, enhanced mTORC1 signaling, and altered brain cytoarchitecture,” the researchers wrote. “Our study is the first to provide an association between HPV16 infection and a neurological disorder and the first to detect HPV16 in human brain.”
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“The study is very intriguing,” said Delia Talos, MD, assistant professor of neurology at New York University, who does epilepsy research but was not involved with this study. “No one has ever suggested this before.”
She said that while “it is very tempting to say that this terrible disease could be prevented,” more work is needed to confirm the findings and understand the possible clinical implications.
Other researchers told Neurology Today they were impressed by the design of the study and the strength of the results. Leon Epstein, MD, the Derry A. and Donald L. Shoemaker professor of pediatric neurology at Northwestern University, said the paper was “very persuasive” and an example of the insight that can result when scientists think creatively across disciplines.
He said the researchers “asked a totally testable question: Was the HPV16 E6 oncoprotein present in FCDIIB tissue? The answer was yes, and specifically the protein was localized in balloon cells.”
“I think this is a very important study if the role of HPV in the pathogenesis of focal cortical dysplasia is confirmed by future studies,” said Dr. Epstein, whose research specialty is neurovirology. He said “it is possible that the HPV vaccines currently used to prevent cervical cancer might also result in fewer children born with focal cortical dysplasia and associated epilepsy.”
Dr. Crino and his team noted in their paper that “one pivotal unresolved issue is the mode of HPV16 transmission in FCDIIB.”
“Because it is believed that FCDIIB forms during embryonic brain development, a possibility is transplacental HPV16 infection of progenitor cells in the developing brain,” they wrote.
They noted that the transplacental transmission rate of HPV among women with either known HPV infection, an abnormal PAP smear, or genital warts is 12.2 percent. Overall, an estimated 26.8 percent of women aged 14 to 59 in the US have been infected with HPV, though many of them are unaware of it because they have no symptoms. The researchers speculated that even in the absence of symptoms in the pregnant woman, the HPV virus may pass through the placenta.
Erle Robertson, PhD, professor of microbiology at the University of Pennsylvania, who studies tumor virology, told Neurology Today that he doubted that HPV16 is the sole cause of FCDIIB but rather that it is one of a number of factors involved in the disease.
Still, he said, the study underscores how much there remains to be learned about viruses and their role in a wide variety of diseases.
“We are dealing with a huge number of organisms and we're just beginning to understand their connection to human disease and cancer,” Dr. Robertson said.
Dr. Crino said his team plans to study brain tissue from patients with other forms of cortical dysplasia to determine whether HPV16 and related virus strains are present. Another area of potential research, he said, if to see if the mTORC1 signaling pathway, which is activated in focal cortical dysplasia, could be targeted in treatment.
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