The Hidden Adherence Problem: HPV Vaccination Series Completion Is Not as Easy as 1, 2, 3

Pharmacists can help improve vaccination completion rates.

The recent discovery of 6 vials of smallpox in a government laboratory just outside Washington, DC,¹ is a reminder of the public health impact that immunizations have had in the past century on reducing or eliminating serious infectious diseases. Smallpox was declared eradicated in 1980 and parents today no longer fear that their children will die from diphtheria or become disabled from polio.

Despite these successes, vaccination rates are still not optimal. Healthy People 2020 is a government program that establishes population health objectives every 10 years, including target vaccination rates.² The Healthy People 2020 target for tetanus-diptheria-acellular pertussis, meningococcal conjugate, and human papillovirus (HPV) is 80%, and for varicella it is 90%. The baseline vaccination rates in 2008 were 46.7%, 43.9%, 16.6%, and 36.7%, respectively.

Vaccines that require more than 1 dose, that is, a series of repeat doses over time, are particularly challenging.² We don’t have good evidence on whether patients who only complete a portion of the series are fully immunized, and we must therefore assume that partial series completion may not prevent the infectious disease that the vaccination targets. We will use HPV vaccination as an example to explore what factors are associated with vaccine uptake and series completion, what can be done to improve coverage rates, and what role the pharmacist can play.

Background on HPV

HPV infection is the most common sexually transmitted disease in the United States and occurs in approximately 50% of sexual active people at least once in their lifetime.³ The downstream consequences of these infections are serious. HPV types 16 and 18 cause approximately 70% of cervical cancer and the majority of other HPV-related cancers (vaginal, anal, and vulvar).⁴ HPV types 6 and 11 cause approximately 90% of genital warts.

Two HPV vaccines are approved for use in the United States; both are effective at preventing HPV types 16 and 18 and one is also effective at preventing types 6 and 11 (Cervarix [GSK], a bivalent vaccine and Gardasil [Merck], a quadrivalent vaccine). These vaccines are given as a series of 3 IM doses with the second dose given 1 or 2 months after the initial dose and the third dose given 6 months after the initial dose. They are generally well tolerated and close to 100% effective in preventing vaccine-type HPV infections in adolescents and young adults not previously exposed to HPV.

The potential public health impact of HPV vaccinations to significantly reduce the morbidity, mortality, and costs of HPV-related cancers is enormous. While HPV vaccination coverage in the United States has improved since the first vaccine was introduced in 2006, the number of eligible patients who complete the 3-dose vaccination series is low compared with HPV vaccination rates in other countries and to the coverage rates for other adolescent vaccines in the United States. The National Immunization Survey for Teens (NIS-Teen), conducted annually by the Centers for Disease Control and Prevention (CDC), showed in their 2013 survey that HPV vaccination series completion rates have continued to increase each year but the rates are still low.⁵ For example, in 2013, 57% of adolescent girls 13 to 17 years received the first dose of the vaccine, 48% received 2 doses, and only 38% completed the 3 dose series. The 2013 series completion rates for adolescent boys were even worse, with an overall series completion rate of 14%. The trajectory of these rates from 2006 to 2013 suggests that the Healthy People 2020 goal of an 80% completion rate will not be achieved unless the rate of series completion increases over the next 5 years.

Factors Associated With HPV Vaccine Uptake and Series Completion

A recent systematic review evaluating factors associated with uptake in teenage girls (9 to 18 years) identified 25 unique studies, most of them conducted in the United States (20/25 studies), and most with moderate or higher risk of bias after critical appraisal.⁶ Older age, history of other pediatric vaccinations, and previous health care utilization were consistently predictors of vaccine initiation and uptake. Ethnicity (Caucasian race) and having public or private health insurance were predictors of vaccine initiation and uptake in some studies, but showed no significant association in others. For series completion, ethnicity (Caucasian race) and having public or private insurance were consistent predictors of series completion.

In addition, the authors reported that uptake and series completion rates vary significantly across countries, with the United Kingdom and Portugal achieving 80% coverage rates where vaccines are free and delivered through school-based programs. This study excluded males and adult females over 17 years old. There are fewer studies addressing males and older females (18 to 26 years) and it’s not known to what extent studies of adolescent boys can be generalized to adolescent boys or adult females.

For adolescent girls whose parents reported no intention of getting their daughters an HPV vaccination in the next year, the CDC survey identified the top 5 reasons that parents identified for why their daughters would remain unvaccinated: 1) vaccine not needed (19.1%); 2) vaccine not recommended (by provider) (14.2%); 3) vaccine safety concerns (13.1%); 4) lack of knowledge about the vaccine (12.6%); and 5) daughter is not sexually active (10.1%).⁴

Opportunities to Improve Uptake and Series Completion

The CDC has estimated that going from the 2012 3-dose HPV vaccination coverage rate of 33% to a 3-dose coverage rate of 80% would prevent an additional 53,000 cases of cervical cancer over the lifetime of girls younger than 13 years.⁴ For every year that increases in 3-dose coverage is delayed, another 4400 women will go on to develop cervical cancer. Three key areas were identified by the CDC4 that must be addressed to improve vaccination coverage:

• Education of parents: Additional educational materials can be obtained on the CDC Vaccine website (www.cdc.gov/vaccines/) or on the Children’s Hospital of Philadelphia Vaccine Education Center website (www.chop.edu/service/vaccine-education-center/home.html).
• Improving the consistency and strength of HPV vaccination recommendations by health care providers: Studies that have evaluated health care provider communications to patients and their parents have shown that HPV vaccination recommendations are weaker than they are for other pediatric vaccinations and sometimes don’t occur at all.
• Missed vaccination opportunities need to be reduced: The 2012 CDC survey reported that 84% of unvaccinated girls had a health care encounter where another vaccine was administered. If the first dose of the HPV vaccine had been administered along with other vaccinations, the coverage rate for first dose would have been 92.6%. In addition, health care providers can facilitate completion of second and third doses by proactively scheduling follow-up visits and sending reminders to “no shows.”

