A Vaccine for Cancer?

Michelle A. Ozbun, UNM College of Medicine
Rebecca Hartley, UNM College of Medicine
 

Everyone knows that cancer is a horrible disease. The American Cancer Society reports 12 million new cases worldwide in 2007, with 7.6 million people dying from malignancies. But did you know that nearly 20% of cancer cases are attributed to infections with viruses or bacteria? This may be an under-estimate because there may be even more infectious diseases that contribute without our knowledge-this could be from organisms we know about AND those we have yet to discover!
 
Some examples of infection-associated cancers include nasopharyngeal (nose and throat) carcinoma, non-Hodgkin's lymphoma, Kaposi's sarcoma, liver cancer, gastric (stomach) cancer, and adult T-cell leukemia. The cancer with the strongest link to infection is cervical cancer, with human papilloma virus (HPV) infections causing more than 99% of cervical cancers. HPVs also cause other cancers of the genital tract, and some of the head-and-neck region. There is even evidence that certain HPVs might be involved in skin and breast cancers!
 
The word "papilloma" is Latin for "wart," and a wart is technically a skin tumor, it's an abnormal growth. HPVs cause nearly all skin warts. There are over 100 different types of HPVs, and different types cause warts on different parts of the body. Some HPVs cause only hand warts, some only foot warts, some only genital warts. Hand warts, for example, cannot be transmitted to the foot or to the genital types of skin. Importantly, not all tumors are cancerous, and only a few HPV warts turn into cancers. Although any abnormal cellular growth is a tumor, only when it can spread to other organs, or become "metastatic," does it officially become a cancer. It's usually the spread of the tumor to key body systems (brain, lungs, liver) that causes death.
 
Cancer arises typically later in life due to a series of DNA mutations in a cell that provide that cell with an increasing growth advantage over the cells around it. Generally, cells in our bodies can divide in a controlled fashion as needed, and the balance of programmed cell death ("apoptosis") in the same tissues keeps the average number of cells in our bodies constant. This can be called homeostasis. Tumors arise when this balance becomes disrupted, either because cell division increases or because cell death decreases. So, if a cell gains a DNA mutation that causes it to divide faster, or prevents it from dying when it should, it gains a growth advantage, and it can then gain another mutation, and another. If the cells fails to die, a tumor will arise. Mathematicians have calculated that a cell needs only to gain five DNA mutations in key growth promoting genes in order to cause cancer. Luckily, this does not happen very often. Our cells and our immune system are pretty good at maintaining cell growth in balance and keeping us healthy.
 
Some viruses that cause cancer do so because when they infect a cell they cause the cell to divide more rapidly, and then prevent it from dying. They don't do this to deliberately cause cancer; the viruses do this so they can carry out their "prime directive" - to make more viruses and permit their spread to new cells or to a new animal. Usually the cancer arises only as an accident, because the virus may push the infected cell to divide too rapidly, and mutations may arise during the increased cell division.
 
It's important to note that virus infections rarely cause cancer. For the most part our bodies keep infections in check, and only if those extra DNA mutations arise will a tumor progress to a cancer. For example, HPV infections in the epithelial (skin) cells of the genital tract are the most common sexually transmitted infections in the US, but only a handful of people will develop cancer from HPV infections. There are more than 5.5 million new genital HPV infections reported every year, and more than 20 million sexually active people (men and women) are currently infected with genital HPVs. In contrast, there are less than 5000 cases of cervical cancer per year.
 
Low cervical cancer death rates in the US are due to the fact that we have effective, but quite expensive, screening programs. Sexually active women are urged to have a yearly exam, wherein a Pap test is performed. This test samples cervical cells to determine if pre-cancerous or cancerous cells are present. Like most cancers, cervical cancer recovery is excellent if the cancer is caught early. However, in less developed countries, the death toll from cervical cancers is much higher. Worldwide, there are about 500,000 new cases of cervical cancer a year, and 290,000 deaths. Most of the cases and most of the deaths occur in poor countries where women do not have regular Pap tests.
 
You might be saying to yourself, "If some cancers are caused by infections, couldn't we prevent those cancers by eliminating the infectious that cause them?" You are absolutely right! And that is exactly the thinking behind the new HPV vaccines Gardasil® and Cerviarix® marketed as "Cervical Cancer Vaccines."
 
The HPV vaccine is made up of four HPV types, two that cause 70% of cervical and other genital cancers, and two that cause benign genital warts. The vaccine is given in three doses over 6 months time and is not infectious. The vaccine contains only the outside protein coats of the viruses that will cause the immune system to make antibodies, which can prevent future infections. We call these neutralizing antibodies, because they neutralize and prevent infections. Studies in the last five years have shown that this vaccine is safe and is almost 100% effective in preventing infections by the four HPV types in the vaccine, and the vaccine prevents genital warts and pre-cancers by these viruses too. Although, we have not followed vaccinated women long enough to determine that cancer incidences will decrease, the lower infections suggest that this will occur.
 
This vaccine has great promise! However, Pap screening in women is still essential, even if all susceptible people were to be vaccinated. This is because there are other HPV types not in the vaccine that can cause 30% of cervical cancers, and because we don't yet know how long the protection will last. The vaccine also may require a booster after five or so years. During the Café, we will also discuss important issues, including the cost of the vaccine, who should be vaccinated, and whether the vaccine will reach those who need it most. We will talk about some roadblocks to vaccination and some of the current research aimed at making more effective and easier use of vaccines.