A couple of years ago, I contributed to a documentary with the intriguing title Catching Cancer. We don’t normally regard cancer as an infection, so it often comes as a surprise to learn that more than 20% of the global cancer burden can be attributed to infections, and that most of these infections are viruses.
To understand this link, we first need a basic understanding of cancer.
What is cancer?
Put most simply, cancer is a collection of cells that have lost their way. Each cell in our body is a machine programmed by the genetic information it contains to perform a specific job. A cancer cell has a corrupted program, with several genes that have acquired mistakes.
Each cell in our body has (approximately) the same genetic information, and passes this on to daughter cells when it divides. Any cell in our body is programmed to use only a subset of that information, which tells the cell whether to be part of your skin, your brain or your blood.
Much of that programming tells the cell what to do when the environment changes. It might be instructed to produce a protein (such as insulin), to divide, to repair itself, or to die. This programing is generally directed by signals from outside the cell.
A cancer cell will have programming mistakes which stop it responding correctly to external directions. The cancer cell will divide inappropriately, lose its specialist function, and become able to move to places it shouldn’t.
Genetic mistakes, once they have arisen, are passed on to the daughter cells, and eventually, the body’s ability to sort the problem fails. When there are enough misbehaving cells present, we recognise this as a cancer.
Where do viruses come in to the picture?
Viruses are not cells, but they infect cells, and have genes that can program the infected cell to make more viruses. To do this efficiently, some viruses instruct an infected cell not to die when it should, but to divide and produce more (infected) daughter cells.
Not all viruses do this: most simply multiply inside the cell and then cause the cell to die, releasing viruses to infect more cells.
But for those viruses that reprogram the cell not to die, the longer the cell lives, and the more daughter cells it gives rise to, the more viruses are produced, and the more successful the virus becomes.
The human papillomavirus that I study behaves like this. That’s why some of them give us warts, which are little mounds of excess skin cells, each acting as a virus factory. But warts are not cancers, so how can some papillomaviruses cause cancer?
Cells have defence mechanisms against viruses – part of the cell’s machinery can tell when the cell is dividing inappropriately, or when stray viral genes are hijacking the cell machinery. Usually these defences cause the cell to die if they detect trouble. But some viruses have acquired the ability to reprogram the cell machinery to overcome these defences, and, in doing so, they set the cell up for trouble.
Mistakes in our cells’ genes occur quite commonly when our cells divide – there’s a lot of information and the machinery which copies it isn’t perfect. So the cell defences that recognise viruses are part of the machinery that recognises mistakes in the cells’ genes. If the cell finds a serious genetic mistake and can’t fix the problem it dies, rather than dividing.
If a virus has switched off the defences against viruses and genetic mistakes, the cell can divide with mistakes in the gene. These mistakes occur quite commonly if the cell is dividing, and if enough mistakes accumulate that reprogram the cell, the cell can acquire the behaviours of a cancer cell: dividing when it shouldn’t and going where it shouldn’t.
Which viruses cause cancer?
The viruses we recognise as causing cancer include some strains of papillomavirus, two hepatitis viruses (B and C), the glandular fever virus Epstein Barr virus, and some polyoma viruses.
But most people who catch them don’t develop cancers. Even a persisting viral infection such as papillomavirus doesn’t cause a cancer in everyone infected. Through sexual activity, most of us will get infected with the genital papillomaviruses that can cause cancer. Fortunately, most of us get rid of them between 12 months to five years later without even knowing we’ve had the infection.
Even if the infection persists, only a few individuals accumulate enough genetic mistakes in the virus-infected cell for these to acquire the properties of cancer cells.
Cancer-causing viruses are more likely to persist if the immune system is faulty and can’t eliminate them. This can occur, for example, in patients taking immune-suppressive drugs to control autoimmunity or prevent transplant rejection, and in patients with HIV AIDS. In consequence, virus-associated cancers become more common with immune suppression.
This information gives us a clue as to where to look for other virus-causing cancers – if a cancer becomes more common if your immune system is damaged, then maybe a virus is contributing to the risk.
One place we’re looking at the moment is in the skin, because the common squamous skin cancer becomes 30 to 100 times more common with immune suppression. We know that sun damage to the skin is the major cause of the squamous skin cancer, but we suspect a virus or viruses may also contribute to the risk.
Vaccinating against cancer
We have effective vaccines to prevent infection with some viruses. Vaccines against hepatitis B and papillomavirus, for instance, have reduced the burden of cancer caused by these viruses.
So finding a virus in skin cancers should enable development of a vaccine that would help reduce the burden of this extremely common disease, which affects one in three Australians in their lifetime, and costs more to prevent and treat than any other single cancer type.
It took 25 years from discovery of the papillomavirus, and 15 years from discovery of the vaccine technology, before there was a vaccine to help prevent cervical cancer, which kills over 250,000 women world wide every year. Now, we need to make sure it’s used globally, to prevent this second most common cause of cancer death in women.
Vaccines are the public health measure that, after safe food and water, have saved most lives. Vaccines for the cancers we know or suspect may be linked to viruses should be possible. We know how to do the work. All it will take is funding to support the research scientists working on these vaccines, and time.
How long are you prepared to wait for that shot?