Interventions to Improve HPV Vaccine Uptake: A Systematic Review

"Multiple interventions to address poor vaccination rates have increased knowledge of HPV-related diseases and the HPVV....Although vaccination intent was increased, it was neither sustained nor translated into vaccination behavior. Furthermore, there has been speculation that parents from different ethnic and socioeconomic groups may face different barriers to vaccination and thus require different intervention strategies..."

This study sought to understand and address the fact that the human papillomavirus (HPV) vaccine (HPVV) is a "safe, effective cancer prevention method" that is underutilised in the United States (US). Despite recommendations by the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) for its use for girls and boys aged 9 to 26, as well as increased understanding of barriers to vaccination, rates in that country remain low, while globally, developed and developing nations have achieved high rates of vaccination.

To gain insight from global efforts, researchers conducted a systematic review of the literature for national and international initiatives to increase HPV vaccination. Only articles including postintervention HPV vaccination rates were included. They used a standardised protocol to search for articles published between January 1 2006 and April 30 2015 in 3 electronic databases: PubMed, Scopus, and Embase. Results were reported according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Fifty-one articles met eligibility criteria: 2 informational interventions, 18 behavioural interventions, and 31 environmental interventions. There was considerable variation in the number of participants reached by an intervention. In general, environmental interventions had the largest scope, consistently reaching >100,000 adolescents, whereas behavioural interventions reached as few as 37 adolescents.

The overall finding is that environmental approaches consistently reached the greatest number of participants and achieved the highest vaccination rates. "Environmental interventions, particularly school-based VP, had two major advantages that contributed to their success: increased access to the HPVV and ability to reach a large, diverse population, regardless of individual access to health care." Furthermore, "[t]he remarkable success internationally of government-initiated HPVV programs should be used to inform and guide US policy. When population-based vaccination strategies are not feasible, we support multipronged interventions that target both the provider and the patient."

Specifically, with regard to the types of interventions:

• Informational Interventions (n = 2): Example - An intervention in the US reached out to low-income parents and provided HPVV education, resulting in higher rates of series completion compared with preintervention (58% vs 42%). A community-wide media information campaign in the US reaching out to adolescent boys resulted in higher rates of HPV vaccination in the exposed community during the media campaign compared with the control community (hazard ratio 1.34). There was no significant difference between case and control groups in the postintervention period. General finding for this category of intervention: "Informational interventions using both individualized and community-wide education campaigns improved vaccination uptake during the active intervention period. However, there was no evidence to suggest the effect was sustained, indicating that this is not a sufficient modality when used alone."
• Behavioural Interventions: (i) Patient Targeted Decision Support (n = 5) - Example: students at a German school randomised to receive an evidence-based "balanced" leaflet versus those randomised to a sensationalist "unbalanced" leaflet had improved understanding of the HPVV but no difference in vaccination behaviour. (ii) Patient-Targeted Reminder Interventions (n = 7) - Example: A US study found that reminder letters scheduled quarterly were effective to enhance HPV vaccine series completion among those who initiated the vaccine. However, a large gap in series completion remained despite the intervention. (iii) Provider-Targeted Interventions (n = 4) - Example: An intervention including electronic medical record prompts of patients overdue for the HPVV did not increase vaccination rates during the intervention period. Inaccurate vaccine tracking resulting in missed vaccination opportunities were cited as potential barriers to intervention success. (iv) Patient- and Provider-Targeted Interventions (n = 2) - Example: An approach that included patient-focused education and telephone reminders with physician alerts and a script to address parents concerns resulted in 62.5% completion, representing a nearly 10-fold increase compared with the control group. Authors commented that implementation of the programme was simple, and parents welcomed the information. General finding for this category: "Behavioral interventions demonstrated a range of effectiveness, required significant effort, and had inconsistent outcomes. There was a consistent lack of reporting implementation barriers common to all decision support interventions, information that would be useful to guide future interventions."
• Environmental Interventions: (i) Small Policy (n = 12) - Examples: School-based vaccination programmes (VPs) in Brazil and South Africa included education campaigns and free vaccination, demonstrating uptake rates of 85% (completion) and 58.6% (at least 1 dose), respectively. Similar implementation challenges faced both programmes: parents refusing to participate (up to 41%) or not attending educational classes. A programme in the Netherlands was an exception to the widespread success of national school-based VPs, reporting HPVV initiation rates at 49.9%. The authors questioned the quality of the education campaign and speculated that distrust of the HPVV among the local scientific community may have contributed to poor vaccination rates. An intervention in Peru including cervical cancer screening of an older relative and free HPVV resulted in high rates of series completion (65%), despite recruitment challenges and limited HPV knowledge. (ii) Big Policy, National Government Involvement (n = 12) - Examples: Australia was the first country to institute a national HPV programme and observed high completion rates at 1 and 5 years (77% and 70%, respectively). In addition to a school-based VP for 11- and 12-year-olds with catch-up for older students, there was early recognition of low rates of school attendance among indigenous populations, and efforts were made to increase HPVV availability in novel locations. Other challenges included HPVV safety concerns, obtaining parental consent, variable familiarity with school-based VPs, and variation in uptake across territories. (iii) Big Policy, Local Government Involvement (n = 7) - Example: A clinic-based intervention in a Japanese municipality included an official announcement by the mayor. High completion rates were observed among 14- and 15-year-olds (81%), whereas 11- and 12-year-olds had vaccination completion rates similar to the US (32.4%).

Environmental interventions, particularly school-based VP, had 2 major advantages that contributed to their success: increased access to the HPVV and ability to reach a large, diverse population, regardless of individual access to health care. Important themes emerged from descriptions of international school-based VP, which were widely accepted and welcomed by key stakeholders, including school personnel and parents. The success of environmental interventions in developing countries through school- and clinic-based vaccination programmes illustrated that high vaccination coverage is not limited to high-income populations. "[C]ommunity support is vital for school-based VP to be successful. This may in part explain the low participation in school-based VP in the United States compared with those abroad."

Several articles commented on barriers specific to public perception of the HPVV: lack of HPV knowledge, negative media surrounding the HPVV, and HPVV safety concerns. Although not specific to intervention implementation, authors postulated these challenges likely compromised overall success of the intervention. On the subject of barriers, one theme that emerged was that provider-targeted interventions appeared to be most successful for HPVV series initiation, while patient-targeted interventions appeared to be most successful for series completion. This indicates that providers pose a more significant barrier to vaccine series initiation, while patient or family barriers are a greater hindrance to series completion. On the whole, factors associated with HPV vaccine uptake were increased vaccine availability, decreased financial barriers, and interventions seeking to reach both providers and patients.

In terms of directions for future research, "[o]ne consistent deficiency in nearly all studies was the lack of data on race/ethnicity and socioeconomic status reporting, making it difficult to elucidate trends to support the theory that participants from different backgrounds respond preferentially to certain interventions. Given the significant disparity in outcomes of HPV related diseases, it is imperative we develop a better understanding of the relationship between demographics and vaccination behavior. As demonstrated in this review, environmental interventions targeting underserved populations can be successful and should be employed to protect the most vulnerable adolescents."