The Department of Health and Human Services has for the first time included viruses on the federal government's official list of agents that cause cancer in people.

The hepatitis B and C viruses, which cause cancer of the liver, and the human papillomavirus (HPV), which causes cervical and anal cancers, are listed along with 55 other "known" human carcinogens, including asbestos, tobacco smoke, and ultraviolet radiation.

The list was published January 31 in the National Toxicology Program's (NTP) Report on Carcinogens, now in its 11th edition. This biennial report for the National Institute of Environmental Health Sciences historically has focused on the toxins that people might encounter in their homes or workplaces. But the editors of the last two editions broadened the scope to include more than just harmful chemicals.

"The report was originally requested by Congress to provide a public document that informs people of the causes of cancer in their everyday lives," explained NTP Associate Director Dr. Christopher Portier. "Viruses are one such cause, and we felt it was important to include them in the report."

Although a number of viruses have been linked to cancer, the evidence is strongest for the three in the report. Their inclusion will likely surprise no one in the field.

Dr. Thomas O'Brien of NCI's Division of Cancer Epidemiology and Genetics welcomed the addition of viruses to the list. "Viruses are among the strongest carcinogens that are known," he said. "They cause a variety of cancers, such as liver cancer, which is one of the most prevalent worldwide."

More than 80 percent of the world's cases of liver cancer are attributable to infection by the hepatitis B and C viruses, and some 350 million people are chronically infected with one of the seven subtypes of the hepatitis B virus (HBV). Chronic infections and those that occurred during early childhood are particularly strong risk factors for the major form of liver cancer known as hepatocellular carcinoma, which is usually untreatable and fatal.

The good news about discovering links between viruses and cancer is that it becomes possible, at least in theory, to prevent cancers through vaccines and the surveillance of viruses. The HBV vaccine offers an example.

When the vaccine was developed years ago, hepatocellular carcinoma became the first cancer that could largely be prevented through vaccinations and the screening of blood and blood products for viruses. Rates of cancer due to HBV infection have decreased in those countries that have large-scale vaccination programs, although the rates for liver cancer associated with the hepatitis C virus (HCV) in particular have risen in the United States.

Over the next 50 years, deaths from liver cancer can be reduced if universal HBV vaccination programs are implemented around the world, according to Dr. James Goedert of NCI's Viral Epidemiology Branch. In a commentary in the February 16 Journal of the National Cancer Institute, he stresses the need for programs that can reach infants in rural areas of Africa, Asia, and South America, where mortality from hepatocellular carcinoma is 20 times higher than in the United States.

In an interview, Dr. Goedert identified two other viruses he feels are worthy of inclusion in NTP's report: HTLV1, which causes adult T-cell leukemias, and human herpesvirus 8 (HHV8), which causes Kaposi's sarcoma and primary effusion lymphomas. HIV, the Epstein-Barr virus, and the bacterium Helicobacter pylori have also been linked to cancers.

"From a public health perspective, it's important to look at these viruses very closely because there's reason to believe they're responsible for a lot of cancers worldwide," said Dr. Eric Engels of NCI's Viral Epidemiology Branch, who has studied a range of viruses, including HIV and HHV8, both linked in some way to cancer.

Dr. Engels is also investigating HCV in tumors other than liver cancer, such as non-Hodgkin's lymphoma (NHL). HCV infection is twice as common in people with NHL compared with people from the general U.S. population, his team reported in the International Journal of Cancer in March 2004.

Experimental vaccines have been developed against forms of HPV that cause cervical cancer, one of the most common among women. The virus is found in most women treated for cervical cancer, though infection does not always lead to the disease.

As noted in the November 30, 2004 NCI Cancer Bulletin, NCI researchers have launched a phase III clinical trial in Costa Rica to test an HPV vaccine.

By Edward R. Winstead