EXPERT PANEL The new HPV vaccine: What the ObGyn needs to know
Who should be immunized? Who pays? Should women over 26 be vaccinated? Is cervical screening on its way out?
IN THIS ARTICLE
OUR EXPERT PANELISTS
What once seemed far in the future is now a reality: the human papillomavirus (HPV) vaccine. The quadrivalent vaccine (Gardasil) that prevents the development of lesions caused by HPV types 6, 11, 16, and 18 was approved last June by the US Food and Drug Administration (FDA) for clinical use in females 9 to 26 years old. Shortly after its approval, the Advisory Committee on Immunization Practices (ACIP) issued guidelines on who should be vaccinated.
In light of these developments, OBG Management invited Dr. Tom Wright to convene an expert panel to discuss the ACIP recommendations and ways of introducing the vaccine into practice.
“Vaccination can reduce the disease burden—even in a woman who has had multiple sexual partners”—Barbara S. Levy, MD
“Both the ACIP and ACOG suggest that we encourage ‘catch-up’ vaccination of sexually active women through 26 years”—Thomas C. Wright, MD
“Young people should not have to sneak around to get protection”—Mark DeFrancesco, MD, MBA
“The HPV vaccine is an ObGyn vaccine, and we should embrace it with vigor”—Stanley Gall, MD
“Even if we reach all at-risk young women with our vaccine program, they will still be at risk for infection with other high-risk HPV types”—Barbara S. Levy, MD
ACIP recommends vaccination at age 11 or 12
WRIGHT: Dr. DeFrancesco, would you review the ACIP recommendations for us?
DeFRANCESCO: Shortly after the FDA approved Gardasil, the quadrivalent vaccine (Merck, Whitehouse Station, NJ), the ACIP recommended routine vaccination with 3 doses for girls aged 11 or 12 years, but noted that vaccination is also acceptable for girls as young as 9 at the discretion of the physician or health-care provider. The new 2006–2007 Recommended Adult Immunization Schedule states that the HPV vaccine is “recommended for all women aged ≤26 years of age” (available at www.cdc.gov/nip/recs/adult-schedule).
Ideally, the vaccine should be given before the onset of sexual activity (ie, before a woman is exposed to the virus), but sexually active girls and women through 26 years should still be vaccinated, as they are not likely to have been exposed to all 4 HPV types covered by the vaccine.
ACOG recommendations mirror those of ACIP
WRIGHT: Dr. Gall, are ACOG’s recommendations similar to the ACIP’s?
GALL: Yes. They mirror those of the ACIP, as they recommend that:
Should sexually active women be vaccinated?
WRIGHT: Both the ACIP and ACOG suggest that we encourage “catch-up” vaccination of sexually active women through 26 years. However, many experts disagree, arguing that vaccination of this population may not be worth the effort.
Dr. Gall, why does ACOG recommend that sexually active women get vaccinated?
GALL: Data from the Merck Phase III trials indicate that only 25% of women at age 23 are either serologically or DNA positive for 1 of the 4 HPV types included in the quadrivalent vaccine and that only 0.1% of women are positive for all 4 vaccine HPV types. Data on HPV 16 from the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), are in line with this estimate. It is pretty clear that most sexually active women aged 26 or younger will benefit from vaccination.
Vaccine may benefit even women with high-risk sexual practices
WRIGHT: OK, Dr. Levy, you heard Dr. Gall say we should vaccinate sexually active women. Are you convinced? What are you going to tell a 24-year-old single woman who has had 12 lifetime sexual partners?
LEVY: I would tell her that she is extremely likely to have been infected with 1 or more HPV strains—but unlikely to have been exposed to all 4 types present in the vaccine. I would also explain that the vaccine is almost 100% effective at preventing genital warts caused by HPV 6 and 11 and will prevent both infections and lesions with HPV types 16 and/or 18 if the patient has not been exposed to them.
The benefit for this 24-year-old may not be as great as it is for our primary target population of preteens not yet exposed to HPV, but vaccination can reduce the disease burden—even in a woman who has had multiple sexual partners.
If this patient has already had genital warts and an abnormal Pap smear, or is positive for high-risk HPV DNA, the benefit would be even lower. Ultimately, she will have to decide whether the cost is worth the lessened benefit in her situation.
Lessons learned from the hepatitis B experience
WRIGHT: One of the things we learned 20 years ago when we introduced the hepatitis B vaccine is that limiting vaccination to groups expected to gain the most benefit doesn’t work very well. With hepatitis B, we initially targeted only high-risk groups such as intravenous drug users, men who have sex with men, and health-care workers—but this strategy didn’t reduce the rate of hepatitis to the extent expected. Once we recommended universal vaccination of the general population, however, a rapid reduction in hepatitis B occurred.
In many respects HPV is like hepatitis B. I have heard some experts say that we may eventually vaccinate all at-risk women—essentially, all sexually active women.
WRIGHT: Women older than 26 are already asking whether they should be vaccinated. What do we know about the safety and efficacy of the vaccine in these women?
GALL: Even though the number of women infected with at least 1 HPV type, or who have evidence of such infection, exceeds 60% by age 50, only a small number of women will have been exposed to all 4 HPV types covered by the vaccine. Thus, it seems likely that sexually active women over age 26 will benefit from vaccination.
