final Report. Copenhagen, Denmark: WHO; 2013. Available at: http://www.euro.who.int/__data/assets/pdf_file/0006/ 215196/Review-of-social-determinants-and-the-health-divide-in-the-WHOEuropean-Region-final-report-Eng.pdf. Accessed January 21, 2014.
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Lessons Learned From HPV Vaccine Delivery in Low-Resource Settings and Opportunities for HIV Prevention, Treatment, and Care Among Adolescents Vivien D. Tsu, PhD, MPH,* Tania Cernuschi, MSc,† and D. Scott LaMontagne, PhD, MPH*
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. Key Words: HPV vaccine, adolescent health, low-resource settings (J Acquir Immune Defic Syndr 2014;66:S209–S216)
From *PATH, Seattle, WA; and †GAVI Alliance Secretariat, Geneva, Switzerland. Supported in part by GAVI Alliance. The authors have no conflicts of interest to disclose. Correspondence to: Vivien D. Tsu, PhD, MPH, PATH, PO Box 900922, Seattle, WA 98109 (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
INTRODUCTION Cervical cancer affects more than 500,000 women each year, with about 85% of those new cases occurring in developing countries.1 Because persistent infection with human papillomavirus (HPV) is the primary cause of cervical cancer (and other less common anogenital and oropharyngeal cancers), the advent of HPV vaccines in 2006 represented both a major opportunity to prevent cervical cancer and a major challenge for traditional immunization programs.2,3 There are 2 HPV vaccines on the market—1 bivalent and 1 quadrivalent; both contain the HPV types (16 and 18) that account for about 70% of cervical cancers. The quadrivalent vaccine has 2 additional HPV types (6 and 11) that cause 90% of genital warts. Both vaccines have been registered in more than 120 countries and are prequalified by the World Health Organization (WHO) for purchase by United Nations agencies.4 The vaccines have shown high efficacy in preventing precancerous lesions, both in clinical trials2,3,5,6 and more recently in routine use.7–9 For the greatest impact, HPV vaccines need to reach young adolescent girls aged 9–13 years,4 before they initiate sexual activity and are exposed to HPV. A variety of barriers to reaching young adolescent girls were anticipated in both high- and low-resource settings as programs prepared to develop HPV vaccine delivery strategies.10–12 Both settings had to deal with a population that was generally healthy and had few contacts with the health care system and with a topic (the sexual transmission of HPV) that was culturally sensitive. There were general concerns about reaching girls, the possible need for continued future screening for lesions caused by HPV types not included in the vaccine, and the uncertainty about the duration of protection. However, in high-resource settings, other adolescent vaccines are already delivered, and nearly universal school attendance allows for efficient means to reach girls; also, insurance and financing schemes are relatively well established.13 In low- and middle-income countries (LMICs), immunization programs focus mainly on infant vaccines, and school delivery of health services, school enrollment, and attendance are variable,14 and sexuality and fertility have different cultural meanings.15,16 LMICs have campaign experience with single-dose vaccines for older children, but HPV vaccines currently require 3 doses over a 6-month period. There are few countries with robust national-scale adolescent health initiatives or programs on which to build, especially for young adolescents.17–19
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These concerns led to implementation of HPV vaccine demonstration projects to generate evidence about effective ways to reach young adolescent girls. PATH, an international global health NGO, conducted projects in collaboration with national immunization programs in 4 countries in Africa, Asia, and Latin America.20 Through various vaccine donation programs, nearly 20 smaller demonstration projects have also been carried out in LMICs.21–27 Although these demonstration programs have produced many useful lessons for HPV vaccines,28 the lessons may be more broadly applied to other adolescent health interventions, particularly for those that attempt to reduce human immunodeficiency virus (HIV) infection. There are some obvious similarities between HIV and HPV infection and prevention, but there are also some essential differences. Both programs share the challenge of reaching individuals before sexual transmission and of talking about the sensitive topic of sexual behavior. HPV is more easily transmitted than HIV, with any sexual contact (even skin to skin), and many girls have been infected with 1 or more types within the first few years of any sexual activity. Also, unlike HIV, there is no easy and inexpensive test that can accurately determine whether a girl has already been infected with HPV of the types in the vaccine, so programs must use initiation of sexual activity itself as the surrogate to signal the point when HPV vaccine effectiveness is likely to drop off. Hence, this drives HPV vaccine programs to focus on young adolescents (often those aged 10–12 years), while HIV prevention programs can benefit adolescents of any age and young adults who are still HIV negative. Although both programs target diseases that manifest themselves in the future, they have very different time frames for the benefits that will accrue from interventions: HPV vaccine prevents a cancer 25–30 years in the future, whereas HIV prevention results can be seen within the next 5–10 years. In this article, we consider lessons from the published literature on HPV vaccine experience to date that we believe are relevant to interventions that support HIV prevention, treatment, and care among adolescents in low-resource settings. These lessons fall into 2 main categories: service delivery operations, and community outreach and mobilization. Applying the learning from the HPV vaccine experience could amplify the impact of current and future efforts to reduce the burden of HIV among the 1.2 billion adolescents in the world today.29
METHODS Systematic evaluations from the PATH demonstration projects were carried out to learn about success of different strategies in terms of coverage,20 feasibility,30–32 acceptability,33–37 and costs.38 The methods used for these evaluations included household surveys to determine vaccine coverage and reasons for acceptance or nonacceptance of HPV vaccine, interviews and focus group discussions with parents and vaccinated girls to understand decision making and vaccine acceptability, interviews of health workers and observations of service delivery activities to determine feasibility, and
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micro-costing studies to estimate start-up and ongoing costs of vaccine delivery. In addition, a systematic literature review was conducted to identify articles describing actual delivery of HPV vaccine in LMICs with either formal evaluations or anecdotal lessons delineated. The search terms “immunization programs,” “HPV vaccines,” “pilot programs,” “demonstration,” and “vaccine introduction” were used to search PubMed and Popline, starting in 2007 through September 2013 and including languages other than English. Of 297 articles that were identified, only 11 dealt directly with HPV vaccine delivery programs in LMICs. The remaining articles focused on prevaccination acceptability and logistics or high-income countries or were secondary reviews of other published work. After reviewing the PATH documents and the published literature, the authors identified common themes and groupings. The lessons reported here are those considered relevant to adolescents and possibly applicable to HIV interventions for adolescents in LMICs.
