By Gail Johnson, November 1, 2012
A human papillomavirus (HPV) vaccine may trigger fatal autoimmune or neurological events in some cases, two UBC researchers say. Their findings come as public-health authorities, who maintain that the shots are safe, are urging young women to get vaccinated to prevent cervical cancer.

Neuroscientist Chris Shaw and Lucija Tomljenovic, who has a PhD in biochemistry and is a senior postdoctoral fellow in UBC’s faculty of medicine, say that research on the HPV vaccine Gardasil (which is given in three shots over a six-month period) raises serious concerns and that the risk of adverse reactions is largely downplayed. In an interview at their lab, they maintain that the vaccine needs more scrutiny before health agencies promote it in public campaigns.

“For reasons that are not understood, some people are having terrible reactions to this vaccine,” Shaw says. “Some people are more susceptible. Most people who get these vaccines are fine.…But some people may get sick from these vaccines, so claiming that there are no adverse reactions aside from a sore arm is not strictly true.”

Shaw and Tomljenovic work out of UBC’s department of ophthalmology and visual sciences’ neural-dynamics research group. The two published a study called “Death after quadrivalent human papillomavirus

 (qHPV) vaccination: Causal or coincidental?” last month in Pharmaceutical Regulatory Affairs. The study focuses on two young women who were vaccinated with Gardasil and died following symptoms resembling those of cerebral vasculitis (inflammation of blood vessels in the central nervous system). Autopsies revealed no anatomical, microbiological, or toxicological findings that might explain the deaths. Shaw and Tomljenovic’s study showed that autoimmune vasculitis could have been triggered by certain HPV antibodies binding to the wall of blood vessels in the brain.

“The fact that many of the symptoms reported to vaccine safety surveillance databases following HPV vaccination are indicative of cerebral vasculitis but are unrecognized as such (i.e., intense persistent migraines, syncope, seizures, tremors and tingling, myalgia, locomotor abnormalities, psychotic symptoms and cognitive deficits), is a serious concern,” they wrote. “It thus appears that in some cases vaccination may be the triggering factor of fatal autoimmune/neurological events. Physicians should be aware of this association.”

Shaw and Tomljenovic concede that the study has limitations: only two case studies and no control group. Their research is ongoing.

They say the most frequently referenced study of the vaccine’s safety comes from pharmaceutical giant Merck & Co., which developed Gardasil, one of two vaccines approved for use in Canada. (The other is GlaxoSmithKline’s Cervarix.)

The Merck study involved almost 190,000 females who received at least one vaccine dose between 2006 and 2008. Published in the October 1, 2012, online edition of the Archives of Pediatrics & Adolescent Medicine, the study stated it “did not detect evidence of new safety concerns among females 9 to 26 years of age secondary to vaccination with HPV4 [Gardasil]”. “These findings support the general safety of routine vaccination with HPV4 to prevent cancer,” the study noted.

Shaw and Tomljenovic note that this study has limitations. “First, we could only detect new-onset conditions requiring ED [emergency department] visits or hospitalizations within 60 days after vaccination; it was not designed to investigate long-term safety outcomes or risk of HPV4–associated recurrence/progression of disease,” the Merck study said. “Second, despite its large size, this study may have had insufficient power to detect very rare conditions.”

The study was funded by Merck; the lead author receives research support from Merck, GlaxoSmithKline, and other drug companies. “The study sponsor, Merck & Co, provided substantial input into the study design and analytic plan,” Merck reported. “In collaboration with the Kaiser Study Team, the sponsor reviewed data analyses and helped draft and revise the manuscript.”

Dr. Monika Naus, the B.C. Centre for Disease Control’s medical director of immunization programs and vaccine-preventable-diseases service, says that HPV vaccines are safe. HPV infections cause almost all cases of cervical cancer, she notes, and it’s estimated the vaccine can prevent up to 70 percent of cases as well as precancerous changes to the cervix that require aggressive treatment. During last month’s Cervical Cancer Awareness Week, the organization encouraged women who were born between 1991 and 1993 to get vaccinated at no cost. B.C. began offering the vaccine for free to girls in grades 6 and 9 in 2008.

“Pap smears are still important for prevention of cervical cancer, but being vaccinated against 70 percent of the cause of precancerous lesions and cancer is a huge boon,” Naus says in a phone interview. “The clinical trials were large; they were done on thousands of women.

“Bad things happen to people regardless of whether they’re vaccinated,” she adds. “You can drop dead from any variety of causes.…In some of [the vaccine] postmarketing outcome data, the types of issues that have been identified have been attributed to oral-contraceptive use, which is common in this age group of women. That’s an important reason for why we need to have controls. You need to be able to attribute cause appropriately. Safety data is available from many countries’ use [of the vaccine], and there’s nothing concerning emerging.”

Naus adds that anyone who is concerned about the safety of the vaccine should speak to their primary health-care provider and gather information from reliable websites, not those that are “antivaccine”. “These are very effective, very safe vaccines,” she says.

Shaw and Tomljenovic, meanwhile, want the potential for adverse reactions to be acknowledged. “We don’t give medical advice; we’re not medical doctors,” Shaw says. “But if people recommend this vaccine, at least recognize there may be significant adverse reactions. Then people can make an informed choice.…Informed consent is something UBC believes in and the Canadian Medical Association believes in.”

The two are aware of the controversy that surrounds vaccines in general and emphasize that they are not antivaccine. But they can’t help but wonder whether their findings will be brushed aside simply because the topic is so heated.

“Science evolves by constantly probing and questioning,” Shaw says. “We don’t make policy, but we think…there are certainly more questions to be asked and more experiments to be done. The issue is not a slam-dunk; it’s not over.…In science, the debate is never over.”