Doctors were blown away a few years ago when the New England Journal of Medicine published the first results of Merck's trials for a vaccine that protects against the human papillomavirus. The vaccine had prevented all infections caused by two deadly strains of the virus responsible for most of the world's 270,000 annual cervical cancer deaths. This was an unheard-of result. But as safe and effective as it appears to be, the vaccine—which the Food and Drug Administration approved today—will probably take years to have an impact on cervical cancer.
If you've had sex, you've probably been infected with the human papillomavirus, the only cause of cervical cancer. Fortunately, HPV infections usually clear up on their own, only 15 percent of the viral strains are carcinogenic, and doctors can halt slow-growing precancerous growths through routine cervical exams. Most of the 14,000 cases of cervical cancer in 2004 in the United States occurred in women who hadn't had a pap smear in three years or more. If all women were screened regularly, we wouldn't need a vaccine.
In Merck's trials involving about 20,000 girls and young women, the HPV vaccine eliminated all major cervical infections caused by the two strains of the human papillomavirus that cause 70 percent of cervical cancers. Merck is using a version of a vaccine, developed at the National Cancer Institute, which was cloned in viruses grown in a caterpillar-cell culture. It also seems to prevent vaginal cancers caused by these highly carcinogenic viruses and prevents genital warts caused by HPV 11 and HPV 6, two other strains contained in the vaccine.
But the vaccine doesn't reverse existing infections and doesn't seem to protect against the strains that account for the remaining 30 percent of cervical cancer cases. Sexually active, vaccinated women will continue to get pap smears that show abnormalities and have to be investigated. "It is important not to set false expectations that the need for pap smears is ending," says Jessica Kahn, a University of Cincinnati pediatrician who worked on the vaccine's clinical trials. Because it can take decades for HPV infections to progress to cancer, it may take that long to measure the benefits of the vaccine.
The vaccine's cost also has raised some questions about its value. If every American girl gets one course of three shots, which is expected to cost $300 to $500 total, then the national health-care bill could be in the range of $1.5 billion, on top of the $5 billion already spent on cervical cancer prevention. Many existing vaccines cost roughly a tenth of that retail. And the government, which provides more than half of all childhood vaccines, buys them even cheaper. The Centers for Disease Control's plan is to vaccinate 10-to-12-year-old girls, who are already supposed to go to the pediatrician between those ages for a meningitis shot and a pertussis-diphtheria-tetanus booster. (It's vital that girls be vaccinated before they have sex for the first time, since each new sexual encounter brings a 15 percent chance of HPV infection.) The Merck vaccine produces a strong immune response, but will it last from girlhood through a woman's sexual life? No one knows.
Another problem is how to get the vaccine to the women and girls who need it most—poor, uneducated women and those in the developing world. "None of us are going to be happy if the only women who get the vaccine are the same women who are already getting regular screens for cervical cancer," John Schiller, one of the vaccine's inventors, told me at his National Institutes of Health laboratory. The Vaccines for Children program, a Clinton-era entitlement, will probably make the vaccine available for free to poor children in the United States. But social conservatives like Focus on the Family leader James Dobson have opposed making vaccination mandatory, believing vaccination might lower barriers to teen sex.
In a roundabout way, this prudery may keep the vaccine out of reach of poor girls. Research and experience have shown that only mandatory-vaccination laws—which typically increase vaccination rates by 10 to 15 percent—get even cheap vaccines to the poor. Given the politics, state legislatures and public health boards may shy from requiring HPV vaccine for middle-school entry. Even mainline medical ethicists like Richard Zimmerman of the University of Pittsburgh have argued that "it seems unreasonable to mandate that an adolescent or college student who plans lifelong abstinence for religious or other reasons be vaccinated."
The answer may be to require HPV vaccination for children while explicitly allowing parents with strong beliefs to exempt their kids. This would recognize that mandatory vaccination campaigns work not by dragging refuseniks kicking and screaming to the medical clinic, but by forcing the issue for people who have to take the bus or borrow a ride to get to the doctor. Most states already allow some kind of religious or philosophical exemption for those who oppose other vaccines for their children.
Eventually, boys—who are equally responsible for spreading HPV—will need to get the vaccine, too, though they suffer rarely from penile and anal cancers caused by it. The history of vaccination campaigns against rubella, a normally trivial virus that devastates first-trimester fetuses when it infects their mothers, showed that the best way to eliminate a virus is to kill it in both sexes. This will add to the cost. Along with Merck, however, GlaxoSmithKline hopes to license a human papilloma vaccine, with approval slated for January. Schiller hopes that eventually the two firms' competition will lower prices and that the companies will engage in a beneficial "arms race," adding protection fromadditional lethal strains of HPV as they battle for market share. At the same time, Schiller is helping two Indian companies make cheaper versions of the vaccine for developing countries.
In the end, the HPV vaccine should prove a worthy addition to the cause of fighting cancer. So, it will be worth it to suck up the cost—and be patient about seeing results.