Adjusted vaccine schedules for patients with special needs including patients with immunocompromising conditions is also provided by the FDA. Patients with HIV, for example, should receive a 3-dose series at 0 (baseline), 1 to 2 months, and 6 months after the first dose.16 For children with a history of sexual abuse or assault, the FDA recommends routine HPV vaccination beginning at 9 years of age.16 HPV vaccination should not be given during pregnancy; however, no interventions are needed if a woman is given the vaccine during an unrecognized pregnancy. Pregnancy testing before vaccination is not recommended.16

In 2018, the FDA recommended expanding the approval of the vaccine to include women and men aged 27 through 45 years.6 Although the vaccine is approved for people through aged 45 years, the ACIP does not recommend routine vaccination of people older than 26 years at this time. In a 10 to 4 vote, the committee recommended that patients aged 27 to 45 years undergo shared decision making following a conversation with their healthcare provider.17 Adults older than 45 years who had not been previously vaccinated are advised against receiving the vaccine as it is not licensed in this age group.6

The FDA also approved safety data allowing Merck to provide the 9-valent vaccination to patients who had previously received the 4-valent Gardasil vaccine.6


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Barriers to Vaccination

Despite the benefits of the HPV vaccine, adoption of the vaccination program has been slower in the United States than in European countries. In 2017, immunization experts noted that if healthcare providers in the United States were able to increase HPV vaccination rates to 80%, an estimated additional 53,000 cases of cervical cancer could be prevented.18

The HPV vaccination is available in all 50 states, Washington DC, and the 8 United States territories through the federal Vaccines for Children Program (VCP). This program provides vaccines to children up to age 19 who are underinsured, uninsured, Alaskan-Native or Native American, and children covered by Medicaid.19 Patterns of HPV vaccination have shown that rates are higher among children enrolled in Medicaid compared with children with private insurance.4 These disparities may represent “vaccine hesitancy,” which has been seen among more educated, higher-socioeconomic level individuals. The national vaccine coverage study found that children are more likely to receive concomitant vaccinations if they are dosed at a younger age and if their parents received a recommendation from a healthcare provider.4 The investigators suggest that this may be representative of parents being more accepting of the vaccination when it is given in the early stages of puberty when they are less concerned about their child’s sexuality.4

An additional barrier to vaccination includes a general lack of knowledge about HPV among adults, as well as its relationship to cancer. The Health Information National Trends Survey to assess the knowledge of HPV and its association with penile cancer highlighted this lack of knowledge.20 Of 3376 respondents to the telephone survey performed by the National Cancer Institute, 64.4% had heard of HPV, but only 29.5% were aware that it could cause penile cancer.20 The survey also included questions to identify social determinants of health. Individuals who were significantly less likely to have heard of HPV included older people; African-American, Asian, and “other race”; married; from lower education brackets; and without internet access.20

Finally, individuals who are aware of HPV may have a general misconception regarding the safety of the vaccination. The World Health Organization (WHO) has been monitoring and reviewing the safety and adverse event reports of vaccinations over the last decade.21 Overall, the WHO considers this to be a safe and effective vaccination. To date, data has failed to show an association with any of the following significant effects: autoimmune conditions, thromboembolism, neurologic diseases, Bell’s palsy, Guillain-Barrè syndrome, regional complex pain syndrome, orthostatic tachycardia syndrome, or death.22

To help boost the adoption of HPV vaccinations, the ACIP has recommended that the vaccine be given concomitantly with the MenACWY and Tdap booster at age 11 or 12 years,4,23 typically given prior to entry to seventh or eighth grade. While 48 states require the Tdap booster prior to matriculation, only 33 states require the MenACWY vaccination and only 2 states and Washington DC require HPV vaccination.24,25 The American Academy of Pediatrics has issued an HPV vaccine implementation guidance document, which states that healthcare providers should provide a strong recommendation for bundling these vaccinations.26 They note that the healthcare provider’s recommendation for the HPV vaccine is the strongest predictor of vaccine acceptance.26 This recommendation should be framed as a vaccination that can prevent HPV-related cancer deaths rather than a vaccine against a sexually transmitted disease. When parents refuse the vaccine, it is important to understand their reasoning and to maintain a supportive relationship. 

