In the United States, vaccination recommendations for children and adolescents are developed through collaboration of two groups of experts: the American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID) and the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). While the recommendations are usually “harmonized,” meaning the same or nearly so, the recommendations about human papillomavirus (HPV) vaccine differ in an important way.

During this Cervical Health Awareness Month, we asked Dr. Sean O’Leary, Chair of AAP’s COID, to explain the “what” and “why” related to this recommendation difference.

For HPV vaccination, in what way is the ACIP recommendation different from that of AAP?

In short, AAP emphasizes series initiation at an earlier age, as the 2018-2021 AAP Red Book first spelled out:

“The AAP and the ACIP on behalf of CDC recommend routine HPV vaccination for females and males. The AAP recommends starting the series between 9 and 12 years, at an age that the provider deems optimal for acceptance and completion of the vaccination series. The ACIP recommends starting the series at age 11 or 12 years and states that vaccination can be administered starting at 9 years.”

Both recommendations seem to support routine universal HPV vaccination. Is that correct?

Absolutely! CDC and AAP both see HPV vaccine as an important routine vaccination because the vaccine is safe and effective, preventing most cases of HPV infection if given before exposure to the virus. HPV infection prevention, in turn, leads to prevention of cervical dysplasia and cancer; the data on the impact on cervical cancer grow stronger every year. Healthcare personnel often do not realize that in the U.S., HPV-related mortality far surpasses the mortality from tetanus, diphtheria, pertussis and meningococcal disease combined. Each year, about 4,000 deaths are the result of cervical cancer; most are preventable through pre-exposure vaccination. We expect vaccination to prevent other HPV-associated cancers, such as oropharyngeal cancer, too. Further, we also are thrilled with the evidence that HPV vaccination prevents anogenital warts and respiratory papillomatosis.

Why does AAP emphasize starting the series sooner than the CDC recommendation for 11 to 12 years of age?

In short, we see recommending HPV vaccine at 9 or 10 years of age to increase vaccination coverage. We are aware that, despite the vaccine’s remarkable record of safety and efficacy, HPV vaccination coverage is well below national goals. As detailed in the September 2022 “Technically Speaking” column, the most recent National Immunization Survey-Teen showed uptake of tetanus diphtheria acellular pertussis (Tdap) vaccine was 90.1% and the first dose of quadrivalent meningococcal (MenACWY) was 89.3%, whereas HPV initiation was 75.1% and completion was 58.6%.

What were the considerations that led to AAP’s decision to recommend starting the HPV vaccine series before 11 years of age?

Four considerations were critical to this decision:

  1. The earlier age recommendation allows for more flexibility introducing the vaccine.
  2. For families that want to limit the number of vaccines administered at a single visit, starting HPV vaccination before age 11 provides an opportunity.
  3. Anecdotally, we’ve heard that initiating HPV vaccine earlier made it easier to disentangle HPV vaccination and discussions of sexuality, a known barrier for many providers. 
  4. Many physicians defer recommending HPV vaccine at 11 to 12 years of age because they have experienced disheartening responses in the past. By changing the timing of the recommendation to an earlier timeframe, they have the option to do something different, which may lead to different results.

There have been some changes since the initial HPV recommendation in 2007. Please tell us how those changes weighed into the AAP’s recommendation.

Two main changes to the practice of medicine and HPV vaccination offer reasons to abandon the 11- to 12-year-old “adolescent platform” when it comes to HPV vaccination:

  1. Implementation of annual well visits: In 1996, well child visits typically did not occur beyond kindergarten, so the CDC, AAP, and American Academy of Family Physicians (AAFP) sought to establish a routine visit for 11- to 12-year-olds to provide an opportunity to catch up on routine vaccinations, especially hepatitis B vaccine. Later, as more adolescent vaccines became available, like meningococcal, Tdap, and, of course, HPV, this became even more important. Now, though, the AAP and AAFP recommend routine annual well child visits, and 79% of 6- to 11-year-olds attend such visits, making the so-called “adolescent platform” of vaccines timed to a single visit at 11 to 12 years of age less necessary.
  2. Additional data: Second, when the initial HPV vaccination recommendation was made in 2007, we had excellent data on the safety and immunogenicity of HPV vaccine, but we did not have data on the potential for waning immunity. Thus, the age 11 or 12 recommendation was considered a good “middle ground” for vaccination because it would occur before most adolescents became sexually active, but was still close enough to provide protection through the years of highest risk, during late teens and early 20s. We now know that antibody levels plateau approximately 18 to 24 months after series completion without further significant waning. Further, we know that immune responses at younger ages are robust.

Is there evidence suggesting that earlier initiation leads to higher HPV vaccination uptake?

Observational studies support earlier initiation. For example, a retrospective study showed that adolescents who started the HPV vaccine series at age 9 or 10 were 22 times more likely to complete the two-dose series by age 15 compared with those who initiated the series at age 11 or 12. Likewise, reports from quality improvement initiatives have shown rapid uptake of HPV vaccine prior to age 11.

A randomized trial comparing series initiation at 9 or 10 years versus 11 or 12 years, in which I am involved, is currently ongoing. Results are expected in the next few years.

Conclusion

The AAP and CDC share the goal of preventing HPV-related cancers and other diseases by optimizing coverage with HPV vaccine. HPV vaccination at 9 or 10 years of age is just one of many strategies to increase HPV vaccine uptake (e.g., reminder/recall, standing orders, presumptive recommendations). However, preliminary evidence suggests that it may be effective; therefore, it offers another important tool in the box as we seek to position our patients for healthy futures.

Editor’s note: Sean O’Leary, MD, MPH, FAAP, practices in the Department of Pediatrics at the University of Colorado Anschutz Medical Campus and the Adult and Child Center for Health Outcomes Research and Delivery Science (ACCORDS) at the University of Colorado School of Medicine/Children’s Hospital Colorado in Aurora, Colorado. Dr. O’Leary indicated that he has no financial conflicts of interest. He is a co-investigator on an NIH-funded clinical trial comparing introduction of HPV vaccine at age 9 or 10 to introduction at 11 or 12, as mentioned in the commentary (Kempe, Szilagyi, multi-PI’s, 5R01 CA240649-03).

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

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