Immunization Issues

Before being licensed, the human papillomavirus (HPV) vaccine was tested in more than 21,000 girls and women 9 to 26 years of age in many countries around the world, including the United States. These studies found that the HPV vaccine was safe and effective. However, some vaccine recipients experienced pain, swelling and redness at the injection sites.

The World Health Organization’s Global Advisory Committee on Vaccine Safety recently reviewed the data—both published and unpublished—about the safety of HPV vaccine collected after the vaccine was licensed and administered to women around the world.1 They observed that both severe allergic reactions and fainting had been reported after HPV vaccination. They also noted that there was no convincing evidence to associate HPV vaccine and demyelinating diseases—a group of diseases such as multiple sclerosis or Guillain-Barré Syndrome, in which there is loss of the insulating envelope that surrounds nerves.

The Centers for Disease Control and Prevention (CDC) reported that since licensure in June 2006, through August 31, 2008, more than twenty million doses of HPV vaccine had been distributed in the United States and that 10,326 adverse events following immunization had been reported to the Vaccine Adverse Events Reporting System (VAERS).2 The most commonly reported adverse events were fainting and dizziness. Studies using the Vaccine Safety Datalink (VSD), however, did not show an increase of fainting after HPV vaccine but rather suggested that increased fainting occurred among females 13 years and older after receiving any vaccine.3 Thus, health providers who are administering vaccines to this age group should be aware of these symptoms and take appropriate measures to prevent injuries. The rapid occurrence of these symptoms suggests that these vaccine recipients should be asked to sit or lie down for 15 minutes after vaccination.4

In Australia, severe allergic reactions (anaphylaxis) were reported to occur at a rate of 2.6 per 100,000 doses of HPV vaccine.5 However, as of July 20, 2008, when approximately 375,000 had been vaccinated at the VSD sites in the United States, no increased rate was detected when immunized females were compared to unimmunized women3. Other outcomes that are being monitored by active surveillance employing the VSD include Guillain-Barré Syndrome, seizures, stroke, venous thromboembolism (birth control and pregnancy increases this type of risk), and other allergic reactions.

The manufacturer also maintains a registry to evaluate the outcomes of pregnancies when the mother was inadvertently immunized with HPV vaccine during pregnancy. Although the numbers are small (about 800), the rates of spontaneous abortion, fetal deaths and congenital anomalies after HPV vaccination are similar to published rates when the vaccine has not been administered.6

Reliable information about the safety of HPV vaccine can be found at the CDC Web site >>

Misinformation about HPV Vaccine Safety

Misinformation (erroneous information) about vaccine safety causes parents to become confused and, as a consequence they may delay their children’s immunizations. This can have tragic consequences. The failure to vaccinate leaves individual children and communities vulnerable to serious and potentially life-threatening diseases.7

Recently, misinformation about the safety of HPV vaccine8 has been widely disseminated in the media. The misinformation was based upon erroneous interpretations of VAERS reports. The VAERS database cannot be used to compare adverse events reported after different vaccines. Nor can it be used to determine whether a reported adverse event was due to the vaccine or not—because it contains events that may have occurred by coincidence. Moreover, VAERS is susceptible to reporting biases, it does not consider unvaccinated people, and there is no denominator:

• Coincidence. Illnesses can be first recognized at about the same time that vaccines are given just by coincidence. In fact, one group of researchers analyzed what were the rates that some conditions occurred on any random day among preadolescent girls and young women who had not been given any vaccine. Of course, if a vaccine had been given this would have been the frequency that these conditions would have been seen by chance alone—in which case, these cases would likely have been reported to VAERS.9
• Without a comparison group, it is not possible to determine whether the adverse events are more frequent, less frequent, or are occurring at the same rate among the vaccinees.
• Reporting Biases. ‘Selection bias’ is a term that vaccine researchers use to describe a non-random selection of study subjects that could have influenced the results. The VAERS database includes events that are not reported for a variety of reasons as well as events that may be over-reported; for example, when the observer believes that the vaccine caused the outcome. Reports can be entered by anyone and are not always verified.
• Denominator. Without knowing the size of the population being studied it is not possible to compare rates of adverse events between those that have been vaccinated and those who were not, for example.

What VAERS does is to collect reports of untoward events that occur after vaccination. These data then permit the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration, and other researchers10 to look for possible uncommon side reactions to vaccines that might not have been identified during the pre-licensure trials. They use the VAERS database to generate hypotheses that can be tested using more sophisticated epidemiologic tools, such as case-control studies employing the VSD.

References

• 1. WHO. 2009. Global Advisory Committee on Vaccine Safety, 17-18 December 2008. Wkly Epidem Rec. 84(5): 37-40.
• 2. Calryar A. 2008. Presentation to the Advisory Committee on Immunization Practices, October 22, 2008. Accessed February 10, 2009.
• 3. a. b. Gee J, Naleway A, Shui I. 2008. Presentation to the Advisory Committee on Immunization Practices, October 22, 2008. Accessed February 10, 2009.
• 4. American Academy of Pediatrics. 2006. General instructions for vaccine administration. In: Pickering LK, Baker CJ, Long SS, et al. eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill: pages 18-19.
• 5. Brotherton JML, Gold MS, Kemp AS, et al. 2008. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ 179(6); 525-533.
• 6. Dana A. 2008. Vaccine Safety Update: Vaccine Pregnancy Registry. Presentation to the Advisory Committee on Immunization Practices, October 22, 2008. Accessed February 10, 2009.
• 7. Myers MG and Pineda D. 2008. Do Vaccines Cause That?! A Guide for Evaluating Vaccine Safety Concerns. I4PH Press. Galveston, Texas.
• 8. Fisher BL. 2009. Gardasil death & brain damage: a national tragedy. NVIC Vaccine E-Newsletter distributed by [email protected] on behalf of NVIC on Monday, February 9, 2009.
• 9. Siegrist CA, Lewis EM, Eskola J, et al. 2007. Human papilloma virus immunization in adolescent and young adults: A cohort study to illustrate what events might be mistaken for adverse reactions. Pediatric Infectious Diseases Journal 26: 979-84.
• 10. Borja NL, Benavides S, Christnsen C. 2009. Human papillomavirus vaccine safety in pediatric patients: An evaluation of the Vaccine Adverse Event Reporting System. Ann Pharmacother 43(2): 356-9.