RESULTS Service Delivery Operations Issues Venue and Timing of Vaccinations HPV vaccine delivery experience across a range of countries has demonstrated success with using schools as an effective place to reach young adolescents, especially those attending primary school (Table 1).20,22–24,26,39 Both governmentrun, community-based HPV vaccination programs and special donation programs that offered vaccine at schools to a wide age range noted high uptake and completion of the 3-dose series among those who started, ranging from 76% in Tanzania to nearly 100% in Vietnam (Table 1). Schools also provided a coordination mechanism to track administration and receipt of follow-up doses (doses 2 and 3).22,23,26,30,31 Because school programs required movement of health workers out of clinics, similar to outreach vaccinations, additional resources for transport and daily per diems for health workers were needed.30–32,38 One study noted that regular schedule interruption was temporary, occurred during just 3 brief time periods each year, and did not negatively impact routine vaccine coverage of infants.30 Where loss to follow-up did occur, school transfers and family migration were noted to have been contributing factors.20,22,23 The complexity of logistics and coordination of vaccine delivery was amplified for school-based HPV vaccination programs, but careful planning at national level and close micro-planning with health authorities and schools at local levels were noted as important contributors to program success.22–24,28,30–32,39 The scheduling of vaccination dates to be convenient to schools, taking into consideration examination periods, holidays, and other busy times, and to complete the 3-dose series within a single school calendar year improved program implementation, as well as uptake and completion of vaccination.23,26,28,31,32,39 In places where HPV vaccine was offered for a few days at the scheduled time for each dose (sometimes referred to as “pulsed delivery”), staff tended to report easier logistics for implementation and follow-up than Ó 2014 Lippincott Williams & Wilkins
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Lessons Learned From HPV Vaccine Delivery
TABLE 1. HPV Vaccine Delivery Strategies and Uptake, LMICs, 2008–2011
Country (Reference)
Year
Bhutan22
2009
Bolivia22
2009 2010
Brazil26
2010–11
Cambodia22 2009 Cameroon22 2010 2009 Haiti22 India20 2009–10
Lesotho22 Nepal22,25
20,21
Peru
Rwanda39 South Africa24 Tanzania23
Uganda20
Vietnam20
Lead NGO/ MOH NGO NGO/ MOH Research hospital NGO/ MOH NGO NGO MOH
Strategy 9 schools
Eligible Female Population
No. Eligible or Target
Total Received 3 Doses, Administrative Report, N (%)
3-Dose Coverage, by Population-Based Survey
2721 (85)
NA
3739 (107) 27,597 (89)
NA NA
9–13 year-olds in schools
3200
57 schools 9–13 year-olds in schools 258 sites (schools + clinics) 9–13 year-olds at sites
3480 30,900
19 schools in research study Grades 6 and 7 in school
1574
1338 (85)
NA
1 government hospital 20 clinics 7 schools 279 schools + 399 clinics, campaign-style 258 schools + 273 clinics, routine delivery 47 sites (schools + clinics) 17 schools
2009–10
MOH
2009 20084
MOH NGO
20101 2007–083 2010–115 2011
NGO MOH MOH MOH
2011 2010–11
Provincial DOH NGO
2010–11
NGO
2008
MOH
67 schools in randomized trial 67 schools in randomized trial 195 schools + 41 clinics
2009
MOH
195 schools + 41 clinics
2008–09
MOH
2009
MOH
2008–09 2009–10 2008–09 2009–10
MOH MOH MOH MOH
222 schools + 28 integrated with health days 222 schools + 28 integrated with health days 38 schools 38 schools 34 clinics 34 clinics
24 sites (schools + clinics) 264 schools 163 clinics All schools in the country Outreach in the community 31 schools
clinics, child clinics, child
10–18 year-olds (employees’ children) 9–18 year-olds at clinics 9–13 year-olds in schools 10–14 year-olds at sites
2000
2029 (101)
NA
1600 3300 14,533
1033 (65) 2884 (87) 13,791 (95)
NA NA 77%–88%*
10–14 year-olds at sites
12,636
9864 (78)
68%–83%*
10–18 year-olds at sites 10–26 year-olds in schools 9–13 year-olds at sites Grade 5 in schools 11 year-olds at clinics Grade 6 12 year-olds out of school 9–12 year-olds in grades 4 and 5 Grade 6 at schools
40,000 1096
33,818 (84) 1089 (99)
NA NA
3000 13,677 10,075 94,141 4651 963
3164 (105) 10,963 (80) 6891 (68) 88,927 (95) 3180 (68) 938 (97)
NA 83% 53% NA NA NA
3352
2639 (79)
NA
12 year-olds at schools
2180
1572 (72)
NA
Grade 5 in schools and 10 year-olds out of school Grade 5 in schools and 10 year-olds out of school 10 year-olds at sites
3459
3038 (88)
91%
2835
2448 (86)
90%
2263
2388 (106)
53%
10 year-olds at sites
1923
1637 (85)
61%
Grade 6 at schools Grade 6 at schools 11 year-olds at clinics 11 year-olds at clinics
2412 1890 1507 1205
2012 1766 1399 1181
83% 96% 94% 99%
(83) (93) (93) (98)
*In India, coverage varied by geographic regions of urban, rural, or tribal areas.
in those places where vaccine was offered on a continuous basis.20,22–24,39 In addition, the routine (nonpulsed) delivery program implemented in India noted that more than 90% of all vaccines were taken up during the first month of offer, making regular follow-up visits less efficient.20 A few pilot programs delivered HPV vaccine primarily through local health centers, requiring girls and sometimes their parents to come to the facility to receive the necessary 3 doses. Such programs in Cameroon and Peru reported initial uptake of 83% and 76%, respectively, and 3-dose completion Ó 2014 Lippincott Williams & Wilkins
