Cancer Viruses

You've probably seen the commercial. It's set in a park, or perhaps a particularly nice college campus. A number of concerned women are telling you that they just learned that cervical cancer is caused by a virus, human papilloma virus, or HPV. The commercial is for a new vaccine against HPV.

Getting infected by HPV can indeed lead to developing cervical cancer. HPV is also thought to play a role in the development of other cancers, including some cancers of the vulva, anus, penis, head, and neck.

In addition to HPV, there are several other viruses that are known or believed to cause certain cancers. Epstein Barr Virus, the Hepatitis B and C viruses, and Kaposi Sarcoma associated herpesvirus are some of the better studied cancer viruses. Worldwide, viruses may be responsible for about 15% of cancers. That figure tends to be higher in developing countries and lower in industrialized ones.

We'll take a more detailed look at HPV and some other specific cancer viruses in a moment. First, some background on viruses and cancer in general...

What is a virus?

Viruses have many of the characteristics of living things, but not all of them. Like living things, viruses have genes and proteins and can evolve. However, they cannot reproduce on their own. Instead, they must infect living things. When a virus infects a living cell, it takes over the cell's machinery and causes it to produce more virus particles instead of functioning as it normally should. Usually, viruses reproduce quickly, causing the cells they infect to burst. Some viruses, called lentiviruses, can stay dormant for a period of time, however. In some cases, like that of the human immunodeficiency virus (HIV), they may be dormant for years. There are viruses that infect every living thing, from bacteria to plants to people.

Cancer and the Cell Cycle

Normally, the cells of the body are organized into tissues, or groups of similar cells with specific functions. Different tissues reproduce at different rates. Skin reproduces quickly, while nerve cells usually stop reproducing during adolescence. In cancer, abnormal cells reproduce when they shouldn't and invade or attack other tissues. Benign tumors also reproduce when they shouldn't but don't attack other tissues. Both benign and malignant tumors can grow either quickly or slowly. The abnormal behavior of cancerous cells has to do with mistakes in the cell cycle.

The cell cycle is the process by which cells reproduce. There are four phases to the cell cycle. During the first phase, the cell grows larger. During the second phase, the cell makes a copy of all its DNA, which contains its genes. The cell grows a bit more during phase three. Finally, in the fourth phase, the cell divides. Each new cell gets a complete set of DNA, which was copied in phase two.

Each of the four phases has several steps, including checkpoints to make sure that everything is going according to plan. Many of the checkpoints have to do with whether or not the cell's DNA is in good shape. If the DNA is not too badly damaged, the cell cycle may stop or slow down temporarily while the DNA is repaired. At that time, the cell makes particular DNA repair proteins, which get to work patching things up like a road crew doing highway work (only much faster).

The cells in cancer are usually a genetic mess. Sometimes individual genes are changed (mutated). There may be extra copies of genes, or genes may be missing completely. Often, entire chromosomes—the chunks into which DNA is organized—can be broken. The result is that the cell does not behave as it should. Normally, a cell with this kind of genetic damage would go through something called apoptosis. In apoptosis, the cell self-destructs in an organized fashion, similar to the controlled explosions used to demolish buildings in crowded areas.

Eventually, some cells stop going through the cell cycle. Nerve cells do this early on. Other cells do this when they reach old age, or senescence. Cells don't get wrinkles or age spots, but you can sometimes tell their age by looking at their chromosomes. In bacteria, the chromosome is a circle, but in humans, the chromosome is one long piece of DNA that has a middle and two ends.

The ends are called telomeres (telo- means far and -mere means portion). In most cells, the telomeres wear down. After a while, the telomeres wear down too much and the cell can no longer reproduce. Some cells, however, have an enzyme called telomerase that builds these ends back up. All cells have the ability to make telomerase, but usually only stem cells do.

Cancer interferes with the safeguards that keep cells healthy: the DNA status checkpoints, the DNA repair proteins, apoptosis, and the shrinking telomeres. Just how the safeguards are taken down can vary.

Human Papilloma Virus

As mentioned above, HPV infection can lead to a number of different tumors. There are over 100 types of HPV, which are assigned numbers. HPV is usually transmitted sexually, and a person can become infected by more than one type of HPV at the same time. Not all of the strains are cancer-causing. For example, some types of HPV cause genital warts. Cervical cancer can be caused by types 16, 18, and at least 30 others. Type 16, however, is responsible for about half the cases of cervical cancer. The new HPV vaccine is effective against type 16 as well as types 6, 11, and 18.

HPV makes two proteins that interfere with the normal cell cycle. One of them increases the activity of the telomerase and also prevents the proteins involved in apoptosis from doing their job. As a result the cell lives longer and reproduced more than it should. Both the proteins prevent the cell from dividing its chromosomes appropriately, so the DNA in these cells is damaged.

Screening for cervical cancer has been effective in industrialized countries at reducing the number of new cases of cervical cancer and the number of deaths from cervical cancer. However, 80% of cervical cancer cases occur in the developing world, where screening can be difficult.

Other Cancer Viruses

Some of the other viruses that can cause cancer are the Epstein Barr Virus, Kaposi's Sarcoma-associated Herpesvirus (also called human herpesvirus 8), and the Hepatitis B and Hepatitis C viruses.

Epstein Barr Virus, a type of herpesvirus, was the first virus to be linked to a human cancer: Burkitt lymphoma. In Africa, where the Epstein Barr Virus is widespread, 90% of the cases of Burkitt lymphoma are associated with the virus. In the US, only 20% of the cases of Burkitt lymphoma are. Infection with malaria seems to increase the chances of developing cancer from an infection of Epstein Barr Virus. The virus is also linked to cancers of the nose and upper airway and Hodgkin's Disease.

Kaposi's Sarcoma-associated Herpesvirus typically doesn't cause symptoms in healthy people. Kaposi's Sarcoma was first seen in elderly Mediteranean men. Since the 1980s, it has become one of the characteristic features of AIDS. Organ transplant recipients also may develop Kaposi's Sarcoma because of the drugs they take to suppress their immune systems.

There are at least eight types of hepatitis viruses, but only Hepatitis B and C are linked to cancer, specifically of the liver. The two viruses are not closely related. Hepatitis C is the most common cause of hepatocellular cancer after alcohol. About 1-4% of people who are infected with Hepatitis C eventually develop cancer. There is no vaccine for the Hepatitis C Virus, but there is one for the Hepatitis B Virus.

It's not yet clear exactly how some of these viruses cause cancer. Most seem to mess with the normal workings of the cell cycle and the cell's ability to control its DNA. In the future other cancer viruses may be discovered, but even if they aren't, cancer viruses have already taught us much about the normal, and sometimes abnormal, workings of our own cells.