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JAMA
Rodney Willoughby, MD, a pediatric infectious disease specialist at the Medical College of Wisconsin, can’t help thinking about the future—a future in which thousands of men and women develop precancerous or cancerous lesions that could have been prevented had they been vaccinated against the human papillomavirus (HPV) as 11- or 12-year-olds.
“The family practitioners and pediatricians do a really bad job in promoting HPV vaccination for a variety of reasons,” said Willoughby, a member of the Advisory Committee on Immunization Practices’ (ACIP) working group on the HPV vaccine and the American Academy of Pediatrics’ Committee on Infectious Diseases. “We recognize that we are falling down on the job. This is actually a real emergency.”
Research has shown that most parents would immunize their children if their pediatrician or family practitioner recommended the HPV vaccine as part of the standard package of vaccines for adolescents (Holman DM et al. JAMA Pediatr. 2014;168[1]:76-82, and Rickert VI et al. Vaccine. 2015;33[5]:642-647). But studies also have found that parents, like physicians, sometimes delay immunization because they think their child is years away from becoming sexually active and contracting HPV. In addition, the HPV vaccine requires 3 trips to the physician’s office, which might prove daunting to busy families.
The urgency for vaccination is underscored by the fact that HPV is the most common sexually transmitted infection, and most sexually active men and women become infected at least once during their life (http://1.usa.gov/1NZJvwU). Moreover, persistent infection with certain strains causes virtually all cervical cancers as well as about two-thirds of vulvar and penile cancers, three-fourths of vaginal and oropharyngeal cancers, and about 9 in 10 anal cancers (http://1.usa.gov/1CjY7nN).
Human papillomavirus vaccines can’t prevent infection after the fact, which is why the ACIP recommends immunization for preteens before they become sexually active. The ACIP has recommended routine vaccination of girls aged 11 or 12 years since 2006, when Gardasil, the first approved HPV vaccine, became available (http://1.usa.gov/1DoEGKj). The committee issued the same recommendation for boys in 2011 (http://1.usa.gov/1G97qVc).
Gardasil, Merck’s quadrivalent vaccine approved for males and females, protects against 2 HPV types (16 and 18) that cause 70% of cervical cancers as well as 2 other HPV types (6 and 11) responsible for 90% of genital warts cases. Cervarix, GlaxoSmithKline’s bivalent vaccine approved only for girls, protects against the same 2 cancer-causing types of HPV (http://bit.ly/1wPTsYd). In December, the Food and Drug Administration approved the 9-valent HPV vaccine (9vHPV), Gardasil 9, which protects against HPV types in the original quadrivalent vaccine and an additional 5 HPV types that cause cervical cancers (http://1.usa.gov/1LiJp4E). ACIP recently updated its HPV vaccine recommendations to include 9vHPV as one of the three recommended vaccines that can be used for routine immunization (Petrosky E et al.MMWR Morb Mortal Wkly Rep. 2015; 64[11]:300-304).
Human papillomavirus types 16 and 18, associated with cervical cancer, are also associated with penile and oropharyngeal cancer. Although the HPV vaccines are presumed to protect against those 2 cancers as well as cervical cancer, clinical trials have not yet been conducted to demonstrate efficacy against these cancers (http://1.usa.gov/18tjZiY). Such studies would be prohibitively long and expensive, Willoughby said, because researchers have nothing comparable to the Pap smear to detect precancerous penile or oropharyngeal lesions.
Despite the preventive benefits and documented efficacy in protecting against cervical cancer, HPV vaccination rates remain far below 2 other recommended preteen vaccines—the one for Tdap (against tetanus, diphtheria, and pertussis) and the meningococcal conjugate vaccine (Elam-Evans LD et al. MMWR Morb Mortal Wkly Rep. 2014;63[29]:625-633). In 2013, 86% of US teens aged 13 to 17 years had received Tdap and 77.8% had received the meningococcal vaccine. But only 57.3% of girls and 34.6% of boys had received at least 1 of the 3 recommended doses of HPV vaccine, and only 37.6% of girls had received all 3 doses (http://kff.org/womens-health-policy/fact-sheet/the-hpv-vaccine-access-and-use-in/).
