• 4/9/2008
  • Atlanta, GA
  • Désirée Lie, MD, MSEd
  • Medscape Today (www.medscape.com)

Quadrivalent human papillomavirus (HPV) vaccine (Gardasil; Merck & Co, Inc; Cervarix; GlaxoSmithKline) seems to be safe in a review of data involving more than 30,000 prelicensure and 12.4 million postlicensure doses of the vaccine, although vasovagal syncope may be a newly identified adverse event.

Senior author John Iskander, MD, MPH, acting director of the Immunization Safety Office, Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues reported these findings here at the International Conference on Emerging Infectious Diseases 2008.

The quadrivalent HPV vaccine, manufactured by Merck, was the first to be approved in the United States. The vaccine is active against HPV types 6, 11, 16, and 18 and is indicated in girls and women aged 9 to 26 years.

The researchers reviewed safety data of the vaccine from clinical trials and the US Vaccine Adverse Event Reporting System (VAERS).

In 7 clinical trials involving approximately 21,500 patients, injection site reactions were reported more frequently with vaccine vs placebo (82.9% vs 73.3%), although comparable rates of serious adverse events and deaths were noted. No deaths among prelicensure vaccine recipients were judged to be caused by the vaccine.

Congenital anomalies were also similar among pregnant women who received either the placebo or vaccine. Among patients vaccinated within 30 days of conception, 5 abnormalities in the vaccine group and none in the placebo group were noted, “but no pattern existed,” the authors write in their abstract.

In the VAERS analysis, which included adverse events reported after licensure, approximately 2500 reports were made from June 2006 to July 2007 after an estimated 12.4 million doses of the vaccine had been distributed in the United States. Of those reports, 149 involved serious adverse events for a rate of 1.9 per 100,000 doses.

Vasovagal syncope was reported in 300 individuals involved in reports to VAERS. According to the researchers, this was a “newly identified” adverse event with the vaccine. Guillain-Barré syndrome was confirmed in 5 vaccinees. Among 3 confirmed deaths, none seemed to be vaccine related.

A pregnancy registry in the United States has been established to monitor pregnancy outcomes in women who have received the vaccine as well as a required phase 4 study. In addition, the Vaccine Safety Datalink is conducting an active surveillance study in a US managed care population. A long-term follow-up study in the Nordic countries, using their vaccination registries, is also underway.

“Our review provides reassuring evidence about the safety of [this vaccine],” Dr. Iskander told Medscape Infectious Diseases. “Most postlicensure safety reports have involved expected nonserious events, such as injection site pain,” he added.

Regarding reports of Guillain-Barré syndrome, Dr. Iskander said that there is no evidence that the vaccine causes this adverse effect. “Among the small number of confirmed cases, most vaccinees also received meningococcal conjugate vaccine, which might rarely be associated with Guillain-Barré syndrome,” he said. “There is also a baseline occurrence of [this disorder] among adolescents of about 1 to 2 per 100,000 persons per year.”

He also pointed out that syncope often occurs with vaccinations. “Among young adults up to age 25, nearly half have experienced a syncopal episode, so there appears to be a high baseline risk for syncope among the target age groups for this vaccine,” he said.

Dr. Iskander pointed out that both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics Red Book Committee suggest a 15-minute waiting period after vaccination to prevent injuries that might occur from postvaccination syncope. “Clinicians should also report clinically significant adverse events that occur after immunization to VAERS at http://www.vaers.hhs.gov.”

Margaret Stanley, MD, PhD, OBE, from University of Cambridge in Cambridge, United Kingdom, whose laboratory studies HPV, noted that the 2 HPV vaccines are very efficacious, achieving greater than 95% efficacy against precancerous HPV 16/18–related cervical disease. “No vaccine-related serious adverse events have been observed in the large phase 3 trials, and there is no evidence to date to suggest that there is a difference in the safety profiles of the 2 vaccines,” she said.

Note:
The study was funded by the US government. The authors have disclosed no relevant financial relationships. Dr. Stanley is a paid consultant for Merck Research Laboratories, GlaxoSmithKline Biologicals, and Sanofi Pasteur MSD.

Source:
International Conference on Emerging Infectious Diseases 2008: Board 150. Presented March 18, 2008.