'It's really wonderful we're making all the progress, but there are still many questions that need to be answered,' said Michele Manos, an infectious disease epidemiologist. 'One of those questions involves when to vaccinate girls -- and that won't be answered until the duration of the vaccine is fully understood.'

Researchers say the results confirm the success and safety of the vaccine Cervarix, which is designed to guard against two cancer-causing human papillomaviruses, HPV 16 and 18.

This is the most significant advance in cancer prevention in the last 50 years, said lead author Diane Harper, director of Gynaecologic Cancer Prevention Research at Dartmouth Medical School. We now have a vaccine that's 100 percent effective, she added.

She also emphasized the vaccine does not prevent cancer -- it prevents the virus that causes cervical cancer, the second most common malignant disease in women worldwide.

The research, conducted by Harper and several investigators, appears online Thursday in the British journal The Lancet.

Same Family of Viruses as Skin Warts

Around 800 women from the original clinical trial were included in the follow-up, conducted between 2003 and 2004. The women, who come from 32 sites around the world, represent a racially and ethnically diverse group, possibly the only global study with a planned longterm follow-up, Harper said.

Not only did the vaccine still appear strong after four years, the women encountered no vaccine-related diseases, Harper said. In other studies of HPV vaccines, the duration of effect, as it's called, was only three years. In general, vaccine duration varies greatly: some are needed only once-in-a-lifetime, and others last 10 years, as with tetanus. Researchers do not yet know the booster requirements for cervical cancer vaccines, or if boosters are even required.

Two cervical cancer vaccines are currently being developed: GlaxoSmithKline's Cervarix, which targets only HPV 16 and 18, and Merck's Gardasil, which prevents HPV 16, 18, 6 and 11; the latter two viruses cause genital warts. Cervarix could be released on the market as early as spring 2007, months after Gardasil's expected debut in fall 2006, Harper said.

HPV 16 and 18, in the same family of viruses as skin warts, are contracted through sexual activity, although genital contact alone can also spread the virus. These viruses are also very common: 80 percent of people will have an HPV genital infection in their lifetime. To develop cervical cancer, the virus must stay in the cervix long enough to change its cell structure.

Harper and colleagues also found the vaccine also offered a cross-protection, which means it also kept other HPV types at bay -- in essence, killing two birds with one stone.

Hoping for Worldwide Health Benefits

"It's really wonderful we're making all the progress, but there are still many questions that need to be answered," said Michele Manos, an infectious disease epidemiologist at Kaiser Permanente's Division of Research. "One of those questions," Manos said, "involves when to vaccinate girls -- and that won't be answered until the duration of the vaccine is fully understood."

Most girls' peak period for contracting HPV viruses is late teens to early 20s. Both Harper and Manos stressed the vaccine should not be given too early, which would miss that crucial time.

Manos also pointed out Americans' attitudes toward a potential cervical cancer vaccine are still unknown, and should be taken into account. The public's opinion and compliance are important issues of any new vaccination program, said Manos, who has studied HPV for 20 years.

In the United States, 14,000 women annually are diagnosed with cervical cancer, and around 4,000 will die, according to the National Cervical Cancer Coalition. But developing countries have carried most of cervical cancer's burden, accounting for about 85 percent of total annual cases. Many of these women don't have access to pap smears, a medical procedure which can detect cervical cancer early.

"It's a huge breakthrough. We're hoping to see the worldwide health benefits of this -- something like what happened with smallpox," Harper said. "We hope this is a cancer we can make go away."