Chicago Tribune - July 14, 2006
Peter Gorner, Tribune science reporter, pgorner@tribune.com

In a test tube, carrageenan inhibits the infectious ability of genital HPV with nearly a thousand-fold greater potency than other inhibitors tested, according to National Cancer Institute researchers, who reported their findings in Pathogens, a peer-reviewed journal published by the Public Library of Science.

Effectiveness unproven

How effective the compound would be in the human body remains to be demonstrated, but the discovery raises the possibility that carrageenan could be used with vaccines, condoms and lubricants as a protection against HPV. The chemical is extracted from marine red algae, or seaweed.

About 10,000 American women are diagnosed with cervical cancer each year; about 250,000 women worldwide die from the disease annually.

The human papilloma virus normally attacks cells by attaching to the proteins on the cell surface and then using chemicals to work its way in. Carrageenan blocks this process by attaching to the virus and preventing its access to cells.

The carrageenan discovery was made in the lab of Dr. John Schiller, senior investigator at the National Cancer Institute, who also was a key player in the initial development of the HPV vaccine.

Schiller was quick to put the new finding in perspective.

"Our results do not prove that carrageenan will work as a practical HPV topical microbicide," he said in a prepared statement.

"The potent inhibition of infection of cells in dishes, coupled with the fact that carrageenan-based products are already in use, are promising. But we will need to do a well-controlled clinical trial before use of any of these products as an HPV inhibitor could be recommended."

Still, Schiller said he and his colleagues were "floored" by how much better the compound is than anything else they have tested.

"An effective HPV microbicide could reduce the burden of HPV-related genital disease in women," Schiller said.

Christopher Buck, lead author of the study and a postdoctoral fellow at the National Cancer Institute, methodically tracked down and tested potential inhibitory compounds that were being considered as topical treatments for other infectious agents.

Because carrageenan was already in clinical trials in South Africa as a topical HIV inhibitor, Buck tested it against the HPV virus. It turned out that HPV is much more sensitive to carrageenan than HIV is.

"When carrageenan came up to be the clear winner, Chris started to search for products that might contain it," Schiller said.

"Although, carrageenan was identified in a systematic screen, the serendipity that this seaweed-derived compound is already used in over-the-counter products for genital application is really quite amazing."

The vaccine is virtually completely effective against some HPV strains, particularly two that are the most aggressive and most highly associated with cervical cancer. The vaccine also works on strains associated with genital warts.

But there are still multiple strains of HPV that won't be covered by the vaccination.

This kind of cancer requires multiple weapons, said Dr. Connie Trimble, an HPV researcher at Johns Hopkins University. Trimble was involved in the early preventive vaccine trials and is currently working on a maintenance vaccine for women who already have HPV.

She called the latest discovery "a great thing."

"With all the potential tools now, we could really start to think about the end of cervical cancer. Between the vaccines and some of the prophylactics--wouldn't that be a medical success story!"

The new vaccine doesn't prevent infection against every strain--more than 100 have been discovered so far--and its cost--about $360 for the three necessary doses--make it the world's most expensive vaccine.

That could be prohibitive, especially for women in developing countries.

Another member of the research team whose work led to the vaccine, Dr. Doug Lowy, chief of the Laboratory of Cellular Oncology at the National Cancer Institute, said he believed the limits of the vaccine should not be minimized.

"It's said to cover 70 percent of the viruses blamed for cervical cancer, which means that you could be infected by one or more of the remaining 30 percent and not be protected," Lowy said.

"So, I can imagine carrageenan could serve as an adjunct. We wouldn't expect it to be as efficacious as the vaccine--you have to use it all the time to prevent infection. But the vaccine's just too expensive for some parts of the world."

Carrageenan's safety profile for long-term vaginal use may make it useful as an inexpensive topical microbicide for blocking the sexual transmission of HPV.

Recognized as safe

"If people wanted to, they could run a clinical trial tomorrow because carrageenan falls under the FDA category of GRAS--Substance Generally Recognized as Safe," Lowy said.

"We checked over-the-counter products and found several that already are inhibitory. But the efficacy hasn't been shown to be effective in a controlled clinical trial.

"It's entirely possible that it could be tried and found not very effective. We hope that's not the case. We think the tissue culture data are strongly suggestive that it would be well worthwhile to carry out the clinical trial that addresses that question."

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