Connecting viruses to cancer: how research moves from association to causation.

In the past two decades, the study of viruses has contributed greatly to the understanding of cancer biology. But determining that a virus is a cause or a co-factor in cancer is another story, and it is slow, difficult work. " As tools of discovery, viruses have turned out to be a Rosetta Stone for unlocking the mysteries of cell growth control, " said Janet Butel, Ph.D., professor of virology and chairman of the department of molecular virology and microbiology at the Baylor School of Medicine in Houston. Although about 15% of all human tumors worldwide are caused by viruses, there are only five viruses that have been incontrovertibly established as causing cancer, with numerous others under investigation. Key to proving causation is the fulfillment of a set of criteria, some of which are difficult to prove. Although this area is active, with new research published monthly, it is also fraught with contention and bias, say some virologists. The bar that must be reached to prove a causal link between a virus and a cancer is high—some say too high—and this research has been difficult to finance, a number of researchers said. " While there are constantly attempts to identify novel associations, like all work that breaks new ground, this work is not easily fundable, " acknowledged Charles Rabkin, M.D., of the Viral Epidemiology Branch at the National Cancer Institute. " There are different routes to proving causality; it takes time to accumulate a body of persuasive data, and there will always be a variety of studies collected with conflicting results, " said Butel, who is researching the connection between simian virus 40 (SV40) and human brain cancer. But finding virus–cancer connections is more than an academic exercise. " The potential pay-offs of finding virus– human cancer links are new ways of diagnosis, treatment, and even prevention , " said Butel. If an infectious agent is isolated as a major cause, it may be possible to develop a vaccine to prevent disease. The hepatitis B vaccine has been used now for more than 15 years, and vaccines against human papillomavirus (HPV) are in clinical trials for the prevention of cervical cancer. At present, accepted causal associations between viruses and human cancer are HPV and cervical cancer; human T-lymphotrophic virus type-1 (HTLV-1) and adult T-cell leukemia and lymphoma; hepatitis B and C and liver cancer, Epstein–Barr virus (EBV) and nasopha-ryngeal cancer, …