Practicalities of Implementing HPV Vaccination in Your Pediatric Practice

Stan L. Block, MD, FAAP

In 2005, approximately 14% of the US population, or more than 42 million residents, were between 10 and 19 years of age.¹ Despite infrequent health care visits by this age group, approximately 10% to 25% of patients seen daily in a typical practice are adolescents. It is important for practitioners to know how to effectively approach the issue of HPV immunization with these patients who are at the target age for receiving the vaccine. This can be particularly challenging with male patients, because the quadrivalent (HPV4) vaccine was given a passive, permissive recommendation by the Advisory Committee on Immunization Practices (ACIP). The HPV4 vaccine was recently approved for a cancer indication for males as well as females, and additional data may become available that could influence the ACIP to reconsider its passive recommendation.

An effective, proper approach toward promoting the vaccine should be developed, not only with patients, but developed with nurses and other staff who have patient contact. Advocacy for the HPV vaccine for both genders should become part of the practice culture. Despite the experience in counseling for the vaccine in females, effective strategies cannot be universally applied to boys, who present some unique challenges. Providers must be aware of these challenges and strategies to overcome them, as recent studies of infection rates among more than 1,100 men aged 18 to 70 in the United States, Brazil, and Mexico have suggested that one-half of men in the general population may be infected with HPV and the incidence of a new genital HPV infection was 38.4 per 1,000 person-months.²

Common Parental Concerns about the HPV Vaccine

Several issues can influence parents’ decisions to immunize their children against HPV, and practitioners must be prepared to deal not only with reluctant parents, but also with the occasional hostile parent. Practitioners should keep the following considerations in mind when communicating the importance of HPV immunization to parents, clarifying misunderstandings and providing accurate information tactfully:^3-6

• Vaccine safety (excellent)
• Age of daughter or son (essential for apropos discussion)
• Effect on sexual behavior (none)
• Lack of HPV information (common)
• Disease prevention (excellent)
• Perceived need for vaccination (definite)
• Provider recommendation (assertive)

Vaccine safety

Safety has not been shown to be an issue with the HPV vaccine. Despite this, many parents continue to listen to sensational media reports that claim the vaccine can cause serious debilitating illness and death. Adverse events following the HPV4 vaccine are generally mild and transient. Approximately 50% of boys and girls will have a sore arm, low-grade fever, or headache after vaccination. Clinical trial data of 21,480 females aged 9 to 26 years and boys aged 9 to 16 years showed that this vaccine is associated with a higher frequency of injection site pain than placebo (81% for vaccine; 75% for placebo-aluminum; 45% for placebo-saline) but serious adverse events were not different in vaccine groups compared with placebo groups.⁷ No differences have been observed in the incidences of the most common nonserious adverse events: headaches and pyrexia. Furthermore, VAERS has received 14,072 reports for the HPV4 vaccine since its licensure and only 7% were serious adverse events, which is approximately one-half the average reported for licensed vaccines in general.⁸ However, it is important to explain to the patients that there is a slight chance that their child may faint and it is therefore essential that they remain seated for 15 minutes after being vaccinated to avoid a potential episode of syncope.

Some parents may have seen VAERS data about venous thromboembolisms (VTE) occurring after HPV4 vaccination. Of 40 cases, 30 had predisposing high-risk factors, including birth control pill use and blood-clotting disorders, precluding making a causative determination relating the VTE to the HPV vaccine. The CDC concluded that the VTE rate in HPV4 vaccine recipients was not different than the background rate. Furthermore, none of the cases in the report were younger than 15 years of age.

Practitioners should familiarize themselves with the available safety data, such as those published in Pediatric Infectious Disease Journal and Journal of the American Medical Association,^7,8 so they can assert with confidence that the vaccine is safe and counteract any negative effects from the Internet and other gossip sources.

Patient age

Giving the vaccine to adolescents at different ages can require different approaches; for example, dealing with pre-teens and their parents when the topic is preventing a sexually transmitted infection (STI) requires exploring their views and expectations and being sensitive to their attitudes and potential biases. Conversely, when a girl is 18 or 19 years old, it may be difficult to convince her that the vaccine is worthwhile. Often these adolescents are on their own, and they may refuse the vaccine simply because they hate to get shots. In addition, many parents believe vaccination can wait. Physicians must emphasize to parents that the vaccine is most effective if administered before the age of sexual activity, and waiting until the child is sexually active may increase their risk of irreversible exposure before vaccination. Although the relevance is not known, informing parents that antibody titers are higher after immunization at a younger age may convince them to have their child vaccinated at a younger age. With the recent addition of a cancer indication for the HPV quadrivalent vaccine in males, acceptance of the vaccine and receiving immunization during the recommended age range may be increased. The importance parents place on protecting against cancer was shown in a recent survey of low-income mothers, which revealed that their primary interest in having their daughters vaccinated was to prevent cancer.⁹

