The role of infectious agents in carcinogenesis

Zurich - With infectious agents such as viruses, parasites and bacterial infections playing a greater role in the induction and maintenance of carcinogenesis, Dr. Harold zur Hausen of Deutsches Krebsforschungszentrum, Heidelberg, Germany, has demonstrated that infectious agents can either directly or indirectly mediate cell transformation.

Dr. zur Hausen talked about the role of viruses in human cancers and the extent viruses and infections, such as bacterial and parasitic infections, play in carcinogenesis at the Skin Care Conference, 2004, here.

"Approximately, 15 to 20 percent of human cancers on a global scale can be linked to these types of infections," Dr. zur Hausen says. "Specifically, infections including Epstein Barr virus (EBV), human papillomaviruses (HPV), hepatitis B and C viruses, human herpesvirus type 8, human T-lymphotropic retrovirus (HTLV1), Helicobacter pylori and parasites play a major role."

"What I mean by directly engaged in cancer development is the expression of specific oncogenes, for instance by Epstein Barr virsus or human papillomaviruses, where the expression of the viral oncogenes is necessary for maintaining the transformed phenotype of the respective types of cancer cells. So, in cervical cancer, for instance, if you block the transcription of the viral oncogenes the cells revert to a quasi normal state or undergo apoptosis," Dr. zur Hausen explains.

Oncogenes' role Viral oncogenes not only play a role in the induction of carcinogenesis but the maintenance as well.

"These viruses have oncogenes themselves," he says. "They contain an exogenous oncogene, which is brought into the cell. In the case of the human papillomaviruses, the E6 and E7 genes need to be expressed in order to maintain the malignant state of the cell, so they are directly engaged in the process of carcinogenesis but also the maintenance of the carcinoma state. In all likelihood, this is also true for the human herpesvirus type 8 in Kaposi's sarcomas and also for human T-lymphotropic retrovirus (HTLV1)."

More recently, the induction of cancers by immunosuppression, indirect modes of carcinogenesis by infectious agents, have become more evident.

"The most famous example is the HIV virus where immunosuppression mediates the emergence of other types of tumors frequently linked to viral infections, like Epstein Barr virus. The HIV agent indirectly contributes to cancer," Dr. zur Hausen tells Dermatology Times.

With both direct and indirect onset of carcinogenesis, Dr. zur Hausen says the virus by itself is not sufficient, it may be necessary but not sufficient and additional modifications of specific genes may be needed. These modifications are either mediated by specific functions of viral oncogenes or in other cases may be due to mutations in DNA, which occur by chemical or physical mutagens.

Dr. zur Hausen comments, "In all these cases, cellular genes need to be knocked out to permit an unrestricted expression of these specific viral oncogenes. Intracellular control existing in these cases, which basically prohibits the virus carrying cell becomes a cancer cell and this control needs to be interrupted and that only happens by mutation events."

Cancer prevention The identification of infectious agents has become more and more important as vaccines are available to prevent the onset of carcinogenesis or at least limit the possibility of cell transformation.

Dr. zur Hausen notes two examples of cancer promoting factors that, with vaccination, could potentially reduce the risk of carcinogenesis.