rates of 65% and 71%, respectively, demonstrating that both initial uptake and follow-up for completion of the 3-dose series had challenges (Table 1).20–22 Two donation programs used incentives with girls—t-shirt giveaways in Haiti and tracking bracelets in Nepal—to encourage completion of all 3 doses.22 In all school-based delivery schemes, except the randomized trial of delivery by age or grade in Tanzania, the nearest health facility to the school was also used as a place to catch girls who missed doses during school vaccination days or offer the vaccine to girls who were not enrolled or www.jaids.com |
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attending school.20,22,24 These additional opportunities, sometimes referred to as “mop up” vaccinations, were noted to be significant contributors to achieving high rates of overall coverage in South Africa.24 School-based programs in Bolivia (second year), India, Lesotho, Nepal (second year), Rwanda, Uganda, and Vietnam used additional community outreach to reach girls who were not enrolled or attending school (out-ofschool girls)20,22,39; the other school-based programs did not report any provision of vaccine to out-of-school girls. Peru reported that although there was no mechanism to track and find girls not attending school, a population-based survey conducted after vaccinations estimated that only about 0.3% were out of school among more than 8000 eligible girls in the region where vaccination occurred.21
Definition of Target Population Eligibility for HPV vaccine was based on schoolattending status, grade in school, and/or age. School-based programs used either age or grade as the primary determinant of eligibility (Table 1). In South Africa, both age and grade were used by selecting all girls in grades 4 and 5, as well as all girls aged 9–12 years in schools.24 All programs delivering vaccine through health facilities used age as the selection criterion for vaccination. Evaluation data from a few of the pilot programs noted that vaccine administration was logistically easier in schools when selecting girls based on their grade of enrollment, as age was often difficult to verify.20,24,31,39 There was no report from these initial programs of verifying the age of vaccinees at the time of each dose; instead, registers of eligible girls based on the program’s preset criteria were created before the vaccination program and then used to track girls’ receipt of each dose, in addition to vaccination cards (which only recorded age at the time of the first dose).24,31
Micro-planning and Coordination Close coordination and preparation for the exercise was noted to be a strong element in successful vaccine delivery, especially for programs that used schools as vaccination sites.22,24,30–32,39 Micro-planning, as done for routine immunization for infants, was observed to be critical in the demonstration projects in India, Peru, Uganda, and Vietnam. This micro-planning exercise also provided an opportunity to train health workers, providing them with a field guide for implementation, which reinforced learning, standardized delivery, and helped to maintain quality in the program’s administration.30–32 Involving the school sector in micro-planning facilitated coordination of the timing of vaccination days with the school schedule and helped map out which health facilities would cover which schools (PATH pilots only). In district- or region-wide programs, an individual health facility tended to cover only 2–4 nearby schools, thus easing the burden for delivery.31 In Rwanda, the creation of subcommittees for planning of vaccination, that included the education sector, was noted to be particularly helpful.39 In South Africa, coordination between the Departments of Health and Education at the district level included careful planning of vaccine storage at the local hospital, transportation of vaccine to schools, and vaccine administration by the school health teams.24
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Integration With Other Services The national introduction of HPV vaccine in Rwanda and the HPV vaccine demonstration programs by PATH were fully integrated into the routine program structures and operations of the national immunization programs within the participating districts.20,39 Unique to the program in 1 district of Uganda, HPV vaccine delivery was combined with semi-annual child health days, which distributed vitamin A, deworming, and supplemental vaccinations in the community,20,31 providing an example of service integration. Implementation costs from this program were half those incurred in the school-based program in Uganda.38 Integration with the provincial cervical cancer screening program was reported in the South African pilot, in which bags containing screening information were given to girls on the first vaccination dose.24 There are anecdotal reports that, in many areas, efforts to raise awareness about cervical cancer in preparation for vaccine programs also created demand for cervical screening services.