These vaccination rates fall far short of the Healthy People 2020 initiative’s target goal to have 80% of 13- to 15-year-old girls and boys fully immunized with all 3 HPV doses (http://1.usa.gov/1MFXTH7).
“Many people, like me, thought that a vaccine to prevent cancer would be a no-brainer,” Anne Schuchat, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said in an interview.
The low immunization rates indicate that has not been the case, Schuchat said. “I do think providers think they’re recommending the vaccine, but the way they’re talking about it is often different and may raise questions instead of reassure,” she said. In a recent editorial, Schuchat noted that if teenagers were offered and accepted HPV vaccination every time they received another vaccine, first-dose coverage for HPV would exceed 90% (Schuchat A. N Engl J Med. 2015;372[8]:775-776). However, she wrote, “research suggests that parents hear mixed messages about HPV vaccination; pediatricians communicate less urgency and give weaker recommendations for this vaccine.”
The lack of state mandates also may help explain the lower HPV immunization rates. All but 4 states require Tdap and 22 states and Washington, DC, require the meningococcal vaccine for all middle school–aged children (2 other states require the meningococcal vaccine only for boarding school students), according to the Immunization Action Coalition (http://bit.ly/1CnGROp and http://bit.ly/1Cm9XMv). But only Washington, DC; Virginia; and Rhode Island have laws requiring the HPV vaccine for middle school children, according to the coalition (http://bit.ly/19s1MU1)
WHAT’S SEX HAVE TO DO WITH IT?
Physicians’ hesitancy to recommend the HPV vaccine dates back to its introduction, said pediatrician Julie Morita, MD, acting commissioner of the Chicago Department of Public Health. “Right after it was recommended by the ACIP… there was this immediate backlash about it being this STD [sexually transmitted disease] vaccine. Providers had this discomfort,” Morita said.
Pediatricians tend to regard the HPV vaccine as a different breed from the other preteen vaccines because the virus is sexually transmitted, and some of them aren’t comfortable talking about sexual health, said pediatrician Kristen Feemster, MD, a faculty member at PolicyLab at the Children’s Hospital of Philadelphia and an infectious disease specialist.
Such attitudes could in part explain low vaccination rates, suggests psychologist Gregory Zimet, PhD, co-director of the Center for HPV Research at Indiana University–Purdue University Indianapolis. He echoed Feemster, saying, “It [the HPV vaccine] is typically brought up last and discussed in a way like it’s almost a different species of vaccine, which reinforces [the notion] that there’s something weird about it,” he said. “It unfortunately reveals the social stigma that’s so pervasive around sex and sexually transmitted diseases.”
Pediatricians also assume parents will be reluctant to discuss or consider vaccination because HPV is sexually transmitted. Physicians hesitate to bring it up because they still expect a negative reaction, said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University. As a result, instead of giving parents a chance to ask questions, they’ll say, “we can wait until next year,” said Debbie Saslow, PhD, director of breast and gynecologic cancer at the American Cancer Society. “They’re afraid that the parent is going to ask about sex,” she said.
Parents and physicians might worry that adolescents will view immunization against HPV as a greenlight for unsafe sexual activity, Emory epidemiologist Robert A. Bednarczyk, PhD, wrote in a recent commentary (Bednarczyk RA. JAMA Intern Med.doi:10.1001/jamainternmed.2014.7894 [published online February 9, 2015]). But research has disproved that notion. For example, an analysis of a large, longitudinal insurance database of girls aged 12 to 18 years found that HPV vaccination was not associated with increases in sexually transmitted infections, “suggesting that vaccination is unlikely to promote unsafe sexual activity” (Jena AB et al. JAMA Intern Med. doi:10.1001/jamainternmed.2014.7886 [published online February 9, 2015]).
Increasingly, parents seem to be less focused on a possible link between the HPV vaccine and increased sexual activity. Zimet and his colleagues have shown that sexual promiscuity ranked lowest among parents’ reasons for not having vaccinated their son (Donahue KL. Vaccine. 2014;32[31]:3883-3885). In the study, they surveyed a national sample of parents of 11- to 17-year-old boys who had not received the HPV vaccine. Among 9 possible reasons for nonvaccination, only 8.5% of the parents said they thought the shot would make it easier for their son to have sex. Some 15% said they considered the HPV vaccine potentially dangerous, and 17.7% said they felt the vaccine could have adverse effects. But a whopping 60.9% said their doctor or health care provider had not recommended the vaccine.
