Lubricant reduces virus risk
Mouse study points to preventive treatments for cervical cancer.
Commonly used spermicides and vaginal lubricants have a marked effect on the chance of infection with human papillomavirus (HPV), the virus blamed for a large majority of cases of cervical cancer.
The findings come from studies done in mice with the early stages of HPV infection by John Schiller and colleagues at the National Cancer Institute, Bethesda, Maryland.
The spermicide nonoxynol-9 increases the chance of infection, they found, whereas carrageenan, a vaginal lubricant, hinders the virus. Schiller and his colleagues are planning a clinical trial to test the lubricant's ability to prevent HPV infection in women.
HPV can persist only in humans, causing problems for making a mouse model of the infection. But the first stages of infection, when the virus enters the cell, is not species specific. Another problem is that HPV does not replicate well in cell cultures.
To get around both problems, Schiller's team created an HPV 'pseudovirus'. This has the same protein coat as HPV but a different genome, and it does replicate in cell cultures. It also carries a fluorescent tag, allowing researchers to track the progress of infection.
The pseudovirus mimics the initial phases of infection well, says Schiller. "No model is perfect," he says, "but we feel that ours is by far the best."
Treatment with nonoxynol-9 increased a female mouse's probability of being infected by HPV, the researchers write in Nature Medicine1. The spermicide has also been suspected of increasing the risk of HIV infection in humans.
Nonoxynol-9 is thought to aggravate the cells in the lining of the vaginal tract. Schiller thinks that this damage allows the virus to reach the underlying membrane and cause infection.
The study "demonstrates that some kind of damage to the top layer of the genital tract is absolutely key in infection," says Lesley Walker, of Cancer Research UK in Hull. "It could be key in understanding the early events in the development of cervical cancer."
Conversely, carrageenan stopped infection. Schiller's team had previously reported that HPV binds tightly to the lubricant. Schiller thinks he knows why this happens, but won't reveal his ideas yet.
The work highlights that intact cells in the lining of the genital tract are resistant to HPV infection, and won't even bind to the invading virus, says Schiller. The crucial step for infection seems to be the virus binding to the basement membrane that underlies these cells, he adds.
- Roberts, A. et al. Nature Med. Advance online publication doi: 10.1038/nm1598 (2007).