Training Training was critical to the preparation of staff to successfully implement the vaccination program, especially given the potentially sensitive cultural issues involved.22,30,31,39 Training curricula were customized for the audiences trained and their specific roles in the vaccination program—detailed for health workers, including the provision of a “field guide” to have as reference during program implementation, and less detailed for teachers. By and large, the methods included both participatory and didactic approaches and were supplemented by visual aids.30,31 Feedback from teachers during follow-up interviews suggested that teachers, in particular, appreciated the interactive training methods that were used. Having the opportunity to practice answering questions through role-play exercises and having materials especially designed for their communities made it easier for them to be effective resource people. Trainings lasted from one-half day to 3 days, depending on who was trained.28 Most school-based programs emphasized the critical role of training teachers to help inform students and parents and to assist in the logistics on days of vaccination in the classroom.22,30,31,39 Costing studies noted that training expenses accounted for 13%–43% of the proportion of startup financial costs of HPV vaccine delivery,38,40 and most programs reported that adequate financial resources are essential for effective training.22 A trade-off between cost of training and the magnitude and depth of the training was noted in Peru, particularly important when considering the question of replication and sustainability at a national scale.30
Community Outreach and Mobilization Issues Consent The use of written informed consent versus community consent was variable across vaccination programs. In general, programs implemented with a donation, such as from the Gardasil Access Program, required written informed consent from parents, and sometimes this form was several pages long.22,24 Demonstration programs in Peru, Uganda, and Ó 2014 Lippincott Williams & Wilkins
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Vietnam operated by the national EPI program, and the national program of Rwanda tended to use a community consenting, opt-out approach, as is done for other vaccines administered through routine government systems.20,39 Vietnam and Peru used a written consent the first year of their program, which raised suspicions among parents and was logistically difficult to manage; in the second year, this was modified to use either community consenting or a simple “parental authorization for services” form.21,28,30,32–34
Messages and Channels All pilot programs experienced a high level of acceptance, as indicated by the high levels of uptake of the vaccine in eligible populations, regardless of country.20,22,23,25,26,39 Several programs additionally evaluated motivators and factors that influenced parental decision making regarding vaccination.22,33–37,41,42 Protection against cervical cancer and expectation of a positive health benefit from vaccination were overwhelmingly the primary reasons for vaccination among parents surveyed in India, Peru, Tanzania, Uganda, and Vietnam.20,41 These were also motivators for girls accepting vaccine, as indicated by surveys with girls from Uganda, Vietnam, and Tanzania.35,37,41 Directly addressing parental concerns, identified before vaccination,15,16 with the communication activities and materials during the vaccination exercise was also emphasized as a key reason for high levels of acceptance of HPV vaccine in the community.22,33–36,41,42 Clear concise messages in locally understood terms were important.22,28,35,42 In Peru and Vietnam, it was particularly important to give parents adequate time to make a decision, as many parents did not immediately consent at first offer.33,34 Results from Tanzania suggested that this approach might have been beneficial, as the majority of parents and girls interviewed who were not vaccinated indicated they would agree to receive HPV vaccine if it were offered again.41 Research from Uganda and Vietnam suggested that the person a parent consulted with or received information from was more important than the specific education materials they received.36 All pilot programs reported that parents had concerns about vaccine safety and impact on future fertility, and that these concerns should be addressed in any communication activity or materials used before HPV vaccination.20,33–36,41,42 The communication modalities used to raise awareness and disseminate information for vaccine decision making were varied, as was the time in which these activities were conducted. Leaflets and posters were a common feature, as were radio announcements and other broadcasts in the community of vaccination dates and key messages.28,36,41,42 Meetings with parents at schools, health centers, or in the community were also conducted.28 Most programs conducted mobilization and sensitization activities before each dose of vaccine with the most intense activities occurring before dose 1. Announcements in church and use of key trusted persons, like religious or community leaders, to disseminate information were noted to be helpful.28,31,36 As with training costs, program implementation costs for social mobilization were significant, comprising nearly one-half of all start-up costs Ó 2014 Lippincott Williams & Wilkins
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in Uganda, two-thirds of the start-up costs in Peru, and fully three-quarters of the start-up costs in Vietnam.38
