Scientist Survivor
Virus Linked to Pediatric Eye Tumor
Center researchers have linked the virus that causes cervical cancer to retinoblastoma, an eye tumor that is one of the most common childhood cancers. But it is the first study showing a connection between human papilloma virus (HPV) and the tumor retinoblastoma, and much more research needs to be done to firmly establish a cause-and-effect relationship. "This discovery may not change the world on a scientific level, but it has the potential to change the lives of many children and hopefully protect them from this disease," said Carlos Cordon-Cardo, Director of MSK's Division of Molecular Pathology and lead author of the study, which was recently published in Clinical Cancer Research.
Retinoblastoma was the first cancer found to have a hereditary component. Scientists isolated the Rb gene, which leads to retinoblastoma when it is mutated, in the late 1980s. (The gene has since been implicated in many other types of cancer.) Retinoblastoma is often treated by removing one or both eyes and can be fatal if left untreated. Although the genetic form of the disease is well understood, until now little was known about what causes the non-familial form.
Several Mexican researchers who had worked in Dr. Cordon-Cardo's lab - and had since returned to Mexico - observed that in certain inner-city hospitals in Mexico City, the incidence of retinoblastoma in young children was much higher than normal. In addition, young women in those areas had a high incidence of HPV infection, a sexually transmitted disease. The researchers decided to test for a link between these two observations. They suspected that children were being exposed to HPV during childbirth and that this virus triggered the development of retinoblastoma.
Dr. Cordon-Cardo's lab obtained samples of retinoblastoma tumor tissue from 39 children who had the non-familial form of the disease. They tested the cells and found that 36 percent of tumors carried HPV 16 or HPV 18, two strains already known to cause cervical cancer. In addition, those tissues that carried the virus had a normal Rb gene. HPV makes two proteins, called E6 and E7, that can lead to cancer by turning off tumor-suppressor proteins. Tumor-suppressor proteins prevent cancer from developing, and when they are turned off cells can multiply out of control. In the case of HPV, E6 and E7 bind to the p53 and pRb tumor-suppressor proteins, respectively, blocking their tumor-suppressor activity.
It's a provocative finding," said Ira Dunkel, an MSKCC pediatric oncologist and expert in retinoblastoma. "It has great potential importance, but much more research needs to be done."
According to Dr. Cordon-Cardo, researchers in developing countries throughout the world already have begun testing their retinoblastoma patients for HPV infection and are confirming the connection he found. But it remains to be seen whether the same relationship will be found in industrialized countries, where HPV infections are much less common. Once HPV is more firmly established as a cause of retinoblastoma, it is possible the disease can be prevented by encouraging women to use barrier methods of contraception that reduce HPV infection and by delivering babies of infected mothers by Caesarean section to prevent spread of the virus.
