Can a virus cause cancer in humans?
In a word, yes. In fact, at this point multiple viruses have been identified as playing a role in the progression of many different cancers. The very first of these cancer-causing viruses was discovered by Peyton Rous in 1911, making the field of tumor virology over one century old. While this initial discovery was a virus that causes tumors in chickens, many important human cancers have since been discovered to have a viral component. The first human tumor virus to be discovered was Epstein-Barr virus (EBV) in association with Burkitt’s lymphoma in 1965 (see featured image). Since then many more viruses have been found to be tumorigenic (tumor-causing) in humans and more may still be awaiting to be discovered.
How is it that these many different viruses are involved in so many different types of cancers? What about these viruses makes them tumorigenic?
One first thing to notice about the viruses that are involved in the development of cancer is that they all involve DNA at some phase in the replication of their genomes. Not all are DNA viruses however, retroviruses such as human T-cell leukemia virus type 1 (HTLV-1) are known to be involved in oncogenesis and have RNA genomes. However, these viruses do have a DNA intermediate during their replicative cycle. The fact that these viruses involve DNA in their replicative cycle means that they have the opportunity to interact and integrate with our own cellular DNA. This interaction with our own DNA can have multiple negative consequences depending upon which cellular function it disrupts. The integration of viral DNA into our genomes can disrupt the expression of important genes in two ways. It can function to activate cellular proto-oncogenes that support the development of tumors or it may inactivate important tumor suppressor genes. Both of these functions allow further dangerous mutations to occur that contribute to oncogenesis.
Outside of disrupting normal host gene expression through genomic disruption some viruses also encode oncogenic proteins that can bind to and inactivate important cellular tumor suppresor proteins. The human papilloma virus (HPV) encodes an oncoprotein E6 that inactivates p53, a critical tumor suppressor protein. By inactivating this protein HPV is able to drive cellular proliferation. This is actually beneficial for the virus as it utilizes host machinery to replicate its own genome. In fact, it is important to remember that these viruses are not so much directing the development of cancer, but instead that the long term presence of these viruses and their associated proteins in the cell may contribute to an environment that is beneficial to the virus but drives the cell towards becoming cancerous as well. The goal is not to cause cancer, simply to replicate in the most efficient way possible; the development of cancer secondary to productive infection.
Also, these viruses are those that chronically infect their hosts such as HPV or hepatitis B virus (HBV). One theme that emerges with virally-induced cancers is that they take time. Time is necessary for dangerous mutations to occur in such abundance that the cell transforms into cancer. It takes multiple key mutations before cells become cancerous, all of which can result in pre-cancerous changes that can be identified by medical professionals such as pathologists. This is why early screenings for cancers such cervical cancer are so critical; early detection of these pre-cancerous lesions can be used inform treatment and remove the suspect tissue before it develops into cancer and potentially metastasizes to other sites in the body. This approach has proven to be effective with cervical cancer in the United States*. Death rates from this disease have gone down in this country as regular screenings for pre-cancerous lesions have been instated. Further screening for other virally-induced cancers is key. Recently the CDC has released recommendations the that the Boomer Generation in the United States all be tested for Hepatitis C virus, the causative agent of some liver cancers. By screening this population now before the development of long-term sequelae it is possible to intervene and treat the infection, thereby reducing the downstream health care costs. It is much easier to treat a patient with the current HCV protocol as opposed to finding liver donors and awaiting transplantation.
Thankfully, we are in the beginning of an era wherein we have not only begun to identify viruses involved with the development of cancer, but to develop vaccines against these specific strains as well. None of these vaccines are more famous than the new HPV vaccines that are offered to both boys and girls in the US. This vaccine protects against the strains most closely associated with the development of cancers and warts and is a valuable tool in reducing HPV-induced cancers. However, this benefit will not be seen immediately, as once again virally induced cancers take time to develop. Despite this lag in time between vaccination and disease-prevention it cannot be understated how valuable these new tools are for us and how important it is that this research continues unabated.
*The human cost of cervical cancer was skillfully captured by Rebecca Skloot in The Immortal Life of Henrietta Lacks, and these HPV infected cancer-cells have become the cornerstone of modern science.
[Image credit Wikipedia Commons used under creative commons license.]