Patient Education

When providing patient education regarding the vaccination, healthcare providers should review the safety and efficacy of the vaccination. It is important that patients understand that the vaccine is not therapeutic and will not cure an already HPV-infected individual. However, even if the patient has had a previous abnormal Pap test, a history of genital warts, or positive HPV DNA testing, they should be offered vaccination. Ideally, patients should be vaccinated before the onset of sexual activity; however, people who have already been infected with one or more HPV types will still be protected from other HPV types covered by the vaccine. As such, HPV vaccine should be offered and administered to people who are already sexually active.

One major consideration vital to the discussion is cost. With the lack of a clear recommendation for vaccination in patients aged 27 to 45 years, there will be out-of-pocket costs to consider. According to the CDC, the cost of each injection can range from $140.59 to $227.93 and may present a significant barrier to vaccination in this age population.27 Providers can help their patients navigate this barrier with awareness of additional options for cost assistance. Drug assistance programs are in place from the manufacturers. There are also many Planned Parenthood locations that offer free or reduced-cost injections. Patients may also have access to injections through their university student health clinics and local health departments.28

In May 2018, the WHO launched a “Call For Action: Toward Cervical Cancer Elimination,” urging an “upscaling of worldwide vaccination” in an effort to eliminate HPV-mediated cervical cancers.29 In an article published in The Lancet, the researchers used a statistical trends analysis and modeling study aimed to identify the earliest years by which cervical cancer rates could be considered as possible “elimination thresholds.”30 Their analysis found that widespread coverage of both HPV vaccination and cervical screening from 2020 onwards has the potential to avert up to 12.5 to 13.4 million cervical cancer cases by 2069.30

On a global scale, the current demand for the HPV vaccine exceeds the available supply. The United Nations Children’s Fund (UNICEF) supply division reported that the current supply through UNICEF is not sufficient to meet the increased demand for the HPV vaccine.31 Demand is projected to reach 35.8 million doses in 2020 and up to 120 million doses by 2030.31 UNICEF is currently working to secure supplies for 2020 and beyond.29 Furthermore, many countries have delayed full-scale HPV vaccine introduction in order to address competing health priorities, as well as concerns about pricing/affordability, which has led to decreased production from suppliers.31

In keeping with the WHO’s call for action, several countries have trialed the durability and efficacy of a 1- or 2-dose vaccination series.13,32,33 Kreimer, et al reported that “antibody levels after 1 dose, although lower than levels elicited by 3 doses, were 9-times higher than levels elicited by natural infection.”33 Of note, these levels remained constant over the 7-year follow-up period, suggesting a durable protection provided to patients even with a single dose of the vaccine. These studies show promising results that would greatly reduce program costs in many countries.

Although some of these studies were completed with the bivalent vaccination, there is data to suggest cross-protection of additional subtypes.13,33 With HPV16 and HPV18 accounting for 72% of all HPV-associated cancers worldwide, these results from a reduced dosage schedule of the bivalent HPV vaccine are important for policymakers to consider.9 Requiring only 1 dose may greatly reduce the preventable burden of disease in countries that otherwise cannot afford screening or vaccination.21            

Summary                                                                                               

Healthcare providers should speak with parents and adolescent patients about the safety and efficacy of HPV vaccination. The 9vHPV has substantial proven immunogenicity for preventing HPV-associated cancers, as well as the development of genital warts. With almost half of new HPV infections occurring in adults 25 years or older, it is vital that providers are aware of the expanded indications from the FDA and vaccination recommendations from the CDC’s ACIP. It is important to review the potential benefits of vaccination, especially when given at a young age, to both parents and adolescent patients.  

Amanda P. Stanton, PA-C, is an instructor in obstetrics and gynecology at Mayo Clinic College of Medicine and Science in Jacksonville, Florida.

References

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