Gardasil's safety record normal: study

The safety record of Gardasil, a vaccine aimed at protecting girls and young women from cervical cancer, seems to be similar to that of other vaccines, a study of side-effect reports in the U.S. suggests.

The safety record of Gardasil, a vaccine aimed at protecting girls and young women from cervical cancer, seems to be similar to that of other vaccines, a study of side-effect reports in the U.S. suggests.

The vaccine protects against infections with some strains of the human papillomavirus, or HPV, that are said to be responsible for about 70 per cent of cervical cancers and most genital warts.

The vaccine does not appear to be causing any unusual side-effects, with fewer than one per cent of patients saying they experienced fainting, nausea or dizziness, Dr. Barbara Slade of the U.S. Centers for Disease Control and Prevention and colleagues reported in Wednesday's issue of JAMA.

"For 23 million doses that have been sent out, we've received 12, 424 reports of adverse events," Dr. Barbara Slade of the U.S. Centers for Disease Control and Prevention said in a journal release.

The rates were comparable to those of other vaccines given to girls the same age at 54 reports per 100,000 doses given, the researchers said.

The team found 772 of the adverse events, or 6.2 per cent, were serious, including 32 deaths, as well as reports of anaphylaxis (severe allergic reaction), dangerous blood clots and nerve injury that can cause paralysis.

(Researchers were able to verify 20 of the 32 deaths, with four reports from the manufacturer providing no further information and eight secondhand reports that could not be verified.)

"Most of the [adverse event] rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events," the study's authors concluded. Syncope is fainting, while VTEs are a form of embolism, or arterial obstruction.

The safety profile after the vaccine went on the market is "broadly consistent" with safety data from prelicensing trials, they added.

Adverse event reports do not show a vaccine or some other factor caused problems or deaths, only that they occurred after receiving a vaccine. Reactions can occur to the active ingredients in vaccines and the preservatives.

Specifically, for every 100,000 vaccine doses given, there were:

  • 8.2 reports of syncope or fainting.
  • 7.5 reports of local site reactions such as swelling at the injection site
  • 6.8 reports for dizziness
  • 5.0 reports for nausea
  • 4.1 reports for headache.
  • 3.1 for hypersensitivity reactions.
  • 2.6 for urticaria or skin rash.
  • 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barré syndrome, which can cause temporary paralysis.
  • 0.1  anaphylaxis and death.
  • 0.04 for transverse myelitis and pancreatitis.
  • 0.009 for motor neuron disease.

Gardasil's manufacturer, Merck and Co., said it was pleased the study reinforced the safety profile of the vaccine.

"We welcome continued study and discussion about the safety of this important vaccine," Dr.  Richard Haupt, pediatrician and head of the clinical program for Gardasil, said in a statement.

Health Canada's adverse drug reaction database includes one adverse reaction involving someone who received Gardasil, among other products, at the time of the reaction. Gardasil was not suspected as the cause of her reaction, and she fully recovered.

Net benefit?

An editorial accompanying the study questioned whether the risk is acceptable for inoculating a healthy population against a disease that can be detected through Pap screens.

The theory behind the vaccine is sound, in that if HPV infection can be prevented then cancer will not occur. But in practice, the issue is more complex, Dr. Charlotte Haug, of The Journal of the Norwegian Medical Association, said in a journal commentary.

The virus does not appear to be very harmful because almost all HPV infections are cleared by the immune system, Haug said. In a few women, infection persists and some women will develop precancerous lesions and eventually cervical cancer later in life.

"The net benefit of the HPV vaccine to a woman is uncertain," Haug wrote.

Personal decision

"Even if persistently infected with HPV, a woman most likely will not develop cancer if she is regularly screened. So rationally she should be willing to accept only a small risk of harmful effects from the vaccine."

A second article appearing  in the same issue questioned the marketing of the vaccine, and urged medical groups to be open about ties with pharmaceutical industry. Sheila Rothman and David Rothman of Columbia College of Physicians and Surgeons said Merck provided educational grants to professional medical associations to promote the vaccine.

"When they look through it, there wasn't any big alarm bells, but the story will need to be followed, " said Mark Evans, a family physician in Toronto, noting his family would go ahead and vaccinate their 12-year-old daughter, but that it's a personal decision.

"I wouldn't encourage that you get it, I would encourage you to go in and talk to your doctor or nurse about it."

Fainting is common after vaccines, which is why people are asked to stay at the office for 15 minutes after injections are given, Evans said.

About half of the cases of blood clots were in women with predisposing conditions, and use of the birth control pill can also be a risk factor for clots, he added. 

Gardasil is approved by Health Canada for females between the ages of nine and 26. The federal government announced in its March 2007 budget that $300 million over three years will be available to the provinces and territories in support of a national vaccination program. Many school boards have programs to administer the three shots over six months.

Last month, a study in the British Medical Journal also questioned the value of Pap screening for women under 25 because it had no detectable impact on rates of invasive cervical cancer up to age 30. Health Canada's website notes that most women who develop cervical cancer have not been screened in the three years prior to their diagnosis. A more sensitive test that detects DNA from HPV is also being developed.

With files from The Associated Press