What Can the Community Pharmacist Do to Improve HPV Vaccination Uptake and Series Completion?

Community pharmacies have been identified as “an especially promising novel setting for HPV vaccine delivery.”⁷ Pharmacies now have a proven track record in vaccine administration, offer better access for patients (longer hours, no appointment), and have the ability to adjudicate claims in real time.⁶ While this concept is appealing, individual states regulate whether and under what conditions pharmacists can administer HPV vaccinations.⁵ Based on a 2012 survey, most states (80%) allow pharmacists to administer HPV vaccinations to females 18 to 26 years old and most states (59%) allow vaccination in females 9 to 18 years old. But for younger patients, many states require provisions such as a protocol agreed to by the patient’s physician or a physician prescription. Because this is a rapidly changing landscape and policy changes have occurred since the 2012 survey was conducted, it is recommended that pharmacists contact the board of pharmacy in their state to ensure access to the latest information on state pharmacy regulations for HPV vaccine delivery.

Pharmacists have the training and capabilities to improve the uptake and series completion rates for HPV vaccinations and to play a key role in addressing a serious public health issue. The American Pharmacists Association has proposed an ultimate goal of an “Immunization Neighborhood” whose purpose would be “Collaboration, Coordination, and Communication among immunization stakeholders dedicated to meeting the immunization needs of the patient and protecting the community from vaccine preventable diseases.”⁸ As with other vaccinations, it will be important for pharmacists to work closely with the patient’s primary care provider, which in most cases will be their pediatrician. In some cases that may mean that the first dose is administered by the primary care provider and follow-up doses administered by the pharmacist for the convenience of the parent and patient. It will also be important for pharmacists to understand the nuances of adolescent vaccination reimbursement in general, including HPV vaccination reimbursement. For example, pharmacists may not be eligible for reimbursement for adolescents who receive their vaccine through the CDC’s Vaccines for Children Program. Pharmacists may also be unable to adjuducate claims that are covered by the medical rather than the pharmacy benefit. If we are able to solve the challenges of differing statewide authority to vaccinate, coordination of vaccination with the primary care physician’s office, and claims adjudication through both the private and public health insurance systems, pharmacists will be able to assist our nation achieve the Healthy People 2020 3-dose vaccine coverage goal of 80% as well as other vaccine goals.

Newell McElwee, PharmD, MSPH, is pharmacist and epidemiologist with over 25 years of experience in outcomes research. Newell is currently the executive director of the US Outcomes Research group in the Center for Observational and Real-World Evidence at Merck & Co, Inc. Prior to joining Merck in April 2009, he was vice president, outcomes research at Pfizer. Newell has been active and has had leadership roles in various professional societies related to outcomes research and recently completed a term on the ISPOR Board of Directors (2011-13). He is also currently a member of the Agency for Healthcare Research and Quality (AHRQ) National Advisory Council, the AHRQ CERTs Steering Committee, the AMCP Format Executive Committee, FMCP Board of Directors, and the IOM Roundtable on the Promotion of Health Equity and Elimination of Health Disparities. Newell earned his BS in pharmacy at Northeast Louisiana University, his PharmD at Mercer University, and his MSPH in epidemiology at the University of Utah. He also completed an ASHP residency in clinical pharmacy and a postdoctoral fellowship in clinical pharmacology and toxicology.Karen Woomer, MBA, is an account executive at Merck. She previously served as executive business manager for Merck & Co, Inc. Karen earned her MBA in marketing from the University of Pittsburgh Joseph M. Katz Graduate School of Business.

References

• Fountain H. Six vials of smallpox discovered in laboratory near Washington. New York Times. July 8, 2014.
• Immunization and infectious diseases. Healthy People 2020 website. www.healthypeople.gov/2020/topicsobjectives2020/overview.aspx?topicid=23. Accessed July 19, 2014.
• Human papillomavirus (HPV) infection. Sexually Transmitted Diseases Treatment Guidelines, 2010. www.cdc.gov/std/treatment/2010/hpv.htm. Accessed August 3, 2014.
• Centers for Disease Control and Prevention. Human papillomavirus vaccination coverage among adolescent girls, 2007-2012, and post licensure vaccine safety monitoring, 2006-2013—United States. MMMR Morb Mort Wkly Rep. 2013;62:591-595.
• Centers for Disease Control and Prevention. Human papillomavirus vaccination coverage among adolescents, 2007-2013, and post licensure vaccine safety monitoring, 2006-2014—United States. Morb Mort Wkly Rep. 2014; 63:620-624.
• Kessels SJ, Marshall HS, Watson M, Braunack-Mayer AJ, Reuzel R, Tooher RL. Factors associated with HPV vaccine uptake in teenage girls: a systematic review. Vaccine. 2012;30:3546-3556.
• Brewer NT, Chung JK, Baker HM, Rothholz MC, Smith JS. Pharmacist authority to provide HPV vaccine: novel partners in cancer prevention. Gynecol Oncol. 2014;132(suppl 1):S3-S8.
• Rothholtz M. Presentation to the CDC Advisory Committee on Immunization Practices. June 20, 2013. www.cdc.gov/vaccines/acip/meetings/slides-jun-2013.html.