Effect on sexual behavior

Concerns about possible effects of the vaccine on sexual behavior must also be addressed. Parents may believe that consenting to the HPV vaccine is tantamount to condoning the child becoming sexually active. In addition, there are fears that after receiving the vaccine, the child will have increased sexual behavior, or will be tempted to have an earlier sexual debut. Some parents may benefit from the practitioner reminding them that after their teenager is given a Tdap vaccine, they do not feel compelled to step on rusty nails. Also, informing parents that numerous studies have shown that teenagers are not more likely to have sex or more sexual partners when condoms or emergency contraception are available in high schools may be helpful.^10-13

Lack of HPV information

HPV information is incomplete. Therefore, the practitioner may not be able to answer all the questions parents ask. Health care providers must, however, ensure that they have relevant current knowledge and can share it in a beneficial way with parents, particularly with supporting information on the need for the vaccination and the diseases it can prevent. Handouts, brochures from manufacturers, and CDC Vaccine Information Sheets are a few examples of readily available materials that may be helpful to physicians in providing information on HPV to patients.

Disease prevention

Understanding the data behind the rationale for an HPV vaccine for males, as well as the range of possible benefits to be acquired from the vaccine, is required to effectively support giving the HPV vaccine to both genders. The initial approval for use of the HPV4 vaccine in boys was for the prevention of genital warts. Genital warts are quite common, with a 10% lifetime risk for both men and women. HPV 6 and 11, for which antigens are included in the quadrivalent vaccine, are responsible for 90% of all genital warts. HPV4 is nearly 100% protective against genital warts in females and 90% protective in males. Although anal and penile cancer are very rare, HPV 16 and 18, also included in the HPV4 vaccine, cause approximately one-half of the infections at those sites.

In addition, common posterior oral cancers are increasing, and the HPV4 vaccine has the potential to protect against these cancers. In one study, 72% of these tumors were shown to have HPV 16 DNA.¹⁴ At the present time, vaccine trials for this indication are impractical because there is no intermediate endpoint that can be used to indicate efficacy; slow development of the cancers would require unacceptably long studies. Parents may, however, choose the vaccine based on possible, but not proven, benefit.

Need for the vaccine in males

Efficacy data on the vaccine is nearly 100% for vaccine types in females and 75% to 90% in males. An additional important justification for the vaccine in boys is that males are the vector for transmission to females. Some persons may dismiss the HPV vaccine for males because, at present, the diseases it can prevent are rare in men. However, transmitting the infection to women risks the development of some very common and serious diseases. For example, cervical cancer is the tenth most common cancer in women in the United States, with an incidence rate that is more than 10-fold greater than that for penile cancer.^15,16

If males are vaccinated, herd immunity following the HPV vaccine may significantly improve disease prevention in females. Herd immunity was observed in Australia, where reduced diagnoses of genital warts in both women and heterosexual men were seen after women began receiving the vaccine.¹⁷ In addition, impact models demonstrate that a greater reduction in cervical cancer would occur if both genders were vaccinated; in fact, a female-only vaccine policy has been calculated to be 25% to 40% percent less efficient.¹⁸

A female-only rubella vaccination program was tried unsuccessfully in the United Kingdom, which provides further support for a gender-neutral HPV vaccination approach.¹⁹

Practitioner recommendation

The most important key to vaccine acceptance is effective practitioner recommendation, which depends upon both knowledge and approach. Despite the ubiquitous sources of misinformation, it has been shown that parents not only look to physicians as their primary source for vaccine information, they consider them to be the most trustworthy source (Figure 1).²⁰ An assertive approach is beneficial: “Yes, I want you to get the vaccine, I think it’s important, it’s worthwhile, you should do it, it’s very safe.” Providers themselves must believe in immunization and have the data to support what they are saying.

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Prior to HPV vaccine approval, an educational intervention study showed that slightly more than one-half of the parents or guardians of boys and girls aged 10 to 15 years wanted HPV vaccination for their children (Figure 2).²¹ When asked again after receiving education about HPV and the vaccine, the proportion who said they would choose the vaccine increased to 75%. Therefore, the benefit of taking the time necessary to ensure that parents are adequately informed cannot be overemphasized.

