The approval of Gardasil, a vaccine that protects against four strains of human papillomavirus (HPV), has sparked a nationwide controversy. Gardasil is the first vaccine that may actually prevent cancer, but its efficacy and public health implications have been overshadowed by the debate over whether the vaccine should be required for school attendance. (A second vaccine, Cervarix, has not yet been approved but has shown comparable efficacy.)

In June 2006 the Food and Drug Administration licensed Gardasil for use in females ages nine to 26 years. The recombinant vaccine is designed to prevent cervical cancer, precancerous cervical dysplasia, genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices and the American Academy of Pediatrics (AAP) have recommended routine vaccination of girls ages 11 and 12.

Figure. Liz Ruscitti, a nurse from Cedar Park, Texas, poses with her 12-year-old daughter Amanda. Ruscitti agrees with the recommendation that all 11- and 12-year-old girls should receive the Gardasil vaccine, which protects against the types of HPV responsible for most cervical cancers. Ruscitti told the Associated Press that she has had cervical cancer caused by HPV. "There's gonna be people that aren't gonna be aware and they won't be aware unless the state puts it on the list of mandated shots," she said. Associated Press/Harry Cabluck

Gardasil was approved based on the results of four clinical trials averaging three years in length and involving 21,000 women ages 16 to 26. The studies, published in the May 10 issue of the New England Journal of Medicine, showed that in women not previously exposed to HPV, the vaccine was close to 100% effective in preventing precancerous lesions of the cervix, vagina, and vulva, as well as anogenital warts. Questions remain about Gardasil's overall effectiveness, the duration of its protection, and possible long-term adverse effects. In addition, aggressive lobbying by the vaccine's manufacturer, Merck, to convince state legislatures to make the vaccine mandatory for prepubescent girls has drawn intense criticism from some parent organizations and medical groups.

"The rush to mandate vaccination is enigmatic," says George Sawaya, MD, of the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco. "Making national recommendations, in my view, is also premature, since the studies are not yet completed. These early results are encouraging, but we shouldn't let enthusiasm circumvent the usual scientific, evidence-based process for making guidelines, recommendations, and mandates." He adds, "I think it's difficult to discuss mandates when the current trials are ongoing. What we have seen so far are interim analyses."

Texas became the first state to mandate the vaccine in February, when Governor Rick Perry issued an executive order requiring vaccination for girls entering the sixth grade. The executive order allowed Perry to circumvent strong opposition in the state legislature stemming from concerns of parents' groups and others that the mandate would promote premarital sex and state control over raising children. It was reported that Merck had contributed to Perry's reelection campaign and that current and former members of Perry's staff have ties to Merck lobbyists in Texas. The state legislature eventually rescinded the order by a vote of 181 to three. Merck was also said to be funding lobbyists working for similar mandates in at least some of the more than 20 other states that were considering them. The company has since stopped funding lobbying on the issue.

Critics of the mandates question the notion that widespread vaccination is needed, given that HPV, which is primarily sexually transmitted, is not spread by casual contact. Mandates are usually considered when an infection requires herd immunity, explains Joseph Bocchini, Jr., MD, FAAP, of the Department of Pediatrics at Louisiana State University Health Sciences Campus, Shreveport, and chairman of the AAP's Committee on Infectious Diseases. "Moral concerns have become prominent and centered around the mandate," says Bocchini. "The whole process was moving along smoothly, and it was the issue of mandating the vaccine that created controversy."

Although organizations such as Focus on the Family and the Christian Medical Association don't believe that the vaccine should be mandatory, they strongly support the vaccine itself, says Erin Cruise, MSN, RN, NCSN, an instructor at Radford University School of Nursing in Virginia and a school and public health nurse. The groups prefer to let HPV vaccination be a parental decision.

Polls indicate that a majority of parents do not feel that HPV vaccination should be mandated. The University of Michigan C. S. Mott Children's Hospital National Poll on Children's Health, conducted online in March and weighted to reflect the U.S. population, revealed that only 44% of parents favored a mandate for the HPV vaccine.

It's unfortunate that the focus has been on the mandate rather than on the vaccine itself, says Bocchini. "The focus ought to be on the acceptance, on parents knowing that HPV is the main cause of cervical cancer."

According to the CDC, HPV infects an estimated 6.2 million Americans every year and is the most common sexually transmitted disease. However, the prevalence of types 16 and 18-detected in 99% of cervical cancers-is relatively low and accounts for only 3.4% of all HPV infections, according to a report published in the February 28 issue of the Journal of the American Medical Association. Not all patients infected with these high-risk types will develop cervical cancer, and 90% of HPV infections resolve within two years.

The price of the vaccine is steep, at an estimated $360 for the series of three shots, plus the associated costs of three visits to a clinician's office. That, Cruise points out, is one reason for a mandate, because "vaccines mandated for public school entry are usually covered by state funds or insurance."

And the prevalence of HPV infection results in significant resources being devoted to managing the lesions that accompany the virus, placing a substantial burden on the health care system, Bocchini says. "These lesions can go on to develop into cervical cancer. Even though the rate of cervical cancer had declined dramatically in the United States, thanks to the availability of Papanicolaou tests, the disease still causes significant morbidity and mortality."

Mandatory immunization may also protect children who are sexually abused, says Cruise. "An article in the October 2006 issue of the Journal of School Nursing stated that nearly 30% of adolescent girls report having been forced or pressured to have sex. A report from the surgeon general in 2001 indicated that 22% of girls and women have been victims of a forced sexual act, and 104,000 children are victims of sexual abuse each year. These children are not using free will to decide whether they'll be exposed to sexually transmitted infections and HPV."

Studies are currently examining the vaccine's efficacy in boys and sexually active men. "Once we have those data," says Bocchini, "it can help us decide whether vaccinating boys is appropriate, and whether it can help control the spread of the virus."

And according to one of the studies published in the May 10 issue of the New England Journal of Medicine, there is also an association between HPV and oropharyngeal cancer, strengthening the case for vaccination.

Roxanne Nelson, BSN, RN