09.14.11

HPV Vaccine's Tricky Ethics

Rick Perry may have been wrong to try forcing HPV vaccinations in Texas, and Michele Bachmann was definitely wrong when she said HPV causes mental retardation, but the issue of mandating vaccinations can be ethically tricky, Sharon Begley explains.

For a pretty good vaccine, the inoculation against human papillomavirus (HPV)—which causes almost all cases of cervical cancer—has been extremely ill served by almost everyone concerned, from its manufacturer to politicians who have tried (rarely successfully) to make it mandatory for school-age girls. Now that it has become an issue among the Republican presidential hopefuls, the HPV vaccine is getting vilified as unfairly as, say, end-of-life counseling (death panels!), which has advocates for women’s health, pediatricians, and cancer experts worried that the potentially lifesaving vaccines will be undermined by politics.

The current tempest arose from the fact that Texas Gov. Rick Perry issued an executive order in February 2007 requiring that all girls entering sixth grade receive the cervical cancer vaccine, for which Merck had won Food and Drug Administration approval in 2006, unless their parents objected (by submitting a form that is also used to opt out of measles, mumps, and other childhood vaccines). Arguing that the policy could “significantly reduce cases of cervical cancer and mitigate future medical costs,” Perry defended it against charges that he was allowing the government to encroach on parental authority, saying he was “firmly on the side of protecting life.” (Cervical cancer will kill an estimated 4,000 women in the U.S. this year.) The following May, the Texas Legislature overturned the order, which never went into effect. Since he entered the presidential race, Perry has waffled, justifying his action as a way to save lives and dollars but saying he should have had “a conversation with the citizenry” first and let parents opt in rather than opt out.

That has not been enough for his opponents, who have slammed him for inserting the government into girls’ and their parents’ medical decisions (ignoring the fact that every state requires some vaccines for school, though parents can opt out for religious or “philosophical” reasons). Rep. Michele Bachmann went further, saying the HPV vaccine causes mental retardation.

The facts are otherwise. First, the basics. There are two FDA-approved HPV vaccines. Gardasil got the OK for use in girls and young women ages 9 through 26 for the prevention of cervical, vulvar, vaginal, and anal cancers caused by two forms of HPV, called types 16 and 18. It also prevents genital warts caused by HPV strains 6 and 11, and in 2009 was FDA-approved for that purpose in males as well. Strains 16 and 18 cause 70 percent of cervical cancers, while 6 and 11 cause 90 percent of the cases of genital warts. These four strains also cause the benign cervical changes that result in abnormal Pap tests. The FDA approved a second vaccine, Cervarix, from GlaxoSmithKline, against cervical cancer (but not genital warts) in October 2009, for girls and women ages 10 to 25. The U.S. Centers for Disease Control and Prevention recommends HPV vaccination of girls at age 11 or 12, and “catch-up vaccination” for those 13 through 26. The vaccines, which consist of series of three intramuscular shots given over six months, are 97 to 100 percent effective in preventing HPV infection.

Age 11 may seem early to get a vaccine against a virus that can be acquired only through sexual activity. (The CDC estimates that 20 million American men and women ages 14 to 59 are infected with at least one type of HPV, including more than 25 percent of women 14 to 59.) The early age reflects the fact that the vaccines prevent HPV infection only if you have not been exposed to the virus, explains pediatrician and infectious-disease expert Joseph Bocchini of Louisiana State University, so the inoculation is most likely to be effective before a girl is sexually active. “We don’t know why that is,” he says. “The vaccine causes you to develop a strong antibody response to the virus, so that if you are subsequently exposed you do not become infected. But if you are already infected, the vaccine does not change the course or outcome of the infection.” Some 70 percent of females will be infected with HPV within five years of becoming sexually active. On the other hand, if you are not sexually active and were never exposed to HPV, the vaccine should work at any age.