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Special Counseling Considerations for the HPV Vaccine

Considering the brief amount of time typically available in the busy office, it is important to share the most salient information with parents. For example, they must understand that the vaccine should ideally be given at the targeted ages of 11 to 12 years. By age 15, 16, and 17, 30% to 50% of adolescents are sexually active, and may have been exposed to the HPV virus (Figure 3).^22,23 The vaccine is given to prevent HPV infection, not cure it. Therefore, it is best if children are vaccinated prior to becoming sexually active. However, data reveal that approximately 5.9% of in-school youth experience their sexual debut prior to the age of 13 years.²⁴ Therefore, infection is a possibility even at this young age. Moreover, the incidence of acquisition is highest 1 to 3 years immediately following sexual debut, making the idea of waiting to vaccinate even less desirable.

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Individual, cultural, family, and physician issues must be confronted when approaching HPV vaccination. Children 11 through 14 years of age have little, if any, knowledge of the HPV virus. Parents can be told that the lifetime probability of HPV infection is 50%, and parents may be shocked to learn that by the time their daughter is 14 to 19 years of age, there is an 18% probability that they are already infected with HPV.²⁵ Although numbers are important, practitioners must commit time to adequately discuss STIs with the family, rather than merely provide them with a list of statistics. This can be particularly trying if this need for counseling occurs when other situations are also exerting usual burdens on the practitioner’s time, such as an influenza epidemic.The subject of genital diseases can be an uncomfortable topic of discussion not only for parents, but for doctors as well. The tone the practitioner takes and the depth of the discussion are important issues to consider. With girls, it can be easier because the discussion can focus on cancer prevention without talking about sex. Discussing genital warts is more difficult, and more so with boys than with girls. The practitioner should decide whether to have the conversation with only the parents or with the child present as well. When the 10% lifetime risk for warts is explained, parents can be told that because the vaccine is 100% effective for genital warts caused by vaccine types for girls and 90% effective for boys, the lifetime risk decreases from 1 in 10 to 1 in 100 for females and 1 in 50 for males. Genital warts, however, typically do not become an issue until between the ages of 19 and 25 years. With durability data currently at 5 years, concern about the effectiveness of the vaccine after 8 or 10 years can be an issue adversely affecting acceptance of the vaccine. The prevailing opinion of those involved in studies of the mechanism and duration of immunity is that the HPV vaccine is durable.²⁶

A major challenge practitioners face is correcting the misinformation parents may have learned from the plethora of negative propaganda on the Internet, which has a substantial deleterious effect on vaccination efforts. Vaccine opponents can selectively retrieve VAERS reports and build horrific scenarios or create scholarly appearing articles with graphs and tables intending to portray an image of scientific validity. Many of these Web sites have respectable sounding names, such as the National Vaccine Information Center, which can convince parents of their legitimacy. Practitioners should become aware of scientifically valid sites such as the Vaccine Safety DataLink, to ensure that parents and adolescents are provided with accurate information to dispel this adverse publicity.

Issues unique to male vaccination

When vaccinating girls, it may be sufficient to tell them that you strongly recommend that they receive the HPV vaccine that day, and ask if they have any questions. For boys, ask patients and families if they are interested in getting the vaccine and, if not, why; then guide them to understanding the rationale and benefits for using the vaccine. There may be alternative ways to finance the vaccine for males if insurance does not cover it and the patient is not VFC-eligible.

When talking to young adult males, studies have shown that if the HPV vaccine is offered based on warts prevention only, 42% will accept the vaccine.²⁷ Framing the benefit as cancer prevention increases uptake to 60%. Therefore, cancer prevention should not be overlooked when offering the vaccine to males. Although these cancers are rare, 50% of anal and penile cancers are caused by HPV 16 and 18. Explain that the FDA-approved label was expanded to include protection against anal cancer, and it is not implausible to expect that indications could be further expanded to include protection against penile cancer.

Parents can also consider the potential for herd immunity for females when deciding on vaccination for their sons. Most parents would object to their son transmitting a disease that could possibly be fatal or require chemotherapy. Asking “do you want to prevent your son from inadvertently spreading a deadly precancer or cancer?” may help convince parents of the importance of the vaccine.

Many boys, like girls, are tremulous about shots, and adding additional shots during their office visit can significantly escalate their stress. Mothers are typically the driving force for accepting vaccinations. Therefore, if mothers are aware of the benefits, they can usually properly motivate their sons.

Logistic Issues Associated with the HPV Vaccine

Taking advantage of all possible vaccination opportunities is important. Vaccines should be included in the list of “vital signs” on the patient’s medical record, which can facilitate checking if they are up-to-date on vaccinations at each visit. Electronic medical records are useful for managing this information. If the vaccines are not up-to-date, the nurse and the doctor are immediately aware when they check that section of the record. Having this reminder can aid in increasing vaccination rates. In addition to being alert for reminders in the records, the nursing staff can talk with the patients about their vaccines prior to the doctor, and inquire whether they intend to get specific vaccines at the current visit. If the girl or boy is eligible for the HPV vaccine, the nurse can give them a handout to read while they are waiting for the doctor. Not only should vaccine status be checked when the patient is in the clinic for a well patient visit, the vaccine can be given when the patient is mildly ill. Having vaccine status as a “vital sign” will help ensure that these opportunities are not missed.

