Human Papillomavirus Vaccination Coverage Among School Girls in a Demonstration Project — Botswana, 2013

Mmakgomo Mimi Raesima, MD1; Sara E. Forhan, MD2; Andrew C. Voetsch, PhD2; Shannon Hewitt3; Susan Hariri, PhD4; Susan A. Wang, MD5; Andrew R. Pelletier, MD2; Mpho Letebele, MD2; Tlhomamo Pheto1; Doreen Ramogola-Masire, MD6,7; Shenaaz El-Halabi, MPH1

Cervical cancer, caused by human papillomavirus (HPV), is the leading cause of cancer mortality among women in Botswana (1). Three vaccines prevent infection with HPV types responsible for the majority of cervical cancer worldwide. Two of these vaccines also protect against types that cause anogenital warts. Two vaccines are currently prequalified by the World Health Organization (WHO); these were >90% efficacious in preventing precancerous lesions caused by HPV types 16 and 18 (the cause of 70% of cervical cancers) in clinical trials studying women who received the recommended 3-dose series before exposure to targeted HPV types. WHO recommends targeting HPV vaccination to girls aged 9–13, before initiation of sexual activity and thus HPV exposure (2). This report summarizes HPV vaccination coverage among girls aged ≥9 years enrolled in grades 4–6 in 23 primary schools in Molepolole, Botswana, during a 2013 HPV vaccination demonstration project conducted by the Botswana Ministry of Health (MOH). Of the 2,488 eligible school girls, 83% received the first dose and 79% completed the 3-dose HPV vaccination series. Drop out between first and third dose was 5%. No serious adverse events were reported. Given the successful pilot, the project was expanded to immunize approximately 6,000 girls in 2014, followed by national rollout of the HPV vaccine in 2015.

Botswana is an upper middle income country with a population of 2 million in southern Africa. Approximately 22,000 females are born annually. Human immunodeficiency virus (HIV) prevalence among women aged 15–49 years is 28%.* Cervical cancer, the fourth most common cancer worldwide (3), is the most common cancer among women aged 15–44 years and the leading cause of cancer mortality among women in Botswana, reflecting the 4–5 times increased risk for cervical cancer among HIV-infected women (3). Primary prevention of cervical cancer via HPV vaccination might be particularly beneficial to Botswana, given the country's challenges with both HIV infection and cervical cancer. However, establishing a sustainable program to deliver HPV vaccine to a population not previously targeted for immunizations can be challenging in resource-limited countries.

In 2012, the Botswana MOH initiated its National Cervical Cancer Prevention Program Comprehensive Strategy (2012–2016). The same year, the Pink Ribbon Red Ribbon (PRRR) initiative, a public-private partnership for breast and cervical cancer prevention and treatment, was implemented to expand cervical cancer screening and treatment with a focus on HPV-related disease. With PRRR and other donor support, the Botswana MOH decided to conduct a grade-based HPV vaccination demonstration project in primary schools. The project was completed during the 2013 school year (January–December) in Molepolole, a town with a population of 63,000 located 31 miles (50 kilometers) from the national capital. The objectives were to evaluate HPV vaccine implementation among age-eligible girls enrolled in school and to improve planning for possible expansion of HPV vaccine activities.

A multidisciplinary team, with representatives from the Botswana MOH, including Expanded Program on Immunization, Ministry of Education, WHO, nongovernmental organizations, and other key stakeholders, developed the project protocol, educational materials, a parental consent form, and data-gathering tools. The Botswana MOH determined the project to be public health practice. Multiple educational meetings for community stakeholders, sensitization meetings for parents and educators, and training sessions for local public health providers participating in the project were held before implementation. All girls aged ≥9 years attending grades 4–6 at any of Molepolole's 17 public primary schools, five private primary schools, or one school for special needs students, and who had written parental consent, were eligible for vaccination. Participating schools provided enrollment lists of female students. The quadrivalent HPV vaccine, Gardasil (Merck and Co.), was administered in schools by public health workers in March, May (approximately 2 months after the first dose), and early October 2013 (approximately 6 months after the first dose). Immunization teams visited each school twice during each of the three vaccination campaign rounds. Girls who missed a dose at school could receive it at Scottish Livingston Hospital in Molepolole. Vaccination data on each girl were collected on paper-based records and transferred to a spreadsheet. To identify the number of girls who received HPV vaccination during March–December 2013, staff reviewed the line lists of girls by school, which contained birthdate, grade, documentation of parental consent, and HPV vaccination date.