Endorsement and Support Significant involvement by and support from the national government were noted to be critical factors for program success and community uptake.20,30–32,34,39 The endorsement by government assured the credibility of the program, as most parents respected and trusted the work of the national immunization program as a whole.31,39 Having visible government endorsement through high-profile launches that sometimes even included the First Lady of the country were also reported to be of positive benefit.31 Vaccination programs that implemented immunizations through the staff who were routinely administering infant vaccines tended to work better, with fewer logistical complications, than those that hired separate staff or otherwise administered vaccinations outside the regular government EPI program.22 As noted earlier, other local leaders and persons of influence helped bring credibility to the vaccination program and influenced a broader positive environment for acceptability.22,31,36,39 Understanding who these persons may be and sensitizing them in advance of program implementation helped prepare them to provide key messages to the community. As a part of the local leader endorsement and support, education officials, teachers, school headmasters, and others affiliated with the education sector were helpful in creating an enabling environment to support the vaccination program, both before vaccinations and during immunization sessions.22,31–34,37,41,42 Crisis communication plans and managing rumors were important components of nearly all vaccination pilots. Programs with the strong involvement of the government gave particular attention to this issue.28,31,41 Having defined roles and clear messages enabled a rapid and effective response by respected and trusted officials when needed.
Timing of Mobilization Efforts Although not specifically evaluated in the published literature, descriptions of program implementation for HPV vaccinations seem to suggest different time frames for mobilization and sensitization from national level down to the local level. These are summarized in Table 2. In general, it is important to ensure far in advance, 6–9 months, that all the appropriate national level stakeholders are fully briefed and sensitized to build the foundation of strong government endorsement before vaccination planning. After that, a cascade of mobilization and sensitization occurs at district level
TABLE 2. Key Stakeholder Groups and Timing of Sensitization and Mobilization for HPV Vaccine Delivery Group National and local officials National and regional CSO leaders Local influential groups Heads of individual schools Parents and girls
How Far Ahead to Engage (mo) 6–9 3–6 3 3 1
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(3–6 months before), local level trainings, including teachers and schools (2–3 months before), and community sensitizations and awareness-raising activities at least 4 weeks before the administration of the first dose.28
DISCUSSION HPV vaccine delivery has several characteristics that make the lessons derived from it particularly relevant to interventions to prevent HIV infection among adolescents, and perhaps to a lesser extent to serve the needs of the subgroup of those already infected. Few other health interventions address young adolescents—a group that has been relatively neglected in HIV prevention programs, but among whom prevention messages could pay off the most. Like HIV, HPV vaccine has obvious associations with sensitive sexual issues and also deals with consequences that may be perceived as distant in the future, although AIDS is much closer in time than cervical cancer and more visible. Because HPV vaccine is new and has attracted a lot of attention, we are fortunate to have some intensive evaluations that have yielded lessons across many different geographic, social, religious, linguistic, and cultural settings.
Operational Lessons Relevant to HIV Services The relevance of operational lessons drawn from the HPV vaccine experience (which might also fit the category called “program enablers” in the UNAIDS investment framework43) depends in part on the nature of the intervention. To the extent that HIV interventions are medical and outpatient (such as a vaccine or other prophylactic medication that requires health worker administration), the evidence about schools as a good venue is encouraging. Although enrollment rates in developing countries vary, the heavy emphasis on schoolbased delivery for HPV vaccine reflects recent transformations: attendance rates for girls in primary schools have been increasing rapidly,14 as countries invest more in economic development and expand access to universal primary education. HPV vaccine programs show that schools can be an effective place to reach young adolescents, including with brief interventions that require follow-up once or twice during the school year. We did not find the problems identified by Plummer et al44 in a qualitative study in Tanzania—authoritarian and abusive teachers, high rates of school absenteeism and dropouts—to be major obstacles, but perhaps that was because of the episodic nature of the demands on teachers. School delivery of health services requires careful planning and coordination with education officials at all levels, ensuring that teachers are engaged and prepared for the roles expected of them, and fitting the timing of interventions to the school calendar of holidays and examinations; the same lessons will certainly apply to HIV interventions. Time and cost implications of school delivery also require careful consideration. For equity reasons, school programs may have to be accompanied by initiatives for non–school-going adolescents, such as outreach or clinicbased service delivery. Defining the target population is important for any intervention, both for implementation and for subsequent
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monitoring and evaluation. If the intervention is age sensitive (as it is for HPV vaccine), then it will be critical to determine the extent to which approximate age is known or can be determined and documented. Although some countries have made progress with birth registration and identity documents, it seems that there are still many younger generations of schoolgoers who do not know their ages. In sub-Saharan Africa, only 41% of births were registered in the 2006–2011 period.45 With classrooms still encompassing a wide range of student ages, along with the natural variation in social maturing, it is a challenge to provide age-appropriate information on topics such as sexuality and safe sexual practices, and an operational challenge to reach across different classrooms to group children of similar ages. This might be more critical for HIV-related information than it was for HPV vaccination, which was less dependent on social maturity levels in shaping its messages. District-level