Christopher D. Altman, PharmD

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, affecting some 79 million individuals.

 Infection with HPV has been linked to genital warts and 6 types of cancer.

Because the virus can clear on its own and cause no health problems, many people may be unaware they are infected and may unknowingly spread the virus to a partner. About 14 million new cases of HPV are documented in the United States each year.

 Individuals aged 15 to 24 years accounted for about 49% of new infections in 2013-2014. The remaining infections occured in adults 25 years and older: 35% of women and 45% of men aged 25 to 49 years had an HPV infection.

 Previously, vaccination was not recommended for patients in this age range, as there was no demonstrated benefit to HPV vaccination

Data from 2010 indicate that about 20% of adolescent females were vaccinated with at least 1 dose of the HPV vaccine, compared with 0.6% of adolescent males; up to 69% of adolescent females and 63% of adolescent males were vaccinated in 2017.

 The challenge of vaccinating patients continues, however, because of both social stigma surrounding the vaccine and guideline restrictions for vaccinating individuals older than 26 years. As of 2016, it was estimated that each day, more than 8000 Americans aged out of the recommendation,

 putting all of them at risk of contracting HPV and potentially experiencing its complications.

The HPV vaccine was first recommended for female patients in 2006, and administration to male patients was recommended in 2011. Currently, 1 HPV vaccine is available in the United States, the 9-valent HPV (9vHPV) vaccine (Gardasil 9; Merck).

 It was introduced to the market in 2015 and by the end of 2016, all other HPV vaccines were removed from the market.

The 9vHPV vaccine covers 9 strains of the HPV virus (6, 11, 16, 18, 31, 33, 45, 52, 58). It is administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh. The most commonly reported adverse reactions are injection-site pain and swelling. In addition, the package insert includes a warning for syncope and suggests monitoring patients for 15 minutes after injection.

PREVIOUS HPV VACCINATION RECOMMENDATIONS 

Routine HPV vaccination was previously recommended by the CDC’s Advisory Committee on Immunization Practices (ACIP) for all patients 11 to 12 years of age, with an option of starting as early as 9 years, using a 2-dose series given at 0 and 6 to 12 months. Catch-up vaccination was recommended for females and certain male populations through age 26 and all males through age 21. The recommendation also stated that males aged 22 to 26 years may be vaccinated based on individual clinical decision. Patients beginning the series after 15 years of age would receive a 3-dose series given at 0, 1 to 2 months, and 6 months. The recommendation for males up to age 26 specifically indicated that men who have sex with men, immunocompromised males, and HIV-positive males should be vaccinated.

All this begs the question, why not vaccinate patients older than 26 years?

The ACIP sought to answer that question and another one at their June 2019 meeting: First, should catch-up HPV vaccination be recommended for primary prevention of HPV infection and HPV-related disease for all persons through age 26 years? And second, should catch-up HPV vaccination be recommended for primary prevention of HPV infection and HPV-related disease for all persons aged 27 through 45 years?

 The first question was intended to synchronize female and male vaccination schedules, and the second to address vaccinating older patients. It is important to note that the FDA approved the 9vHPV vaccine for patients aged 9 to 45 years in October 2018.

Data presented at the meeting regarding the safety and immunogenicity of using the HPV vaccine in females aged 27 to 45 years of age showed that women in that age range are at risk of infection by the virus types included in the 9vHPV vaccine. The 9vHPV vaccine was also shown to be effective in women aged 27 to 45 years, regardless of age, with more than 99% seroconversion and an antibody response that was not inferior to that of younger patients. The vaccine also was shown to be well tolerated in this patient group and the findings supported the benefits of vaccinating patients aged 27 to 45 years of age.

Furthermore, the results of a cost analysis for harmonizing the catch-up indication for males and females up to age 26 indicated an estimated cost increase of about 5% for harmonizing the catch up to age 26. This cost increase was considered to be minimal. Conversely, the analysis showed that extending the recommended vaccination age to 45 years would produce small health benefits; the number needed to vaccinate to prevent 1 case of disease would be 40 times higher in patients through 45 years of age than in patients aged through 26 years. In addition, the results of the analysis showed that the cost to extend this recommendation to age 45 was significantly higher as compared with patients through age 26 years.

Based on these data and evidence, the ACIP voted to make the following changes to the recommendations: harmonizing the catch-up schedule to all patients through age 26, regardless of gender; and recommending that the HPV vaccine be provided for patients aged 27 to 45 years based on shared clinical decision making between the patient and their health care provider. These new recommendations are summarized in the table.

The ACIP also recognized the need to focus vaccination efforts on the adolescent population, as the vaccine is most effective before a patient is exposed to the virus. At this time, the ACIP is not recommending that patients over 26 years of be routinely screened; however, they specifically stated that patients at any age are at risk of contracting the virus and thus may benefit from vaccination. Persons in long-term, mutually monogamous sexual partnerships are unlikely to acquire new HPV infections.

HOW CAN PHARMACISTS HELP SUPPORT THESE NEW RECOMMENDATIONS? 

With these changes in recommendations for the HPV vaccine, pharmacists have an opportunity to engage new populations of patients and help provide needed protection. Reports have shown that 26% of adults aged 18 to 29 years do not have a primary care provider, and instead tend to use walk-in clinics and pharmacies for vaccines.

 As such, it is imperative that pharmacists are aware of the recommendation changes and that they engage this population.

Previously, pharmacists had to interpret individualized data to determine if a patient was at risk of acquiring HPV. This led to lower vaccination rates and increased incidence of HPV infection in men compared with women.

 The harmonization for male and female patients up to age 26 will help pharmacists in identifying at-risk patients and ensure that these patients are protected by receiving catch-up doses.

