Ten years ago many researchers had all but abandoned their theory that cancer is caused by viruses. Throughout much of the 1960s that theory had drawn hundreds of scientists into a widespread search for a cancer virus, but by the early 1970s their hopes had been eroded by the failure to turn up a single unequivocal case of human cancer caused by a virus.
Now, according to a score of reports at a major international conference here last week, the tide has turned again.
Evidence has been found that at least four kinds of human cancer have been caused by viruses -- cancer of the uterine cervix, liver cancer, a rare form of adult leukemia and nasopharyngeal cancer, which is rare in the economically developed world but a major killer in China and Africa. In the United States, viruses are estimated to cause about 4 percent of cancers.
Although it has been established that viruses are necessary to cause these cancers, there is much evidence that they do not act alone. Other factors, ranging from other diseases to genetic susceptibility, seem to be necessary as well.
"Cancer virology has certainly come of age," Dr. Peter J. Fischinger, deputy director of the National Cancer Institute, told the conference. Fischinger, whose agency was a cosponsor of the meeting, said that despite the pessimism that once dimmed hopes of finding human cancer viruses, the search "was never deemphasized" at the agency. In 1985, he said, NCI spent $135 million on cancer virus research.
Jacques Crozemarie, head of France's Association for Cancer Research, the other cosponsor, said it is estimated that in some parts of the world, especially the underdeveloped tropics, up to half of all cancers "could well be associated with viruses."
Curiously, all four of the known viral cancers are caused by viruses that are transmitted chiefly by sexual intercourse.
In the United States, the most prominent of these is cervical cancer, the fifth most common cancer of women. The disease, which causes nearly 7,000 deaths each year in the United States, has been proven to be caused by the same virus that more commonly causes genital warts, the papilloma virus.
There are several varieties of the papilloma virus, and some scientists presented preliminary evidence that each produces a different kind of cervical cancer. The differences could guide doctors toward the treatments, chiefly different forms of surgery, best suited to each type of the cancer. More than 90 percent of cervical cancers examined in one study contained the virus.
Gerard Orth of France's Pasteur Institute reported a link between the papilloma virus and certain potentially precancerous conditions of the cervix. For example, the cervical cells of up to 20 percent of women who have dysplasia, or abnormal growth, of the cervix contain the virus. Because dysplasia sometimes progresses to cancer, detection of the virus at this early stage could reveal which dysplasias are most likely to turn cancerous.
Certain forms of the papilloma virus have also been linked to relatively rare tumors of the penis, vulva and mouth. Other forms of the virus cause ordinary skin warts, which are slow growing and have never been found to turn malignant.
Nasopharyngeal cancer, which afflicts the nose and upper throat, is a major killer in large parts of China and sub-Saharan Africa. In some parts of China, according to Y. Zeng of that country's National Center for Preventive Medicine, nasopharyngeal cancer is the third-largest cancer killer of men and the fourth largest of women. It has now been shown to be caused by the long-known Epstein-Barr virus, which has also been linked to a common African cancer of the lymph system called Burkitt's lymphoma.
The Epstein-Barr virus is something of a mystery because in the United States and other industrial countries it is the cause of mononucleosis, a fairly common but nonfatal infection. Nasopharyngeal cancer, on the other hand, is virtually unknown in developed countries except among immigrants from China.
Zeng said Chinese scientists have found that evidence of infection by the virus can be detected as much as five years before a person develops the cancer, a development that could permit unusually early treatment.
A third major viral cancer afflicts the liver and is caused by the hepatitis-B virus, which causes hepatitis. In China, liver cancer ranks from first to fourth as a cancer killer depending on region. It is now clear that people who have recovered from hepatitis-B remain at risk for liver cancer many years afterward. Another form of hepatitis, called hepatitis-A, is caused by a different virus and is not associated with liver cancer.
Because a hepatitis-B vaccine exists, having been developed before the link to cancer was established, liver cancer automatically became the first form of cancer for which there is a vaccine. Because the vaccine is unusually expensive, costing $90 per person, its use is limited to certain high-risk groups, such as homosexual men.
The rarest of the established viral cancers is adult T-cell leukemia, which is caused by a virus called HTLV-1. This virus, discovered by Dr. Robert Gallo of the National Cancer Institute, was the first proven to cause cancer in humans. It is related to the virus that causes AIDS (acquired immune deficiency syndrome), HTLV-3.
The disease has so far been found to be most common in Japan and Jamaica.
Scientists have known for decades that viruses cause various cancers in animals. It was assumed that they must be doing the same in human beings. Now that the early hopes have finally paid off, many cancer virologists expect to find more types of cancer in which viruses are necessary parts of the cause.