Known cancer-causing pathogens: the tip of the iceberg?
At the end of the 19th century the Scottish pathologist William Russell published an article in The Lancet titled ‘The Parasite of Cancer’ [The Lancet 1899; 3984: 1138-1141]. The response by the physicians of the day ranged from scepticism to sheer disbelief, largely because cancer is considered to be a non-communicable disease. With the exception of a few eccentric scientists, this incredulity persisted into the latter half of the 20th century, when the discovery of the Epstein-Barr virus from Burkitt lymphoma cells in 1964 led to recognition that there may be a few cancer-causing viruses. However in the last fifty years there has been a steady increase in the number of infectious agents found to cause cancer, and in May this year a relevant article was published in The Lancet Oncology. The authors used data from 2008 and found that of the 12.7 million new cancer cases occurring in that year, around two million were caused by infectious agents.
The cancer-causing microbes discovered so far include viruses, bacteria and parasites. Currently hepatitis B and C viruses, which can cause hepatocellular carcinoma, human papilloma viruses, strains of which are the aetiological agents of cervical cancer, and the bacterium Helicobacter pylori, which can cause gastric cancer, are considered to account for more than 80% of the cancers caused by infectious agents. Other carcinogenic viruses discovered so far include human T-lymphotropic virus, Kaposi’s sarcoma-associated herpes virus and Merkel cell polyomavirus. Well established bacterial associations with cancer include Salmonella typhi and gallbladder/hepatobiliary carcinoma and Chlamydia pneumoniae and lung carcinoma. In addition there is evidence for the association of Streptococcus bovis and colorectal cancer. There are also some established relationships between parasitic infections and cancer. The association of long-term infection with the parasitic fluke Schistosoma haematobium and bladder cancer is well documented, as is the association of long-term infection with the Far Eastern liver fluke Opisthorchis viverrini and cholangiocarcinoma. Some evidence also links the common protozoan parasites Crytosporidium parvum to gastrointestinal cancer and Toxoplasma gondii to the development of brain tumours.
All these organisms are able to evade the host’s immune system and establish persistent infections of many years’ duration, ultimately initiating abnormal cell growth followed by tumour development. So couldn’t efforts to lighten the global burden of cancer put more emphasis on timely diagnosis of these infections followed by suitable therapy, or even better the development and widespread use of effective vaccines? And whilst there isn’t a single ‘parasite of cancer’, it is likely that there are many other cancer-causing pathogens to uncover!