In addition, the new recommendation for vaccinating patients up to age 45 opens the door to pharmacists to help patients understand the value and importance of protection, and through shared decision making pharmacists can help patients determine if they should receiving the vaccine.

The new HPV recommendations may contribute to confusion for patients, and they may seek clarification from their pharmacist. As with any change in vaccine recommendations, pharmacists should be equipped to discuss these changes with their patients. Armed with this knowledge and as one of the most accessible health care providers, pharmacists have an opportunity to take the lead in their communities to help educate their patients and protect them from vaccine-preventable illnesses such as HPV. 

 is the clinical manager for immunizations at Rite Aid in Harrisburg, Pennsylvania.

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Articles

Previously, vaccination was not recommended for patients in a certain age range, as there was no demonstrated benefit to HPV vaccination; however, this is about to change.

HPV Update: Making Sense of the New ACIP Recommendations

In the confusing and changing world of immunizations, the question of which tetanus vaccine to provide challenges a pharmacist’s ability to protect patients. Add to that the difficulty in obtaining accurate immunization records for adult patients, and the struggle is amplified. Questions that plague pharmacists include, “What does a provider do when a patient cannot recall infor- mation regarding their last dose of tetanus?” “Did the patient receive the Tdap (tetanus, diphtheria toxoids, and pertussis) vaccine or a Td (tetanus and diphtheria toxoids) booster?” “Was the vaccine given during pregnancy?” “When was the last time the patient received the vaccine?” These questions are even more difficult for a pharmacist to answer in the moment.

Even with registry access and provider consultations, last-dose information may still be unavailable. With immunization rates for adults being low

, it is critical that pharmacists be able to make confident recommendations to their patients. The purpose of this article is to clear up any confusion pharmacists have regarding tetanus vaccines in adults and enable them to make informed decisions when immunizing patients and stocking their pharmacies.

Clostridium tetani, the microorganism that causes tetanus, enters the body through an open wound. Tetanus is caused by the exotoxin produced by the bacterium, which is released into the bloodstream and lymphatic system. Because the bacterium is anaerobic, it germinates in low-oxygen conditions. The exotoxin leads to nervous system disruption and causes muscle contractions and spasms.

 Characterized by overall muscle rigidity, commonly known as “lockjaw” due to a tightening of the jaw muscles, tetanus presents acutely and can be fatal if untreated.

The importance of tetanus vaccination in adults is evident when considering the incidence of dis- ease. Tetanus primarily occurs in adults at a median age of 44 years, and most patients are unvaccinated or inadequately vaccinated.

The Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for routine vaccination in adults is 1 dose of the Tdap vaccine, followed by a Td booster every 10 years for patients who did not receive at least 1 dose of the Tdap vaccine at or after age 11.

 Many adults, however, do not know which vaccine they received or when they received it. Furthermore, there are a range of tetanus-containing vaccines available for a pharmacist to provide patients (see table).

Pharmacists must help patients determine which vaccine they received previously so they can ensure the correct follow-up dose is administered and in stock, as most pharmacies do not carry multiple forms of the vaccine. This is espe- cially important because recommen- dations from the ACIP have slightly changed over the past 6 years due to changes in the recommendations for wound management administration and the addition of a recommendation for women to receive the Tdap vaccine during each pregnancy.

In 2013, data reviewed by the ACIP indicated that a second dose of Tdap was safe and effective for protection against tetanus and pertussis; however, this recommendation was not accepted because of cost concerns.

During their October 2018 meeting, the ACIP again reviewed the recommendation for a second dose of Tdap. This review stemmed from concerns regarding the lower vaccination rates seen in adults: Roughly just 20% of eligible adults are vaccinated with Tdap.

 This was coupled with the additional concern that adults are experiencing decreases in pertussis coverage over time, with waning immunity demonstrated 2 to 4 years after vaccination.

 In addition, the ACIP noted that many providers are not currently stocking multiple tetanus-containing vaccines. Broadening the recommendation to allow for any tetanus-containing vaccine would ease administration barriers for providers.

Also at the meeting, Sanofi Pasteur, maker of the Tdap vaccine Adacel, presented data showing that the administration of a repeated Adacel dose—8 to 12 years after an initial dose&mdash;was safe and effective. They also noted that health care providers are seeking guidance on which tetanus product to use in the event that a patient’s previous vaccination type is unknown. They concluded that approval of a repeated dose would help health care providers to more efficiently ensure adults are up-to-date with their vaccinations.

GlaxoSmithKline, maker of the Tdap vaccine Boostrix, pre- sented similar data. Repeated administration of Boostrix in patients aged 19 through 73 was shown to be both immunogenic and well tolerated.

Although the ACIP did not firmly recommend administration of Tdap every 10 years, following this meeting, the vaccine manufacturers are looking to the FDA for approval. Based on provider comments, it appears that embracing the administration of any tetanus-containing vaccine as the follow-up dose would improve vaccination rates for adults. This change would allow providers to determine which vaccine, Td or Tdap, to administer to the patient without having to worry about which vaccine was in stock. Until the ACIP updates their recommendations, or the FDA approves the repeated administration with any vaccine type, pharmacists should continue to follow the ACIP routine vaccination schedule for adults: 1 dose of the Tdap vaccine, followed by a Td booster every 10 years in patients who did not receive at least 1 dose of the Tdap vaccine at or after age 11. 

, is the clinical manager for immunizations at Rite Aid in Harrisburg, Pennsylvania.

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In the confusing and changing world of immunizations, the question of which tetanus vaccine to provide challenges a pharmacist's ability to protect patients.