The German virologist and cancer researcher Prof. Dr. med. Harald zur Hausen (Heidelberg) is one of three Nobel Prize winners for medicine in 2008. In the early 1980s, he had shown that human papilloma viruses (HPV) cause cervical cancer. The other two award winners are also pioneers in the field of virology: Prof. Dr. rer. nat. Françoise Barré-Sinoussi and Prof. Dr. med. Luc Montagnier received the award for the discovery of the HIV virus.
It was Monday morning at a quarter to eleven when the Karolinska Institute in the German Cancer Research Center reached me, ”Zuren told the German Medical Association (DÄ). At the DKFZ, Zuren was chairman and scientific member of the foundation board until his retirement in 2003. „I knew that I had been proposed for the Nobel Prize many times, this year as well.“ Specifically, he didn’t expect to receive the prize now. „I’m extremely happy about it, especially since I’m no longer the youngest,“ the 72-year-old told the DÄ. „Of course, this honor crowns my research life.“
In plantar warts, for example, HPV particles could be detected by electron microscopy, but not in biopsy material from cervical carcinomas. The reason: in the malignant cells, the viral nucleic acid is integrated into the genome and no particles are released. Zur Hausen used the technique of DNA hybridization to detect HPV in the various types of benign warts including condylomata acuminata and cervical cancer cells. In 1983/84, he was able to confirm another of his hypotheses, which initially raised doubts about his research results: Not all of the more than 100 HPV types discovered in the meantime are capable of causing healthy cells to malignant. For cervical, vulvar, vagina and penile carcinoma, these are mainly HPV 16 and 18. Viral HPV nucleic acid can be detected in almost all cervical carcinomas, 75 percent of these are types 16 and 18, which Hausen also discovered and cloned Has.
Zur Hausen also described the multi-step mechanism from infection with HPV to the conversion of a benign into a malignant cell: After HPV exposure (80 to 90 percent of people become infected with the virus during their sexually active phase of life), the virus replicates and expression of the HPV genome. The infection heals in most, 90 percent of the infected epithelial cells, but in ten percent it develops into pre-malignant precursors (dysplasias), which can also be detected histologically using the PAP test.
If we can ever completely cure cancer: it’s a question I can’t answer. We have a good chance of drastically reducing the incidence of tumors, but what we see now is that the incidence, or occurrence, of cancer is increasing globally. The mortality rate of cancer patients is slightly decreasing, but the increase in incidence is not offset by the decrease in mortality.
There are still many cases coming up every year and if we really want to do something against cancer in the future, we need to stop the increase. We know that there are a number of cancer risk factors that can be avoided. At this time, we also know about 20% of the cancers in which infections are involved. Not only can we effectively immunize patients against these types of cancer, but they can practically eliminate them, particularly hepatitis B (a cause of liver cancer) and human papillomavirus (which Professor Zur Hausen found to be related to cervical cancer) because we have vaccines that are currently available.
We believe we have evidence that at least 30% more cancers are also linked to infectious events. This at least provides the hope that in the near future other methods can be developed that will also lead to long-term protection from those diseases – particularly colon cancer, breast and prostate cancer, where evidence is mounting that specific Infectious events play a role. Recently, we have discovered a completely new class of infectious agents that are originally derived from plasmids. Plasmids are a kind of mini-chromosome of bacteria, which we find in a very large number of colon cancer patients.
These are infections that persist for decades, causing chronic inflammation and these inflammations are actually the cause of oxygen radicals and mutation events in cancer-sensitive cells. We have sequenced all the genomes (plasmids) that we have identified so far, and what emerged was really a surprise for us, because they do not represent viral or bacterial sequences.
They are slightly modified bacterial plasmids, originating from specific bacteria but have learned to replicate independently in cattle and human cells. We can show that they are found in inflammatory lesions of the colon, breast and prostate. So, in my opinion, this allows new approaches for prevention and, in the long term, for the treatment of these very common types of tumors.
The biggest challenge is to develop more basic research and put more emphasis on preventive measures to block the incidence of cancer, avoiding cancer precursor lesions with surgical interventions. We need to improve the treatment protocol for cancer treatment. And we need to develop a methodology to achieve long-term protection of patients throughout life.