Cambridge scientists discover an additional step along the road to cervical cancer
9 March 2006
Cervical cancer is often associated with infection by the wart virus, also known as Human Papillomavirus or HPV. However, only some women infected by the virus will go on to develop cervical cancer. A group led by Dr Nicholas Coleman at the MRC Cancer Cell Unit in Cambridge has discovered a key event that appears to lead to cancer progression in contrast to harmless viral infection.
When cervical cells are infected with HPV, the viral DNA exists as "circles" of DNA called episomes. Earlier work by the Coleman lab showed that the fate of these circles determines when an HPV infection will progress to cancer—that is, when some circles of viral DNA become "integrated"into the cervical cells' own DNA. In their new work, published in PNAS (7 March), the group shows that the remaining circles of viral DNA actually prevent cancer formation and so they need to be eliminated for carcinogenesis to occur. So, it's not only important where some of the circles have gone (episome integration), but also that the remainder have been cleared from the cells (episome loss). Finally, they show that cells with episome loss have an antiviral response. Ironically, this is usually a protective host response which in this case increases the risk of cancer formation.
Currently the cervical smear screening programme detects abnormalities in cervical cells but it is not yet able to determine which of those cells with abnormalities actually reflect a pre-cancerous condition. Identifying episome integration and episome loss as key steps in cancer progression may be a useful basis for secondary tests after an initial result of an abnormality on a cervical smear. These secondary tests may serve to distinguish patients who do in fact need further treatment from the majority who do not.
Dr Nicholas Coleman of the MRC Cancer Cell Unit in Cambridge said “A lot of women have surgery to their cervix that they do not need. Understanding the mechanisms of development of cervical cancer should allow us in the future to introduce tests that are predictive of clinical behaviour. Identifying the importance of loss of episomes is a novel observation which allows us to look at the development of cervical cancer in a new way.”
