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Lubricant Blocks HPV Infection in Mice

Irish moss, a major source of carrageenanDepartment of Fisheries and Oceans Canada

Researchers have moved one step closer to developing a topical microbicide that can prevent infection by human papillomaviruses (HPVs), the most common sexually transmitted infection in the U.S.

There are more than 100 types of HPVs, over 30 of which are passed between people through sexual conduct. Most HPV infections don't cause noticeable symptoms and go away on their own, but some HPV types can cause cervical cancers or genital warts. Women can reduce their risk of HPV infection by using condoms, but the method isn't 100% effective. A recently approved vaccine prevents infections by 4 HPV types that together cause about 70% of cervical cancers and 90% of genital warts worldwide. Vaccines targeting other HPV types are also under development. However, a topical microbicide, a compound that could block HPV infection in the first place, would be a useful addition to the arsenal of anti-HPV weapons.

Dr. John Schiller and his colleagues at NIH's ×îÐÂÂ鶹ÊÓƵ Cancer Institute (NCI) had previously found, using cells growing in the laboratory, that an inexpensive gelling agent called carrageenan could block HPV from infecting its target cells. Carrageenan is extracted primarily from red algae and used in a wide variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Having identified a compound that could block HPV in the laboratory, the researchers set out to develop a mouse model to test whether it could block infection in the body.

The team developed an HPV "pseudovirus" composed of the two proteins that form the virus's coat and a "reporter" gene inside to replace the virus genome. Such pseudoviruses are thought to carry out the early phases of infection much like the virus itself does. As the researchers reported online on July 1, 2007, in Nature Medicine, the pseudovirus they created was able to infect the mouse genital tract.

Having established a model system, the researchers next tested to see whether compounds used in vaginal products affect susceptibility to infection. They found that a widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased the rate of infection. They then tested 2 commercial carrageenan-containing lubricants and found that they blocked infection. Carrageenan prevented HPV infection in the presence of N-9 as well.

These results raise the possibility that over-the-counter vaginal contraceptives containing N-9 may raise the risk for genital HPV infection in women. In contrast, carrageenan may serve as an effective topical HPV microbicide. The compound is currently being studied as a candidate topical microbicide against HIV. Carrageenan is considerably more active against HPV in the laboratory. Schiller and his colleagues are now planning a clinical trial to see if it can block HPV as effectively in the human body.

— by Harrison Wein, Ph.D.