3 “HPV vaccine … in our offices”—is confirmed safe and efficacious
Joura EA, Kjaer SK, Wheeler CM, et al. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine. 2008;26:6844–6851.
Centers for Disease Control and Prevention (CDC). Syncope after vaccination—United States, January 2005–July 2007. MMWR Morb Mortal Wkly Rep. 2008;57:457–460.
Centers for Disease Control and Prevention (CDC). Information from FDA and CDC on Gardasil and its safety. Available at: http://www.cdc.gov/vaccinesafety/vaers/FDA_and_CDC_ Statement.htm. Accessed February 12, 2009.
Kuehn BM. CDC panel recommends vaccine for smokers; reviews HPV safety data. JAMA. 2008;300:2713–2714.
The vaccine that protects against certain types of HPV, and probably against cervical cancer caused by those types, wasn’t approved by the FDA when the March 2006 “Update on Cervical Disease” was published. Preapproval expectations were high at the time; what we have witnessed since approval of Gardasil (Merck) has, in fact, exceeded earlier expectations.
As of August 31, 2008, more than 20 million doses of Gardasil have been administered. A CDC survey of 3,000 US adolescents 13 to 17 years old showed that one of every four received at least one shot of the vaccine in 2007, the first full year after approval. This uptake of the HPV vaccine during its first year is significantly better than 12% for the meningococcal vaccine and 11% for Tdap in the year after their introduction.
Is the vaccine efficacious?
Recent data from Joura and colleagues, based on more than 6 years of follow-up of women immunized with the quadrivalent vaccine, have not shown any decrease in protection from CIN 3+. There has been concern, however, that falling antibody levels that have been noted, particularly against HPV type 18, may indicate reduced protection from high-grade squamous or glandular disease.
To clarify the matter, these investigators evaluated efficacy data on the 40% of vaccine subjects who were anti-HPV 18-seronegative at the end of the study. Despite the inability to document antibodies to HPV 18 in these subjects, efficacy against HPV 18-related CIN 3 or adenocarcinoma in situ remained high at 98.4% compared with the placebo group. Th ese results suggest that vaccine-induced protection is high despite lower-than-detectable anti-HPV 18 titers.
How safe is it?
The safety of the HPV vaccine was studied in seven clinical trials in more than 21,000 girls and women 9 to 26 years old before it was licensed. The conclusion was that this is a very safe vaccine. But much has been made in the media—and even in a few peer-reviewed articles in the medical literature—that nevertheless questions the safety of Gardasil, and there is little doubt that clinicians who administer the vaccine have been bombarded with questions about this by their patients.
As of August 31, 2008, there were 10,326 Vaccine Adverse Event Reporting System (VAERS) reports of adverse events following Gardasil vaccination in the United States: 94% were considered nonserious and 6% were serious. These numbers appear great, but a 6% rate of serious adverse events is only about one half of the 10% to 15% rate observed after other vaccines made their debut.
VAERS, one of three systems utilized to monitor the safety of all vaccines after licensing and marketing in the United States, is open to the public. This means that it collects data without verifying the relationship of the adverse event to the vaccine other than proximity of timing. In a joint July 2008 Web-site posting, the CDC and FDA said: “In some media reports and on some web sites on the Internet, VAERS reports are presented as verified cases of vaccine deaths and injuries. Statements such as these misrepresent the nature of VAERS surveillance system.”
As part of ongoing surveillance, the CDC met in October 2008 to review Gardasil safety data. A synopsis of findings follows.
Reports of nonserious adverse events include syncope, pain and swelling at the site of injection (the arm), headache, nausea, and fever. The most common side effect reported to VAERS is syncope.
The FDA-CDC report emphasizes that syncope as a vasovagal reaction can occur after any vaccination, particularly in an adolescent. Syncope is not serious unless the patient is injured as she falls.
Major adverse events
Of course, greatest concern over the safety of the HPV vaccine is with reports of major adverse events following administration—including death. The October 2008 FDACDC review says that careful evaluation by medical experts of all serious reports has not found a common medical pattern to suggest that any were caused by the vaccine. Here is a summary of serious adverse-event reports submitted to VAERS between June 8, 2006, and August 31, 2008.