Vaccine may head off genital cancer in women

Therapeutic shots can wipe out precancerous growths caused by HPV

A series of shots can knock out genital lesions in women infected with a dangerous strain of human papillomavirus, or HPV, a new study finds. Although the experimental vaccine wasn’t effective in everyone tested, most of the women showed benefits and many appear to have developed long-lasting immunity against this strain of HPV and the precancerous growths it can spawn.

Two other vaccines, Gardasil and Cervarix, have been approved to prevent HPV infection in girls and young women who have not yet been exposed to the virus. The new vaccine is different; it can successfully treat active HPV infection that has triggered the development of the precancerous growths, researchers report in the Nov. 5 New England Journal of Medicine.

“This is a wonderful demonstration that these lesions can go away with vaccination,” says cancer immunologist Olivera Finnof the University of Pittsburgh School of Medicine. In the best-case scenario, these shots will deliver long-lasting protection, but only large-scale testing and extended follow-up will establish that, Finn says.

Researchers recruited 20 women who had such skin lesions affecting external genital tissue. The tissue abnormalities, caused by HPV-16, the most common cancer-causing strain of the virus, cause pain, itching and burning, says study coauthor Gemma Kenter, a gynecologist who worked on the study while at Leiden University in the Netherlands. Although the lesions can be removed with laser treatment or surgery, they commonly recur, says Kenter, now at VU University Amsterdam.

All the volunteers received the new vaccine in a series of three or four injections that contain synthetic versions of two HPV proteins, dubbed E6 and E7. The vaccine alerts the immune system to produce T cells — a type of white blood cell — that will target any cells making these proteins.

Two years after vaccination, these vulvar intraepithelial lesions had disappeared in nine women and showed partial improvement in four others. One additional participant appeared to benefit but died of heart failure before the trial was completed.

Six women failed to improve. While it remains unclear why six women derived no benefit, Kenter says, all had large lesions and most had been fighting the precancerous growths for 10 years or more.

The new vaccine mobilizes T cells, immune agents that can root out viruses that have already invaded a cell, says Finn. Viruses survive by incorporating their DNA into a cell’s genetic material. The resulting genetic changes induce HPV-infected cells to produce viral proteins, which contribute to a cell’s aberrant growth.

However, cells making E6 and E7 proteins get the attention of roving T cells. These immune sentinels respond by pouring out interferon-gamma, a cell-signaling molecule. It serves as a fire alarm, attracting immune troops to kill HPV-infected cells.

HPV is extremely common, often infecting women without causing symptoms. The new vaccine mimics the way most women clear HPV infections without ever developing lesions or cancer.

Among women who benefitted from the vaccine in the new study, the body cleared out infected cells, which Gardasil and Cervarix vaccines have not been shown to do, Kenter says. Those vaccines stimulate production of antibodies that lie in wait for newly arriving viruses — which makes them very effective in girls and young women who have never been exposed to HPV. It remains unclear how effective those vaccines will be for women in their 20s and older who may have a latent HPV infection, Kenter says.

For now, the goal will be to use the new vaccine therapeutically – if it gets approval — in women with precancerous genital lesions, Kenter says. The Dutch team is already working on a larger trial.

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