The safety data on the vaccine are excellent. In our experience, the quadrivalent vaccine has been less reactogenic than the influenza vaccine. There is no reason to suspect that the HPV vaccine will be less safe in women over age 26.
Recently, immunogenicity data for the bivalent vaccine—not yet approved by the FDA—were presented to the American Society of Clinical Oncology for women aged 26 to 55 years, and excellent immune responses were observed. All we need to recommend vaccination of sexually active women over age 26 is the efficacy data, and I see no reason to think that the HPV vaccine will not be effective.
Counsel older women about off-label use
WRIGHT: What would you tell a recently divorced 32-year-old who got married in college, has had only a couple of partners, and is beginning to date again?
DeFRANCESCO: The vaccine is approved and recommended only for females aged 9 to 26, so vaccinating an older woman would be off-label—or “off-recommendation,” as those who specialize in vaccination say.
We also know that the immune system is generally more responsive in younger people, although the immunogenicity data that Dr. Gall just mentioned indicate that the bivalent HPV vaccine is highly immunogenic in older women. I would be hard-pressed to deny the apparent protection of the vaccine to a 32-year-old woman simply because she is over age 26.
However, given the medicolegal climate, I would ensure that informed consent includes a caveat about use of the vaccine in someone outside the approved age range and makes it clear that the patient has acknowledged being informed about the “off-recommendation” use.
Readers will want to know that Phase III trials are now assessing the safety and efficacy of the quadrivalent and bivalent vaccines in women over 26; data should be available in the next couple of years.
WRIGHT: I agree completely. In today’s litigious world, it is vital to counsel women appropriately and obtain informed consent prior to any vaccination. One way to educate the patient about potential benefits and risks is by providing her with a Vaccine Information Sheet, available for download from the CDC’s Web site (www.cdc.gov/nip/publications/VIS/default.htm#hpv).
Can an adolescent give her own consent?
WRIGHT: It has not yet been fully clarified whether a sexually active adolescent can provide consent on her own, or whether a parent must sign the consent form. Most states have laws that allow at least some adolescents to seek reproductive services, as well as screening and treatment for sexually transmitted diseases, without parental notification. However, at several meetings I attended recently, lawyers specializing in the legal rights of adolescents said it remains unclear which of these state laws extend to the HPV vaccine.
DeFRANCESCO: I’ve been told the same thing by our legal advisors. Pending clarification, it is important to emphasize to our patients that the vaccine is a cancer vaccine, not a drug to prevent sexually transmitted infection. The vaccine does not give young people “permission” to have sex, but helps prevent them from ever developing cervical cancer. Young people should not have to sneak around to get this protection.
WRIGHT: One of the really big issues is how we are going to pay for the HPV vaccine, which has a list price of $120 per dose and requires 3 injections. If you add the cost of 3 office visits, that’s almost $500.
LEVY: Most insurance companies in our area have already determined that they will cover the HPV vaccine. Even carriers that are usually slow to make coverage decisions added the HPV vaccine to their list of covered services fairly promptly.
WRIGHT: That’s good news for people who have health insurance. What about women who don’t, or who have high deductibles or carve-outs for “preventive services”?
Patients may be willing to foot the bill
LEVY: I have been discussing the vaccine with eligible women and mothers of young girls for several months. Even before payers stepped up with coverage, no patient was seriously concerned about the cost. Clearly, this will not be true for everyone, but when offered an opportunity to avoid cancer, my patients have been happy to pay for it. In addition, many offices now accept credit cards, which may make it possible for patients to make payments over time.
I think success will depend in large part on how we educate our patients. I frequently discuss preventive care in the context of other things we do in our lives for “maintenance.” For example, none of us would expect our automobile insurance to cover the cost of changing the oil or buying new tires. The HPV vaccine is comparable: The costs incurred now may prevent significant health risks in the near future.
Further, the price of the vaccine series is quite low relative to the potential costs of office visits for follow-up of abnormal Pap smears or treatment of genital warts.
We must stress to our patients that Pap smears aid in the detection of cervical cancer precursors, but the vaccine is an opportunity to prevent cervical cancer.
The poor and uninsured have several alternatives
WRIGHT: In the predominantly Latin American neighborhood where I am located, there are many uninsured who simply cannot afford $500 for the full course of 3 vaccinations. For uninsured children and adolescents, or those on Medicaid up to age 19, the federally funded Vaccines for Children program will cover the cost. However, for women aged 19 and older, vaccinations are considered an “optional” benefit under Medicaid, which means that individual states must decide whether the HPV vaccine will be a covered service.
One bit of good news: Merck plans to provide free vaccines, including the HPV vaccine, to low-income and uninsured adults 19 years and older who visit private clinicians who already provide Merck vaccines. Although the details of this initiative have not been finalized, the program may help individuals in states that decide not to cover the HPV vaccine with Medicaid.
Vaccine appears safe near time of conception
WRIGHT: I have heard varying opinions about the level of risk vaccination poses if a woman becomes pregnant shortly afterward. What do the data show?