Evidence supporting the initiation of HPV vaccination starting at age 9: Collection overview

Introduction

HPV vaccination has been shown in both clinical trials and longitudinal population studies to reduce infection, precancer, and cancer.^1–3 Its safety has been demonstrated through clinical trials, numerous research studies, and continuous safety monitoring in more than 180 countries for nearly two decades.^4,5 The HPV vaccine has been recommended for females in the U.S. since 2006, with routine vaccination for all adolescents since 2012.⁶ Yet, despite being part of routine adolescent vaccinations for more than a decade, the long track record for safety, and strong evidence for cancer prevention, fewer than one-half of US adolescents complete the HPV vaccine series by the recommended age of 13.⁷

To increase cancer prevention among the next generation, there is strong interest in improving HPV vaccination rates. One method proposed to raise rates is to routinely initiate vaccination starting at age 9. Both the American Academy of Pediatrics (AAP) and the American Cancer Society (ACS) recommendations align with this approach.^8,9 Currently, fewer than 5% of the adolescents initiate HPV vaccination at age 9 or 10 years.¹⁰ While early evidence and anecdotal reports have been encouraging, the question of whether initiating vaccination at age 9 instead of 11–12 would lead to improvements in vaccination rates remains open. This Collection gathers existing and emerging evidence about the effect of initiating the HPV vaccine series prior to age 11 on timely HPV series completion, the acceptability of initiation in this age group among providers and families, and examples of HPV vaccination quality improvement programs that include an age 9 focus at the provider and health plan level.

Observational data from large national cohorts

Several studies in this collection examined factors associated with younger age at HPV vaccine initiation and the impact of earlier initiation on HPV vaccine series completion in large national datasets. Consistent across these studies was as follows: 1) Low baseline uptake of HPV vaccine at ages 9 to 10, ranging from 2% to 6.5%;^10–13 2) Higher uptake at ages 9 and 10 among children who were Black and Hispanic, living below poverty, or publicly insured;^10,11,13 and 3) Higher series completion associated with initiation at ages 9 to 10 by age 13^10,12,13 or by ages 13–17.¹¹

Minihan et al. used the NIS-Teen, a national survey of parents with vaccination status verified by medical record review, to examine the effect of age at HPV vaccine initiation on series completion at ages 13–17.¹¹ They found that 92% of the subjects initiating at ages 9–10 compared to 74% of those initiating at age 11 or older completed the series by their eighteenth birthday. A separate NIS-Teen analysis by Bednarczyk et al. noted up-to-date rates were higher (greater than 90%) among preteens initiating at age 9–10, compared to teens who initiated at age 11 or older.¹⁰ Saxena et al. used the Marketscan database, an administrative database including insurance claim data from approximately half of employer-sponsored insurance in the U.S., and the Medicaid database, an administrative database of publicly insured adolescents to examine the impact of initiating the series at ages 9–10 compared to 11–12 on completion by age 13.¹³ They found 76% of privately and 70% of publicly insured preteens who initiated the series at ages 9–10 completed the series by age 13 compared with 48% (private) and 40% (public) of those who started at age 11 or 12. These findings are consistent with a study published separately from this Collection by Goodman et al. that also used NIS-Teen and in which age 9 to 10 initiators were more likely to complete the series by age 13.¹⁴

Compared to the studies evaluating series completion by age 13 years, there was more variability in the evidence for time to series completion associated with initiation at ages 9 to 10. In the Saxena study,¹³ age 9- to 10-year-old publicly insured initiators had higher completion compared to 11- to 12-year-old initiators within 3–4 years of initiation (82% and 78%, respectively); however, there was no difference in time to completion in the privately insured cohort. Bednarczyk et al. found it took an average of 4 years for 85% of an age-based cohort to complete the vaccine series regardless of age at vaccine series initiation.¹⁰ The Goodman study, however, found age 9- to 10-year-old initiators were slightly less likely to complete the series in 3 years compared to 11- to 12-year-old initiators.¹⁴ While this is notable, completion by age 13 is used in quality metrics, and is more relevant when considering risk factors for HPV acquisition than time to completion.

Kajtezovic et al. examined the impact of initiating HPV vaccination prior to, at the same time as, or after the tetanus-diphtheria-pertussis booster (Tdap) or the meningococcal vaccines. Compared to adolescents receiving their adolescent vaccines at the same visit, those who initiated HPV vaccination prior to other vaccines had a 40% higher likelihood of on-time HPV completion, while those who initiated HPV vaccine after other vaccines had a 32% lower likelihood of completing the series on time.¹²

Two studies examined the effectiveness of younger versus older age at vaccination. A systematic review by Ellingson et al. indicated a higher effectiveness at younger ages of initiation, though data specific to ages 9–10 were limited.¹⁵ Ten-year follow-up data from the Indian randomized controlled trial of girls who received one, two, or three doses of quadrivalent vaccine at ages 10–18 found that 98% of the girls who received a single vaccine dose at ages 10–14 had detectable antibodies against HPV 16 and 18 ten years later, compared with 92% (HPV 16) and 94% (HPV18) for girls vaccinated at ages 15–18.¹⁶ Previous work by this group confirmed high efficacy against infection and cervical dysplasia.¹⁷

Quality improvement studies and acceptability

Several multi-level interventions have shown positive effects of initiating HPV vaccination at ages 9–10 on initiation and series completion rates.^18–20 Additional data in this Collection add to the evidence that vaccine initiation at ages 9 and 10 is acceptable to providers, payors, and parents and that quality improvement initiatives that include vaccine initiation at ages 9 and 10 may be an effective way to raise HPV vaccination rates across a variety of settings. Zorn et al. describe a provider-focused intervention to begin routine vaccination at age 9 in two pediatric clinics in Washington state serving a largely privately insured population.²¹ Initiation rates for 9-to-10-year old’s increased by more than 30% points following practice staff education, as well as updating prompts and electronic medical record order sets to start at age 9. As one provider in the study noted

I wish we had started vaccinating at age nine sooner. It is so important, and it’s made it so simple.

