Two articles and an editorial in the current issue of the Journal of the American Medical Association (JAMA) about the side effects and marketing of the cervical cancer vaccine are probably going to raise questions. They may also fuel the fires of concerns among some groups that have raised thorny political questions about the vaccine, especially as to whether or not this vaccine should be mandatory for young girls.
The primary “scientific” report in JAMA describes the results of a post-marketing surveillance program that monitors the side effects of new vaccines.
The study, written by researchers from the Centers for Disease Control and Prevention and the Food and Drug Administration is fairly straightforward.
In order to monitor reports of subsequent adverse reactions, the CDC and the FDA sponsor an adverse event reporting system called the US Vaccine Adverse Event Reporting System (VAERS). Anyone can submit a report of a suspected vaccine-related adverse event to this system, even if they are not the patient, a family member, a physician or other health care professional. Once the vaccine has been in widespread use for a sufficient period of time, those reports can be evaluated and researchers can determine whether or not there are any unsuspected safety signals, or if certain adverse events occur more frequently than would have been anticipated based on the initial clinical trials.
More than 23 million doses of the cervical cancer vaccine had been distributed in the United States between the date it was approved in June 2006 and December 31, 2008.
During that period of time, the VAERS had received 12,424 reports of adverse events following vaccination with the HPV vaccine. Most of the reports came from the manufacturer, but unfortunately those reports did not have patient information so they could not be verified. Also, many of the reports included multiple adverse reactions in single patients.
The most common reactions were syncope (fainting) in 15% of the reports, followed by dizziness, nausea, headache and reactions at the injection site.
772 of the reports--or 6.2%--were considered “serious.” These reports included 32 deaths. There were eight reports of serious allergic reactions, nine episodes of blood clots (deep vein thrombophlebitis or DVT) 31 episodes of ascending paralysis (Guillain-Barre Syndrome, or GBS) in addition to spinal cord inflammation, pancreatitis, blood clots to the lungs, convulsions, allergic skin reactions, and autoimmune disorders.
There were 1896 reports of fainting, and 15% of those reports included a fall. Of the people who fell, about 2/3 had a head injury as a result of the fall.
The researchers tried to verify many of the more serious events, but were stymied by the lack of medical information that was available. In addition, a number of the reports of serious events were based on hearsay, where the person who reported the event did not have first hand knowledge of the reaction.
Obviously, the greatest concern is with the reports of 32 deaths that may have been associated with the vaccine. Of those cases where data was available, there were several different causes of death including four that were unexplained.
The authors conclude that the safety profile was in line with what would have been expected from the initial clinical trials of the vaccine. They did point out, however, that there was a higher rate of syncope and blood clots (DVT) than was expected. They also noted that surveillance is continuing.
Syncope after vaccination is not a new problem with vaccinations. The authors note that fainting after a shot is not unusual in young people, especially young women between the ages of 11 and 18. They emphasized the need for patients, families, and health care professionals to follow recommended precautions after giving this vaccine, in order to prevent more serious injury.
The authors also noted that this reporting system is “passive.” That means it relies on people letting the CDC and the FDA know about adverse events. They also think publicity increased the number of adverse events that were reported since there were three times the number of reports for this vaccine compared to the rate seen for all other vaccines combined.
“The post licensure safety profile presented here is broadly consistent with safety data from pre-licensure trials. Because VAERS data must be interpreted cautiously and cannot generally be used to infer causal associations between vaccines and (adverse events), post licensure monitoring will continue and identified signals may be evaluated using epidemiologic observational studies.”
So that’s the science. Now for the more controversial part of this report, which calls into question how this vaccine was marketed and what role medical associations may have played into misleading their physician members about the vaccine.
The authors of this article, from the Columbia College of Physicians and Surgeons in New York, refer to “critical and unresolved questions” about the vaccine in terms of how it was marketed, whether the vaccine was being targeted to those young women who need it most, and whether the medical societies were really unbiased in their presentations about the vaccine.
