Study lead author Dr Chun Chao, a research scientist at the Kaiser Permanente Department of Research & Evaluation in Pasadena, California, said in a statement released on Friday, that:
"This kind of safety information may help parents with vaccination decisions."
""These findings offer some assurance that among a large and generalizable female population, no safety signal for autoimmune conditions was found following HPV4 vaccination in routine clinical use," said Chao.
Gardasil is a "quadrivalent" vaccine because it helps protect against 4 types of HPV. In girls and young women age 9 to 26, it targets 2 types that cause about 75% of cervical cancers, and 2 other types that cause 90% of cases of genital warts.
The vaccine, which is given as three injections over six months, also helps protect boys and men age 9 to 26 against 90% of cases of genital warts.
Genital warts is the most common sexually transmitted infection in the US, where it infects about 6.2 million people every year. It can also lead to cervical cancer in women.
Gardasil received US Food and Drug Administration (FDA) approval in 2006. But a longstanding concern about links with autoimmune disorders has surrounded the vaccine, and many parents won't let their children be vaccinated because of this.
However, Chao and fellow co-investigators from Kaiser Permanente told the press "most speculated associations have stemmed from case reports that have not been confirmed by large, controlled epidemiologic studies", and their investigation "presents findings from a well-designed, post-licensure safety study of the vaccine on a large, ethnically diverse population".
For the study, Chao and colleagues used electronic health records of 189,629 girls and women age 9 to 26 years in California. The participants had been followed for six months after receiving each dose of the quadrivalent HPV vaccine in 2006-2008.
They found no increase in any of 16 autoimmune disorders in the vaccinated population compared to a matched population of non-vaccinated girls and women. The 16 autoimmune disorders they looked for were:
"... immune thrombocytopenia, autoimmune hemolytic anemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, type 1 diabetes, Hashimoto's disease, Graves' disease, multiple sclerosis, acute disseminated encephalomyelitis, other demyelinating diseases of the central nervous system, vaccine-associated demyelination, Guillain-Barré syndrome, neuromyelitis optica, optic neuritis and uveitis."
The researchers explained that the clinical trial data on the vaccine, and the subsequent adverse event reports, have important limitations when it comes to assessing its safety profile.
This is because clinical trials are often based on a highly selected group of participants, the sample sizes are too small, and the follow up is too short, to catch rare safety events such as autoimmune disorders.
And the adverse event reports are not easy to interpret because there is no comparison group, and it is hard to tell if the condition developed before or after the vaccine.
So in their study, Chao and colleagues used methods like in-depth reviews of medical charts to ensure accuracy of diagnosis and that the disease occurred after vaccination. Plus, disease incidence in the vaccinated group was contrasted with incidence in a comparable unvaccinated group.
The results showed that:
- Overall, there were 1,014 new-onset cases of an autoimmune disorder, of which 719 were eligible for case review, and 31 (40%) were confirmed as new onset (ie emerged after vaccination).
- Of these cases, "no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition".
- None of the estimated incidence rate ratios was signficantly raised, except that for Hashimoto's disease (IRR = 1.29, 95% confidence interval: 1.08-1.56).
- "Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions."
The study appears to have been well received by experts not connected to the investigation.
Dr. Harry Fischer, chief of the division of rheumatology at Beth Israel Medical Center in New York City welcomed the findings and described the study as well-designed:
"This article speaks to the safety of the vaccine and helps to confirm that it does not contribute to the development of autoimmune diseases," he said, in a report from USA Today.
Merck & Co funded the study.