The largest review of the available evidence on the quadrivalent, or four-strain, HPV vaccine Gardasil, has found no evidence of any serious short-term or long-term safety issues. Bringing together the findings from clinical trials, post-licensure studies and data presented at scientific meetings but not yet published, the researchers focused particularly on autoimmune diseases, nervous system disorders, anaphylaxis, blood clots and stroke – but none of them is caused by the vaccine, they found.
“The big take home message for parents is that this is a reassuring study that supports what we already knew, that the HPV vaccine is a very safe vaccine,” said Michelle Berlin, M.D., the co-director of the Oregon Health and Science University Center for Women’s Health. “The most common side effects that we see are soreness at the injection site and that some children faint when they get the shot, but they do that with any other shot in adolescence too.”
Human papillomavirus, or HPV, is a common viral infection most often spread through sexual contact, though it can be spread by other intimate skin-to-skin contact methods or to a newborn during birth. Approximately 80 percent of sexually active individuals will eventually contract at least one of the 100 strains of HPV, and the vast number of infections go away on their own. Those that don’t, however, can develop into precancerous cervical lesions and, if not caught with a Pap smear, eventually cancer. Adequate screenings for other types of cancers linked to HPV, such as penile, anal and oral cancers, are not available.
Two of the strains that Gardasil protects against, HPV 16 and HPV 18, are responsible for approximately 70 percent of all cervical, vaginal, vulvar and anal cancers. The other two strains the vaccine prevents, HPV 6 and HPV 11, cause genital warts. A more recent formulation, Gardasil 9, includes five additional strains and, by preventing infection with those strains of HPV, expands prevention to 90 percent of HPV-related cancers.
“This is an incredibly well studied vaccine, with huge data sets and huge populations, and nothing has panned out as being significant as far as major adverse events,” said Dr. Stanley Block, a pediatrician in private practice in Bardstown, Kentucky, and a coauthor of the study recently published in the Pediatric Infectious Disease Journal. “We know the reality is that it protects against a tremendous number of deaths, cancers and chemotherapies for your daughters and your sons somewhat too.
Among the studies Block and his colleagues reviewed were the five clinical trials, involving 29,364 male and female participants, used to seek approval for the vaccine from the FDA, licensed in 2006 for girls and women and then in 2009 for boys and men. They also looked at studies evaluating the vaccine in pregnant women, those with HIV and those with lupus.
“In the 8 years of post-licensure vaccine safety monitoring and evaluation conducted following the initial licensure of HPV4 in the U.S., no serious safety concerns have been identified in any study conducted worldwide,” the researchers found. By the time the long-term arm of the clinical trials concludes, researchers will have 14 years of follow-up data.
One of the most important ways researchers investigate possible severe side effects of a vaccine is to use the Vaccine Safety Datalink. Usually, the researchers first look at what has been reported to the Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system to which anyone can make a report about something happening after getting a vaccine (whether it’s related or not). There is no evidence that the incidents reported to VAERS are caused by the vaccine, but when reports show up in VAERS, especially multiple times, researchers can use the Vaccine Safety Datalink to investigate whether those conditions might be related to the vaccine. The VSD includes more than 9 million participants from seven healthcare systems across the U.S.
The researchers compared how many cases of Guillain-Barre syndrome, blood clots, stroke, appendicitis, allergic reactions, seizures and fainting occurred to those who received the vaccine to the number of these cases in those who never received the vaccine. The VSD studies for the HPV vaccine included than 600,000 doses of the vaccine. The only condition that appeared more often among those receiving the vaccine was blood clots, but close examination of those cases showed that all the girls with blood clots had other risk factors that increased their likelihood of a blood clot – using birth control pills, smoking, obesity, a long-term hospitalization or an underlying blood clotting disorder.
The researchers also reviewed the three studies of HPV safety conducted in Denmark and Sweden. One of these, involving nearly 1 million girls, looked for 53 different conditions, including blood clots and autoimmune and neurological disorders, and found no link between the vaccine and serious conditions. Another Danish study of more than 1.6 million girls and women similarly found no risk for blood clots, and the third, involving nearly 4 million females, found no link between the HPV vaccine and multiple sclerosis or any similar disease.
Finally, several large studies involving the patient population of Kaiser Permanente Southern California looked for possible links between the HPV vaccine and 50 different conditions, including multiple nervous system and autoimmune disorders. Again, no dice.
Despite these reassuring findings, however, some parents still express hesitancy about the vaccine, owing largely to misinformation and irresponsible media coverage. Part of the fault lay with how the vaccine has been presented to parents and families, suggested Berlin. “It was not promoted as a cancer prevention vaccine,” she said. “That’s how it should have been framed.”
She points out that all the data so far supports the vaccine as being “very, very safe,” and researchers are continuing to follow the initial populations who received the vaccine, just as has happened with all past vaccines. The path Gardasil took to FDA approval did not differ from the path every other vaccine has taken for the past half century at least.
The effects of cervical cancer are huge,” Berlin said. “No woman in the United States should die of cervical cancer in this day and age. If we can get everyone who needs to be, vaccinated, we can dramatically reduce the number of women who die of this preventable cancer.”