An additional study in Washington state examined the impact of Immunization Information System forecasting to prompt clinicians to say that HPV vaccination was due at age 9 and found a doubling of the weekly rate of HPV vaccine administration at age 9 years.²² O’Leary et al. describe an intervention in Federally Qualified Health Centers (FQHCs) in Colorado using standing orders for HPV vaccination. After the appearance of the best practice alert for HPV vaccination was moved from age 11 to age 9, initiation among 9- to 10-year-olds increased from 0.4% to a peak of > 30%.²³ A post-hoc analysis of a school-based vaccination program serving a rural population in Texas by Rodriguez et al. noted a 63% completion rate among adolescents initiating HPV vaccination at ages 9–10, compared to 76% at age 11, and 53% at age 12.²⁴

The success of these programs in improving initiation rates starting at age 9 years is encouraging evidence that HPV vaccination at age 9 is acceptable to many parents. Aragones et al. describe the results of a cross-sectional survey among Mexican- or Latino-identifying parents of children ages 9 to 10.²⁵ They found that, while 97% reported a well child check in the last 12 months, only 15% reported a conversation about HPV vaccination with their primary care provider. Following an educational intervention, 52% reported they wanted to vaccinate their child against HPV as soon as possible. A similar study by Kohler et al. also found a low prevalence of vaccine discussions at 9–10-year-old visits, but a high willingness of parents to engage in conversations with their children's health-care providers.²⁶

Interventions through health insurance plans may be another viable strategy to change practice and promote vaccination at ages 9–10 to meet quality metric goals. In their report, Foley et al. describe a national health plan learning collaborative where 25 of 28 plans chose HPV vaccine initiation at ages 9–10 as a focus for their quality improvement efforts.²⁷ Additional work by this team noted the feasibility and acceptability of adding recommendations at age 9 to clinical workflow, as well as the overall success of the interventions as noted by increased vaccination rates for adolescents at ages 9–10.²⁸

Communication

Many immunizing clinicians and immunization partners are either unaware of or confused by the varied framing of HPV vaccine initiation recommendations from the AAP, the Advisory Committee on Immunization Practices (ACIP), and the American Cancer Society. While all guidelines support vaccinations beginning at age 9, they vary in their specific language for routine administration. In his commentary, Dr. Sean O’Leary lays out the rationale for the AAP’s recommendation to start the series between ages 9 and 12 years, including improving uptake, increasing provider and parent flexibility, and evidence of a strong and durable immune response at younger ages. ^29(p9) While the above-mentioned quality improvement studies demonstrate provider acceptability to a routine age 9 recommendation, there is still much room for education and improvement. Lake et al. found that, among clinicians working at FQHCs who perform cervical cancer screening and also provide HPV vaccination for children and adolescents, 65% strongly recommend HPV vaccination starting at ages 9–10, lower than the 94% who strongly recommend vaccination at ages 11–12 and 96% who strongly recommend vaccinations at ages 13–18.³⁰

In their national cross-sectional survey, Kahn et al. described how different framings influenced the willingness of clinical staff to recommend HPV vaccine at ages 9 and 10.³¹ Participants read guideline messages framed as recommending HPV vaccine at “ages 11–12,” “ages 9–10,” or “starting at age 9.” More than half of participants were willing to routinely vaccinate at ages 9 and 10 when the recommendation was for “starting at age 9.” In contrast, only 37% were willing to vaccinate when the recommendation was framed using the current ACIP guidelines “starting HPV vaccination at age 11 or 12, which supports series completions before HPV exposure risk increases.”

Brewer et al. outline an adaptation of their evidence-based announcement approach tailored to age 9, including announcement that vaccination is due today, addressing concerns if the parent is hesitant, and trying again at a subsequent visit if the parent declines.³²

HPV vaccination has the potential to dramatically reduce HPV-associated precancers and cancers in the next generation. Yet, too few adolescents in the U.S. receive vaccination on time when it is most likely to provide cancer protection benefits. Initiating HPV vaccination at age 9 has the potential to increase both the number of adolescents receiving vaccination and the proportion of those vaccinated who complete the series on time.³³ This Collection adds to existing evidence for improved on-time completion of the HPV vaccine series, adding analyses from the Marketscan and Medicaid databases.^12,13 It also describes several successful quality improvement programs, providing blueprints for practices to implement a change to routinely recommending HPV vaccination starting at age 9.^21,23 Finally, the collection outlines the effect of messaging to clinicians on their attitudes toward the age of vaccination and describes potential opportunities and strategies for further improving HPV vaccination, including reducing future health-care disparities.^32–35

Conclusion

This collection offers evidence from large databases, quality improvement projects, and clinician surveys that starting HPV vaccination at age 9 years improves on-time series completion and can be adopted into routine practice in ways that are acceptable to parents and clinicians. Increasing the number of adolescents who begin the HPV vaccine series at age 9 may lead to improved cancer prevention by maximizing the number of people protected through on-time vaccination.

Additional information

Funding

The authors reported that they recieved no funding for this article.