There were 2,742 girls registered in grades 4–6 in the 23 participating schools (median enrollment = 135 girls; range = 12–227 girls). Of the 2,590 (94%) girls with a recorded date of birth, 2,488 (96%) were aged ≥9 years on the first day of school vaccination in March 2013. Among these girls, 83% (n = 2,075) received the first dose, 82% (n = 2,049) received 2 doses, and 79% (n = 1,967) completed the 3-dose series (Table). Overall vaccination completion among girls who received the first dose was 95%. Approximately one fifth (431/2488) of girls with known date of birth were without documented parental consent, 88 of whom received vaccination. The proportion of school girls vaccinated increased with increasing age (Cochran-Armitage trend test p<0.001) and was higher among girls who attended public school compared with those who attended private school (p<0.001). Passive surveillance for adverse events (following girls for 30 days postimmunization) was designed for this campaign. No serious adverse events were reported.

Discussion

HPV vaccines are safe and highly efficacious (4); postlicensure monitoring data from countries with high vaccination coverage indicate population-level impact against early cervical disease caused by targeted HPV types, further supporting these results (5). The vaccines' potential impact is likely to be greatest in countries with less established cervical cancer screening programs and high disease levels, such as Botswana; however, delivering a multidose vaccine to adolescent girls is challenging and has impeded large scale introduction in low-resource countries.

The 79% 3-dose vaccination coverage achieved in this project is comparable to that attained in an HPV vaccination project conducted in the Mwanza Region, Tanzania (76.1%), but lower than the vaccination coverage in school-based demonstration projects in KwaZulu Natal province, South Africa (97.8%) (6,7). Approximately all doses were administered on time and at schools. Similar to the Tanzania demonstration project, the vaccination rate was higher in public than in private schools (6).

The findings in this report are subject to limitations. Out-of-school preadolescent girls were not represented in the estimated vaccination coverage; thus vaccination coverage is likely overestimated for the general population of girls aged 9–13 years. WHO recommends use of population-based data to identify all eligible girls in the population by year of age.† In this project, the number of out-of-school girls in the Molepolole catchment area was not available. However, an estimated 15% of primary school-aged girls were out-of-school in Botswana in 2009 (8). Vaccination coverage might have been underestimated because of incomplete documentation of doses administered at Scottish Livingston Hospital, or because the analysis excluded girls without recorded birthdates who were immunized. The scalability and sustainability of the HPV vaccination strategy used in this demonstration project were not assessed.

Programmatic challenges and expense of the 3-dose HPV vaccination series led to global interest in a 2-dose HPV vaccine schedule (0, 6–12 months). By using data from noninferiority immunogenicity trials and postlicensure studies of both vaccines, in April 2014, WHO recommended a 2-dose schedule for immunization of immunocompetent girls aged 9–14 years for either vaccine at 0, 6- or 0, 12-month intervals (2). The full 3-dose series remains recommended for girls aged ≥15 years, for those who are immunocompromised, or whenever interval between the first 2 doses is <6 months.

Demonstration projects are valuable to identify and address challenges, build necessary partnerships across government agencies and with other stakeholders, and gauge political support before implementing a national vaccination program. Although Botswana's demonstration project successfully achieved high vaccination coverage among girls enrolled in school, problems with implementation occurred. At campaign initiation, certain grade 4 girls were aged <9 years, precluding complete vaccination of grade 4 girls through this project. Required signed parental consent, a nonstandard practice for Botswana's immunization program, likely created confusion that resulted in 1) vaccination of certain girls who lacked signed consents, and 2) lower vaccination rates, despite robust precampaign community sensitization efforts. On the basis of the 2013 challenges, Botswana's 2014 HPV vaccination project was modified to target grades 5–7 and replaced formal written consent with an implied consent process (9).

The national HPV vaccine rollout in 2015 employed a 2-dose vaccination schedule. Recent post hoc analysis of data from two large vaccine trials reported that women aged 15–25 years who received a single dose of HPV vaccine were protected against HPV types 16 and 18 for 4 years after vaccination (10). In Botswana, concerns still being discussed include how best to provide vaccinations to out-of-school girls; the best venue for delivering vaccine (school versus health care facility); and how to provide a third dose to girls who are HIV-infected (HIV prevalence among girls aged 10–14 years is 4.4% in Botswana), aged ≥15 years, or received the first 2 doses <6 months apart.

Acknowledgments

Botswana Ministry of Health HPV Immunization Working Group, Gaborone, Botswana; public health workers in Molepolole, Botswana.

1Botswana Ministry of Health; 2Division of Global HIV/AIDS, Center for Global Health, CDC; 3United States Peace Corps; 4Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC; 5Global Immunization Division, Center for Global Health, CDC; 6Botswana-University of Pennsylvania Partnership; 7Department of Medicine, University of Botswana.

Corresponding author: Sara Forhan, ggt1@cdc.gov, 404-639-0374.

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