micro-planning has been particularly well developed for immunization activities,46 but the techniques are useful for other health activities as well and were particularly appropriate for the pulsed nature of HPV vaccines. The coordination between the health and education sectors that was so critical for school-based HPV vaccine delivery would likely be important for HIV activities that might draw not only on multiple units within health ministries but also other ministries like youth, education, labor, and finance, as well as nongovernmental or community-based organizations that reach adolescents. It was apparent from the experience with Child Health Days in Uganda that combining HPV vaccine delivery with other interventions that were being done in the community was a cost-effective approach.31,38 As long as the same health staff were involved, there was at least overlap (if not an exact match) of the target groups, and the length of time needed for the new intervention did not significantly impact the other activities, then integration could be very beneficial. Such combinations save time on planning and travel, save transport costs, and share costs of social mobilization.38 The same could apply to HIV interventions, as long as the frequency of the HIV intervention matches the timing of the intervention it is combined with and care is taken to ensure that no stigma will accrue to the other interventions from the HIV message. The low level of knowledge on cervical cancer and HPV found in baseline formative research on the part of health workers and teachers,15,16,47–49 let alone community members, prompted governments to provide detailed training to them to ensure that they would be able to answer questions from parents, girls, and other community members.30,31 Training adults to relate to the concerns and language of adolescents is something that HIV/AIDS programs and pregnancy prevention programs have already encountered.50,51 Using participatory methods to train teachers may also help model for them how to use such methods with adolescents who are transitioning from passive, rote learners to active, questioning learners.
Community Outreach and Mobilization Lessons Community outreach and mobilization lessons from the HPV vaccine experience are highly relevant to HIV services, Ó 2014 Lippincott Williams & Wilkins
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especially preventive services where stigma and denial may be at play, such as voluntary counseling and HIV testing. This may be a particular issue when deciding what kind of consent for services is needed for adolescents. As is the case with family planning for older adolescents, there are issues of stigma, privacy, and autonomy for HIV programs. These have been less evident in the experience with HPV vaccines because they have involved mainly young prepubescent adolescents aged 10–12 years. Local customs around consent for other interventions will set the tone for HIV interventions, as they did for HPV vaccine. One of the most important lessons was that if the intervention is singled out for special requirements, it will raise suspicions and concern that the government has reservations or the intervention is experimental.30 The process of community mobilization and the methods used for HPV vaccinations has relevance for the delivery of HIV services. Preparing and using materials for parents that directly answer the questions they have, often generated through previous formative research, helped to focus key messages for informed decision making. One of these messages was that the intervention, in this case HPV vaccination, was endorsed by the government. Using appropriate channels where parents receive information, often from a trusted source like a health worker or teacher, is even more important where young adolescents are involved and may enhance the effectiveness of existing community awareness activities related to HIV prevention, often designed for older adolescents rather than their parents.52 There is no real parallel in HPV vaccination programs for the level of stigma that might attach to adolescent disclosure of positive HIV status, but the same underlying principles of building broad community support, including addressing parental concerns, should apply.
Limitations Although there are now a diverse set of countries for which lessons from HPV vaccinations for young adolescent girls have been summarized, our synthesis of these is constrained by the limited amount of published literature. Most of the articles reviewed were generated from 1 large 4-country project. However, similar results were found from other country experiences, suggesting common themes are emerging. The literature is also deficient in the number of rigorous evaluations conducted from either pilots or national scale-up of HPV vaccinations in LMICs, although more than 30 countries and territories have such experience. The general target of HPV vaccination programs in low-resource settings has been young adolescents, and therefore, the application of lessons working with this population may be less relevant for HIV interventions directed toward older adolescents.
CONCLUSIONS Despite the huge amount of attention that has been devoted to prevention and treatment services related to HIV/ AIDS, there are still many unanswered questions related to the special needs of adolescents, and particularly young Ó 2014 Lippincott Williams & Wilkins
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adolescents.53 The delivery of HPV vaccines, one of the few health interventions specifically targeted at young adolescents, provides an opportunity to see in action how a service with some similar characteristics has worked in low-resource settings. Some of the HPV vaccine lessons are common sense (but have not been well documented before), whereas others have surprised skeptics who predicted bigger problems with acceptability and logistics than were actually encountered. 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 most significant lessons that are relevant for HIV interventions, but many of the smaller details were also important, and applying or adapting them to adolescent HIV services could accelerate effective program design and enhance success.
