An experimental vaccine designed to protect against the virus that causes virtually all cases of cervical cancer was completely effective in a study being published today.
If the same results are found in a large, international study now underway, this finding could lead to the first human vaccine whose specific purpose is to prevent cancer.
The vaccine protects against a form of the human papilloma virus (HPV), which causes a painless infection of the cervix, the necklike entrance to the womb. It is extremely common, occurring in about half of American women sometime during their lives. While relatively few of those women go on to develop cervical cancer, nearly all cervical cancers that do occur are the result of long-standing HPV infection.
"This is pretty compelling evidence that this may be what people are looking for as a cancer-preventing vaccine," said Christopher P. Crum, a pathologist at Brigham and Women's Hospital in Boston and an expert on cervical cancer. "There are a lot of other issues to address, but the proof of principle has been made."
In a separate study, a different group of researchers reported that an experimental vaccine against genital herpes protected most women from getting that virus. (It did not protect men.)
Genital herpes infection is less common than HPV, affecting about one in four women and one in five men. It can have catastrophic effects in the rare instances that it is transmitted to a fetus during pregnancy or birth.
Together, the studies raise the possibility that the two vaccines might eventually become a routine part of the medical care of teenage girls, and could be administered before most become sexually active.
Although there are more than 30 types of HPV that can infect human beings, one of them -- type 16 -- is responsible for about half of all cervical cancers. The experimental vaccine, made by Merck Research Laboratories, protected only against that one, although future formulations are likely to also protect against the less common HPV types that can cause cervical cancer.
The new study looked at the experience of about 1,500 women between the ages of 16 and 23 who were randomly assigned to get either three shots of the vaccine or three placebo shots over six months.
In the year and a half after the last shot, 41 cases of HPV-16 infection were detected, nine accompanied by precancerous changes in the cervix. All HPV-16 infections were in women who got placebo shots; women who got the vaccine had none. Each group also included 22 women with precancerous changes not associated with HPV-16 infection (but presumably arising from infection with other HPV types).
"It was certainly a wonderful surprise when we got the preliminary analysis. This is very exciting news," said Kevin A. Ault, an obstetrician and gynecologist at the University of Iowa and one of the authors of the report appearing in today's New England Journal of Medicine.
The statistically perfect performance of the vaccine appears to arise from its unusually strong ability to stimulate protective antibodies. Women getting the vaccine had about a 60-fold higher concentration of antibodies in their bloodstreams than women who acquire HPV-16 and clear it on their own (as is the case in about 9 out of 10 infections). The vaccine consists of virus-sized particles that have the molecular shell of HPV-16 but nothing inside, making them harmless mimics of the real thing.
The trial has a year to go before its planned end. The researchers and the ethics advisory boards overseeing them have decided to let it continue to obtain more detailed data, said Kathrin U. Jansen, senior director of vaccine research at Merck Research Laboratories.
Once the study is finished, women in the placebo group will be offered a newer vaccine incorporating four HPV types, including HPV-16, she said. That "quadrivalent" product is designed to protect against virus types associated with about 85 percent of cervical cancers. It is now being tested in a tens of thousands of women in the United States, Latin America, Europe, Asia and Australia.
In neither study will researchers wait until cancer develops. That is because the precancerous condition (known as "dysplasia") can be easily cured by cutting out part of the cervix, an operation that in most cases does not affect a woman's ability to become pregnant or carry a child.
Cervical cancer is relatively rare in the United States, with about 13,000 new cases and 4,100 deaths each year. Mortality has been falling for 30 years, the result largely of widespread screening for the disease with Papanicolaou (Pap) tests, in which cells from the cervix are examined under a microscope.
Worldwide, cervical cancer was responsible for 258,000 deaths last year, according to the World Health Organization's World Health Report, published last month. In decreasing order, breast, lung, stomach and colon cancers caused more.
In places where Pap screening is not routine, however, cervical cancer exacts a heavy toll. In sub-Saharan Africa, for example, it's the leading cancer death in women, ahead of liver cancer. Infection with the AIDS virus increases a woman's risk of becoming chronically infected with HPV, and also leads to a more rapid decline in women with cervical cancer.
Although the disease burden from cervical cancer is low in the United States, the economic burden of looking for it is high. About $3 billion annually is spent on Pap smears, biopsies of women with abnormal findings, and other services associated with HPV infection. Much of this could presumably be eliminated if HPV infection became less prevalent.
In the other study, published in the same issue of the journal, researchers at the drug company GlaxoSmithKline, the University of Texas Medical Branch in Galveston, and several other institutions studied the effects of a vaccine against herpes simplex virus type 2 (HSV-2, or genital herpes), which also requires three shots. In women who had neither HSV-2 or HSV-1 (oral herpes) at the outset, the vaccine was about 75 percent effective in preventing infection.
It had little effect on women who had HSV-1 already (perhaps because immune stimulation arising from that infection was partially protective against HSV-2), and none on men.