CDC, FDA Study Reinforces Safety, Efficacy of Gardasil

After a joint review of more than 12,000 adverse events reported after administration of quadrivalent human papillomavirus, or HPV, vaccine, FDA and CDC researchers concluded the vaccine "continues to be safe and effective, and its benefits continue to outweigh the risks."

Researchers from the agencies published their findings in the Aug. 19 Journal of the American Medical Association, or JAMA.

The vaccine, which is manufactured by Merck & Co. Inc. and sold as Gardasil, is recommended for teens ages 11-18 (2-page PDF; About PDFs) and young women ages 19-26. (2-page PDF; About PDFs) Since its licensure in 2006, more than 23 million doses of Gardasil had been distributed as of Dec. 31, 2008.

After reviewing all 12,424 reports of adverse events after HPV immunization made to the joint CDC-FDA Vaccine Adverse Events Reporting system from June 2006 through December 2008, researchers from the two agencies reported that, generally, adverse event rates were similar to what is seen in safety reviews of other vaccines. However, they did acknowledge the presence of "disproportional reporting" of syncope (8.2 per 100,000 doses) and blood clots (0.2 per 100,000), compared with that seen with administration of other vaccines.

"My view is that the data in the article indicate that the vaccine is very safe," said Doug Campos-Outcalt, M.D., M.P.A., the AAFP's liaison to the CDC's Advisory Committee on Immunization Practices, or ACIP, and associate head of the department of family and community medicine at the University of Arizona College of Medicine, Phoenix. "At the very minimum, the vaccine protects against precancerous cervical lesions and genital warts.

"This is a very significant outcome -- with the associated morbidity and medical procedures prevented."

The vast majority of adverse events reported after vaccine administration (94 percent) were not classified as serious. The most common events reported were syncope, pain and redness at the injection site, dizziness, nausea, and headache.

Six percent of adverse events were regarded as serious, including 32 deaths. The agencies said, however, that no common pattern suggested the deaths were caused by the vaccine. In cases where autopsy results, medical records or death certificates were available, the cause of death often could be attributed to other factors, such as diabetes, viral illness, drug use and heart failure.

The researchers reiterated the need for physicians to observe the recommended 15-minute postvaccination waiting period. Of the more than 1,800 reports of fainting immediately following vaccination, 293 instances resulted in falls, of which 200 resulted in head injuries.

In addition to the CDC-FDA report, the Aug. 19 issue of JAMA features two other items that discuss the HPV vaccine and its manufacturer.

In an editorial, Charlotte Haug, M.D., Ph.D., MSc., editor of the Journal of the Norwegian Medical Association, writes that it is difficult to assess the risks and benefits of the relatively new vaccine because the benefits still are uncertain. And an article by Sheila Rothman, Ph.D., and David Rothman, Ph.D., acknowledges the benefits of the vaccine but is critical of Merck's marketing of the drug and the involvement of professional medical organizations in promoting the product.

Merck disagreed with Haug's assertion, saying in an Aug. 20 news release that 50 years after the advent of Pap testing, 30 women are diagnosed with cervical cancer every day in the United States.

"Now that there is a vaccine, we have an opportunity to not only impact this disease through early detection but also through a medical intervention," Richard Haupt, M.D., M.P.H., head of Merck's Gardasil clinical program, said in the release.

The manufacturer also said that it, the CDC and the FDA will continue conducting postmarketing safety surveillance.