ACKNOWLEDGMENTS The authors thank Susan Kasedde for helpful comments on the article, Jane Goett at PATH and Celina Hanson at GAVI for their assistance with the literature review, and David Oxley at PATH for administrative support. REFERENCES 1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917. 2. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356: 1915–1927. 3. Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374: 301–314. 4. World Health Organization. Human papillomavirus vaccines: WHO position paper. Wkly Epidemiol Rec. 2009;15:118–131. 5. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 viruslike particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95: 1459–1466. 6. Roteli-Martins CM, Naud P, De Borba P, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012;8:390–397. 7. Brotherton JM, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet. 2011;377:2085–2092. 8. Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11:227. 9. Rana MM, Huhtala H, Apter D, et al. Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: cancer registry-based follow-up. Int J Cancer. 2013;132:2833–2838. 10. Kane MA, Sherris J, Coursaget P, et al. Chapter 15: HPV vaccine use in the developing world. Vaccine. 2006;24:S3/132–139. 11. Sherris J, Friedman A, Wittet S, et al. Chapter 25: education, training, and communication for HPV vaccines. Vaccine. 2006;24:S3/210–218. 12. World Health Organization and United Nations Population Fund. Preparing for the Introduction of HPV Vaccines: Policy and Program Guidance for Countries. Geneva, Switzerland: WHO; 2006. 13. Principi N, Esposito S. Adolescents and vaccines in the western world. Vaccine. 2013;31:5366–5374.
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14. Global Education Digest 2012-Interactive Data Tool. UNESCO Institute for Statistics. Available at: http://www.uis.unesco.org/Education/Pages/ ged-2012-visualization.aspx. Accessed January 22, 2014. 15. Katahoire A, Jitta J, Kivumbi G, et al. An assessment of the readiness for introduction of the HPV vaccine in Uganda. Afr J Reprod Health. 2008; 12:159–172. 16. Jacob M, Mawar N, Menezes L, et al. Assessing the environment for introduction of human papillomavirus vaccine in India. The Open Vaccin J. 2010;3:96–107. 17. United Nations Population Fund (UNFPA). State of World Population 2013: Motherhood in Childhood, Facing the Challenge of Adolescent Pregnancy. New York, NY: UNFPA; 2013. 18. Bearinger LH, Sieving RE, Ferguson J, et al. Global perspectives on the sexual and reproductive health of adolescents: patterns, prevention, and potential. Lancet. 2007;369:1220–1231. 19. Tylee A, Haller D, Graham T, et al. Youth-friendly primary-care services: how are we doing and what more needs to be done? Lancet. 2007; 369:1565–1573. 20. LaMontagne DS, Barge S, Le NT, et al. Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middleincome countries. Bull World Health Organ. 2011;89:821–830B. 21. Penny M, Bartolini R. Evaluation of demonstration project 2010: health facility based immunization of 10 year old girls with HPV vaccine; part I: how does offering HPV vaccine in the health facility to 10 year old girls compare with a school based approach? Technical research report submitted to PATH; 2011. 22. Ladner J, Besson MH, Hampshire R, et al. Assessment of eight HPV vaccination programs implemented in lowest income countries. BMC Public Health. 2012;12:370. 23. Watson-Jones D, Baisley K, Ponsiano R, et al. Human papillomavirus vaccination in Tanzanian schoolgirls: cluster-randomized trial comparing 2 vaccine-delivery strategies. J Infect Dis. 2012;206:678–686. 24. Moodley I, Tathiah N, Mubaiwa V, et al. High uptake of Gardasil vaccine among 9-12-year-old schoolgirls participating in an HPV vaccination demonstration project in KwaZulu-Natal, South Africa. S Afr Med J. 2013;103:313–317. 25. Singh Y, Shah A, Singh M, et al. Human papilloma virus vaccination in Nepal: an initial experience. Asian Pac J Cancer Prev. 2010;11:615–617. 26. Fregnani JH, Carvalho AL, Eluf-Neto J, et al. A school-based human papillomavirus vaccination program in barretos, Brazil: final results of a demonstrative study. PLoS One. 2013;8:e62647. 27. Axios International. The Gardasil Access Program. Available at: http://www. gardasilaccessprogram.org/section/177. Accessed November 25, 2013. 28. PATH. Implementing HPV Vaccination Programs: Practical Experience From PATH. Seattle, WA: PATH; 2011. Cervical Cancer Prevention: Practical Experience Series. 29. Progress for children: A report card on adolescents. United Nations Children’s Fund, Number 10, April 2012. Available at: http://www. unicef.org/media/files/PFC2012_A_report_card_on_adolescents.pdf. Accessed November 25, 2013. 30. Penny M, Bartolini R, Mosqueira NR, et al. Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru. Vaccine. 2011;29:5022–5030. 31. Mugisha E, LaMontagne DS, Katahoire AR, et al. Feasibility of delivering HPV vaccine to girls aged 10 to 15 years in Uganda. Afr Health Sci. Provisional acceptance, August 26, 2013. In press. 32. LaMontagne DS, Nghi NQ, Nga LT, et al. Feasibility of HPV vaccination in Vietnam: evidence from a government-implemented demonstration program. BMC Public Health. 2013. 33. Bartolini RM, Winkler JL, Penny ME, et al. Parental acceptance of HPV vaccine in Peru: a decision framework. PLoS One. 2012;7:e48017. 34. Cover JK, Nghi NQ, LaMontagne DS, et al. Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination. BMC Public Health. 2012;12:629.