The authors maintain that by marketing this vaccine to prevent cervical cancer as opposed to preventing infection with a virus resulted in the vaccine gaining greater acceptance in the community and among physicians. The authors claim that the public was led to believe that every young girl was at equal risk of getting cervical cancer, as opposed to focusing on young girls at greater risk of getting cervical cancer. Those girls at risk are frequently economically and educationally disadvantaged which results in a lower likelihood that they will follow cervical cancer screening recommendations as they grow into adulthood.
To me, the most disconcerting allegations in this article are leveled at “professional medical associations” (PMAs) which are physician membership organizations that are highly regarded and have a significant nationwide presence. The authors suggest that some of these organizations altered their professional focus and messaging surrounding cervical cancer as a result of corporate funding. They established well-resourced speaker bureaus funded by the manufacturer to provide continuing medical education lectures, including carefully designed scripts and slides. Even potentially controversial or difficult questions had very specific responses crafted as part of these kits.
The authors conclude:
“As marketing of this HPV vaccine demonstrates, pharmaceutical company campaigns can undercut the most cost-effective and appropriate use of new agents to the detriment of adolescent health. By making this vaccine’s target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to all adolescents maximized, and the subpopulations most at risk practically ignored…Under no circumstances should PMAs administer product-specific speakers’ bureaus, nor should they accept funding that requires them to report activity to the donor.”
These are serious comments. And don’t forget that they appear in JAMA, which is the medical journal published by the American Medical Association, the granddaddy of professional medical associations (although there is no suggestion that the AMA was engaged in any of these activities).
The editorial also discusses the complexity of decision making when it comes to evaluating the risks and benefits of a new medical treatment, such as the cervical cancer vaccine. The writer points out persistent lack of knowledge about the vaccine, such as the impact on cervical cancer rates 20 or 40 years from now, and the fact that more long term studies about the vaccine were needed but have not yet been reported.
The opinion of the editorialist is bound to be the topic of discussion in the medical community:
“The net benefit of the HPV vaccine to a woman is uncertain. 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.
“When weighing evidence about risks and benefits, it is also appropriate to ask who takes the risk, and who gets the benefit. Patients and the public logically expect that only medical and scientific evidence is put on the balance. If other matters weigh in, such as profit for a company or financial or professional gains for physicians or groups of physicians, the balance is easily skewed. The balance will also tilt if the adverse events are not calculated correctly.”
So what does the American Cancer Society recommend?
Our guidelines call for routine vaccination of girls ages 11 and 12, and as young as 9. We also recommend the vaccine for women ages 13 through 18 to “catch up” missed vaccines or to complete the series of three shots. We do not believe there is sufficient evidence to recommend for or against routinely vaccinating women between the ages of 19 and 26, and those women should have an informed discussion with their health care professional about the benefits and risks of the vaccine.
All of this discussion led me to go back to our original guidelines publication. We make every effort to have the best experts participate in our guidelines panels. We do not take funding from industry to support our guidelines efforts, and we do not gain financially from producing our guidelines. I do know that our panel spent countless hours reviewing the evidence, and discussing and debating many aspects of the HPV vaccine before they made their recommendations.
That said, I would be remiss if I didn’t note that a number of the experts on the panel do in fact have industry relationships related to the cervical cancer vaccine. These are, after all, the experts that everyone seeks for their opinions. I know many of them personally and by reputation, and all are highly regarded. But as I noted in last week’s blog on whether or not physicians routinely recommend the vaccine, there are situations where I feel obligated to note potential conflicts, and this is one of those situations.
Ultimately, you will have to make your own decisions and conclusions about what all of this means—especially if you have a daughter who is eligible to receive the vaccine. Far be it from me to tell you what to do, but I do continue to support our guideline recommendation.
There is nothing in these articles that would make me change my mind. Controversy is one thing, but good medicine is another. And many experts I know and trust believe this vaccine continues to be “good medicine.”