A recent study involving parents or guardians of 11- to 17-year-old girls who had not been vaccinated and their physicians similarly found that one of the most common reasons parents reported for nonvaccination was the lack of physician recommendation (Perkins RB. Pediatrics. 2014;134[3]:e666-e674). The study also revealed that some providers delayed recommending the vaccine for girls perceived to be at low risk for sexual activity.
“If you ask physicians, they’ll say they recommend it. That doesn’t really capture what’s going on. We hear providers essentially talking parents out of vaccinating,” Zimet said in an interview.
Although social stigma and discomfort surrounding STDs and sexual health may deter productive conversations between physicians and parents about the HPV vaccine, even when framed as a cancer vaccine, it “is a harder sell for some pediatricians and some parents because the consequences are 20 years down the road,” Willoughby acknowledged.
The HPV vaccine is unique among the 3 preteen vaccines in that it requires 3 doses—administered over a period of 6 months—instead of a single dose.
Other countries are addressing potential adherence issues that might contribute to low immunization rates by moving toward a 2-dose regimen for younger teens and preteens. In 2014, the World Health Organization (WHO) changed its HPV vaccination recommendations to a 2-dose schedule, at least 6 months apart, if the first dose is administered before age 15 years (WHO Report. Vaccine.doi:10.1016/j.vaccine.2014.12.002 [published online December 12, 2014]). Based on the WHO recommendation, the European Medicines Agency last year approved that regimen for quadrivalent and bivalent HPV vaccines for adolescents 9 to 13 or 14 years old (http://bit.ly/1MEA7LK and http://bit.ly/1GdDt6p). And in February, Canada’s National Advisory Committee on Immunization began recommending 2 doses, 6 to 12 months apart, for children aged 9 to 14 years (http://bit.ly/1CktDAw).
In the United States, the ACIP wanted to wait until the Food and Drug Administration approved Gardasil 9 before it considered an across-the-board reduction in the number of doses needed, Schuchat said. After the December approval, Merck began shipping Gardasil 9 in February, and the ACIP has added the vaccine to its recommendations for routine vaccination of 11- and 12-year-old boys and girls, according to company spokeswoman Pamela Eisele.
Merck is now conducting a study of alternative schedules and timing for administering the vaccine, Schuchat said. “I think that over the next year and a half, there should be new data about whether potentially 2 doses in some age groups would be okay with the 9-valent,” she said.
Making HPV vaccination available in venues other than the physician’s office would help accelerate uptake, the President’s Cancer Panel wrote in its 2012-2013 annual report (http://1.usa.gov/1bqAspO). Pharmacies are a particularly promising location, but in 2012, pharmacists in more than a third of states were not permitted to administer HPV vaccine to 12-year-old girls, according to the report. In more than half the states, pharmacists were allowed to do so—depending on the state—if they entered into a supervision agreement with a prescriber or if the girl had a prescription. Only a few states allowed pharmacists to administer HPV vaccines to 12-year-old girls with no prior approval.
LESS IS MORE
It may seem counterintuitive, but perhaps the best way to raise HPV immunization rates is to focus less, not more, attention on the vaccine, experts suggested.
That’s the objective of the “Less Is More” campaign developed by Morita and Rachel Caskey, MD, MaPP, assistant professor of pediatrics and general internal medicine at the University of Illinois College of Medicine. As its name suggests, the campaign aims to persuade physicians to stop overexplaining the HPV vaccine and instead treat it in the same informative and casual manner that they do other adolescent and childhood vaccines (http://bit.ly/1CnTEAn).
Launched in 2012, Less Is More encourages physicians to allow parents to initiate the conversation. The campaign has reached out to Chicago providers in presentations at several venues around the city, covering such topics as the need to strongly recommend the HPV vaccine and information about its safety and effectiveness.
“I feel the vast majority of our practitioners now get it,” Morita said, adding that the Less Is More message is spreading to their peers around the country.
Vaccine advocates hope the word spreads quickly, boosting HPV immunization rates among preteens and teens. “Every year we don’t turn things around, more people are unprotected and more HPV infections will occur,” Schuchat said.