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35. Paul P, LaMontagne DS, Nga LT. Knowledge of cervical cancer and HPV vaccine post-vaccination among mothers and daughters in Vietnam. Asian Pac J Cancer Prev. 2012;13:2587–2592. 36. Galagan SR, Paul P, Menezes L, et al. Influences on parental acceptance of HPV vaccination in demonstration projects in Uganda and Vietnam. Vaccine. 2013;31:3072–3078. 37. Katahoire A, Murokora D, Arube-Wani J, et al. Acceptability of HPV vaccine among young adolescent girls in Uganda: young people’s perspectives count. Int J Child Adol Health. 2013;6:211–220. 38. Levin CE, Minh HV, Odaga J, et al. Incremental costs of strategies to deliver human papillomavirus vaccine to young adolescent girls in Peru, Uganda and Vietnam. Bull World Health Organ. 2013;91:585–592. 39. Binagwaho A, Wagner CM, Gatera M, et al. Achieving high coverage in Rwanda’s national human papillomavirus vaccination programme. Bull World Health Organ. 2012;90:623–628. 40. Quentin W, Terris-Prestholt F, Changalucha J, et al. Costs of delivering human papillomavirus vaccination to school girls in Mwanza region, Tanzania. BMC Med. 2012;10:137. 41. Watson-Jones D, Tomlin K, Remes P, et al. Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in Tanzania: a case control study. PLoS One. 2012;7:e45231. 42. Wamai RG, Ayissi CA, Oduwo GO, et al. Assessing the effectiveness of a community-based sensitization strategy in creating awareness about HPV, cervical cancer and HPV vaccine among parents in North West Cameroon. J Community Health. 2012;37:917–926. 43. UNAIDS. Investing for Results. Results for People. A People-Centered Investment Tool Towards Ending AIDS. Geneva, Switzerland: UNAIDS; 2012. Available at: http://www.unaids.org/en/media/unaids/contentassets/ documents/unaidspublication/2012/JC2359_investing-for-results_en.pdf. Accessed November 25, 2013. 44. Plummer ML, Wight D, Wamoyi J, et al. Are schools a good setting for adolescent sexual health promotion in rural Africa? A qualitative assessment from Tanzania. Health Educ Res. 2007;22:483–499. 45. UNICEF. State of the World’s Children. New York, NY: UNICEF; 2013. Available at: http://www.unicef.org/sowc2013/. Accessed November 15, 2013. 46. World Health Organization and UNICEF. Microplanning for Immunization Service Delivery Using the Reaching Every District (RED) Strategy. Geneva, Switzerland: World Health Organization; 2009. Available at: http://www.who.int/immunization/sage/9_Final_RED_280909.pdf. Accessed November 17, 2013. 47. Bingham A, Drake JK, LaMontagne DS. Sociocultural issues in the introduction of human papillomavirus vaccines in low-resource settings. Arch Pediatr Adolesc Med. 2009;163:455–461. 48. Bartolini RM, Drake JK, Creed-Kanashiro HM, et al. Formative research to shape HPV vaccine introduction strategies in Peru (Investigación formativa para diseñar estrategias para la introducción de la vacuna contra el VPH en el Perú). Salud Pública de Méx. 2010;52:226–233. 49. Nghi NQ, LaMontagne DS, Bingham A, et al. Human papillomavirus vaccine introduction in Vietnam: formative research findings. Sex Health. 2010;7:262–270. 50. WHO. Making Health Services Adolescent Friendly: Developing National Quality Standards for Adolescent Friendly Health Services. Geneva, Switzerland: WHO; 2012. 51. Kirby DB, Laris BA, Rolleri LA. Sex and HIV education programs: their impact on sexual behaviors of young people throughout the world. Adolesc Health. 2007;40:206–217. 52. Napierala Mavedzenge SM, Doyle AM, Ross DA. HIV prevention in young people in sub-Saharan Africa: a systematic review. J Adolesc Health. 2011;49:568–586. 53. WHO. Review of the Social Determinants and the Health Divide in the WHO European Region: Final Report. Copenhagen, Denmark: WHO; 2013. Available at: http://www.euro.who.int/__data/assets/pdf_file/0006/ 215196/Review-of-social-determinants-and-the-health-divide-in-the-WHOEuropean-Region-final-report-Eng.pdf. Accessed January 21, 2014.
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