The question of whether the vaccines should be mandated is where things get messy, but not in the way you might expect: public-health experts largely oppose requiring them for, say, school. The American Academy of Pediatrics has recommended the vaccine since 2007, but opposes making it mandatory. Cervical cancer “is severe enough and common enough that the benefits of the vaccine clearly outweigh the risks,” says LSU’s Bocchini, who served on AAP’s vaccine committee. But efforts like Perry’s in 2007 “to mandate it were premature.”

That’s because the vaccine was, and still is, relatively new. Its long-term safety and effectiveness in the general population is therefore unknown: whenever a drug or vaccine is approved, there is always the possibility that people in the clinical trials that found it to be safe and effective might be different from those who take it post–FDA approval, and therefore have more adverse side effects or benefit less from it. “There needs to be more experience with the vaccines in the general population,” says Bocchini. “Mandates are something you do after there has been years of experience with a vaccine, in particular so you can see whether there are rare side effects that did not show up in the clinical trials.”

The need for caution was made clear in a report on the adverse effects of vaccines by the Institute of Medicine, released last month. Its chapter on HPV vaccines examines 13 kinds of reported problems, from multiple sclerosis to Guillain-Barre syndrome. In 12 cases it found the evidence “inadequate” to link the vaccine to the illness, mostly because only anecdotes and not rigorous research suggest a connection. Only anaphylaxis—an extreme allergic reaction—seems to be caused by the vaccine in a small percentage of cases, which reflects the fact that some people are allergic to some components of all vaccines. As for mental retardation, this week the American Academy of Pediatrics weighed in: AAP “would like to correct false statements made in the Republican presidential campaign that HPV vaccine is dangerous and can cause mental retardation,” it said in a statement. “There is absolutely no scientific validity to this statement. Since the vaccine has been introduced, more than 35 million doses have been administered, and it has an excellent safety record.”

The vaccine is still relatively new. Its long-term safety and effectiveness in the general population is therefore unknown.

Merck launched an intense and controversial “education” campaign to promote Gardasil, and in September 2006 the Michigan Legislature became the first to propose requiring the vaccination for girls in public schools. The bill did not become law, and today, although other states made similar attempts, only Virginia (as of 2008) and the District of Columbia (2007) require the vaccine (but only for girls). After catching flak for its lobbying efforts, Merck “suspended our state-level lobbying for a school requirement in 2007,” says a spokesperson.

In addition to the medical reasons to oppose making HPV vaccines mandatory, there are ethical ones that have nothing to do with the “keep your government out of my health care” ideology. Instead, the concerns reflect the fact that unlike measles or diphtheria or rubella, HPV is not spread by casual contact. You can be exposed only through sex, which means abstinence is an equally effective preventive. “In general, you use coercion in public health to prevent imminent harm to others,” James Colgrove, a professor of sociomedical sciences at Columbia University’s Mailman School of Public Health, told the British medical journal The Lancet in 2007. “You don’t pass a law requiring something unless [failing to do so] causes an imminent harm.” An early ethical issue—and one that was front and center when Perry issued his executive order—is that the original mandates, including Perry’s, applied only to girls, since Gardasil had not been approved for males. “It’s a policy that would keep girls out of school and not boys,” AAP’s then-president-elect Renee Jenkins told The Lancet.

The other ethical issue that argues against an HPV-vaccine mandate has to do with the available alternatives. For one thing, in 80 to 90 percent of cases, HPV infection goes away on its own, says Bocchini, “and without causing a problem.” On average, the immune system clears the virus in four to 20 months. But when it does cause a problem—cervical cancer—it can be dangerous or fatal. About 50 million to 60 million Pap tests are done each year in the U.S.; about 7 percent are abnormal. The Pap test is unsurpassed when it comes to early detection of cancer, which has led some vaccine critics to argue that it’s all that’s needed to prevent cervical cancer. There are two problems with that argument. The most obvious is that the Pap test does not prevent cancer; at best, it detects malignant and pre-malignant cells before they become life-threatening. Treating the malignancy can require surgery. The other problem is that not every woman has a Pap test as often as she should—which is why there are some 12,000 new cases of cervical cancer in the U.S. every year. That is reason enough to let the vaccine prove its merits rather than inciting a backlash by requiring anyone to get it.