Research has shown that HPV vaccination can be given at the same time as Tdap and meningococcal vaccines in girls and boys aged 11 to 12 years and up to 15 years of age.²⁸ In addition, there are no contraindications to giving the HPV and flu vaccines concomitantly. Whether giving 1 or 4 shots during the same office visit, practitioners should ensure that their patients wait in the office for 15 minutes after receiving the vaccine to minimize the chances of vasovagal syncope occurring. In clinical trials, the subjects remained stationary in the office for 30 minutes, and few cases of syncope were reported. However, when patients were allowed to leave immediately, occasional cases of profound vasovagal syncope have been reported and, rarely, vasovagal seizure has occurred.

Because of this risk, the AAP and ACIP recommend a routine 15-minute waiting period, which is also included in the prescribing information for both vaccines. Practices often complain, however, that they are too busy and lack the space to comply with this recommendation. In addition to the risk to the patient, a syncopal event presents a medico-legal hazard to the practice, as adolescents have experienced traumatic falls resulting from too early ambulation, with reports of nose and skull fractures, subdural hematomas, and dental injuries among other serious consequences.⁷ Therefore, it is incumbent upon practitioners to ensure that the 15-minute wait is an office policy that is strictly enforced for any adolescent vaccine.

The logistics of completing the 3-dose series when there is only one routine checkup in children 11 and 12 years of age can be cumbersome. Completion of the series is necessary to establish long-term protection, which current data indicate continues for more than 5 years in adult women.²⁸ Data supporting longer protection are expected in the future, as well as data on durability of protection in children who are vaccinated at 11 and 12 years of age.

Other Issues Related to the Vaccination of Adolescents

As with any vaccine, storage and cost issues can influence the practitioner’s acceptance of the HPV vaccine for males. Transportation can be a problem for teenagers, and sometimes adolescents less than 18 years of age are in the office without a legal guardian available. Nurses can get parental approval over the telephone if needed. However, if there is reluctance the vaccination must be postponed. Explain the details about the HPV vaccine to the adolescent and give them a parental permission slip with a Vaccine Information Statement to have signed and bring on the next visit. In private offices the HPV vaccine probably should not be given to minors without parental consent unless the minor is legally emancipated. These laws may vary by state.

The current permissive ACIP recommendation for vaccination of boys was accompanied by a resolution that allows 100% HPV4 vaccine coverage by the Vaccines for Children (VFC) program for qualified boys. Coverage policies of commercial insurance companies vary from state to state and from plan to plan, although the majority have some coverage for boys. If a child’s insurance does not provide coverage for the HPV vaccine, or if the insurance plan has limited coverage for vaccines that have been reached or exceeded, the child may qualify for VFC because they are uninsured for that vaccine. Regardless of coverage, a male can always receive the vaccine at no cost at a federally qualified health center. Practitioners should check with their state regulations and VFC providers to verify that they are allowed to use VFC stock vaccines in these situations. The structure of Health Savings Account (HSA) plans with high deductibles often precludes their feasibility for supporting vaccinations for children. In addition, often patients with HSAs are not eligible for VFC vaccines, because they are considered to be fully insured. Vaccine manufacturers also have programs for vaccine reimbursement for those who cannot afford it.

Conclusion

Three key reasons to vaccinate males against HPV:

1. Protection against genital warts
2. Protection against anal cancers and precancers
3. Herd immunity (protection of females, unproven)

Despite the negative press, studies on HPV vaccine acceptance show:

• High levels of parental interest in HPV vaccination for children
• Minimal concern about vaccination for STIs
• Parents are primarily motivated to protect their child against cancer

Salient advice for practitioners can be summarized in 4 points:

• The most effective time to vaccinate is before risk of exposure
• Consider vaccinating preteens/adolescents early, while they are still making regular office visits and their immune response is vigorous
• Make vaccine status a routine “vital sign”
• The physician’s recommendation regarding vaccination is the most important—know the facts and present them convincingly

The practitioner should facilitate communication with patients and their parents using shared decision making, focusing on:^29,30

• Learning parental/patient concerns and answering their questions
• Informing about the risks and benefits of the vaccine
• Showing sensitivity, especially if the child is in the room
• Respectfully addressing beliefs, concerns, knowledge, and preferences
• Discussing viewpoints to increase persuasiveness
• Empowering the parent towards making an informed decision
• Reinitiating conversation as needed
• Emphasizing disease prevention rather than mode of transmission

References

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