The term “precancerous cells” is scary. It’s important to begin talking about these cells by saying that not all precancerous cells turn into cancer. In fact, most do not.
Many people have heard of precancerous cells of the uterine cervix that are found during Pap smears, but precancerous cells can occur in nearly any region of the body: the bronchi, the skin, the breasts, the colon, and more. Let’s begin by describing what these cells are, and how they differ from “normal” cells in our bodies.
What are Precancerous Cells?Precancerous cells (also called premalignant cells) are defined as abnormal cells that could possibly turn into cancerous cells, but which by themselves are not invasive.
The concept of precancerous cells is confusing, because it isn’t a black-and-white issue. In general, cells don’t go from normal on day one, to premalignant on day two, and then on to cancer on day three. Sometimes precancerous cells progress to cancer, but more often they do not. They may stay the same — that is, remain abnormal but not invasive — or they may even become normal again.
This last comment is something relatively new to cancer researchers. In the past, it was believed “the damage was done” when a cell was transformed to precancerous by carcinogens in the environment. We are now learning (in a field called epigenetics) that our cells are more resilient than that, and factors in our environment (whether carcinogens, hormones, or even perhaps stress) work together to determine what direction abnormal changes in a cell may go.
It’s important to emphasize again that cells that are precancerous are not cancer cells. This means that, left alone, they're not invasive — that is, they will not spread to other regions of the body. They are simply abnormal cells that could, in time, undergo changes that would transform them into cancer cells.
Another point of confusion is that cancer cells and precancerous cells can co-exist. As an example, in some people diagnosed with breast cancer, there are other regions in the breasts and even in the tumor itself in which precancerous cells are found as well. In many tumors, both malignant and premalignant cells are found.
Degrees of Dysplasia (Precancerous) ChangesThe word dysplasia is often used synonymously with precancerous cells, yet there are a few differences. When doctors speak of dysplasia, they are speaking of abnormal cells that could become cancerous. But in some cases, the words severe dysplasia are used to describe cells that are already cancerous but contained within the tissues in which they began — something known as carcinoma in-situ.
Precancerous changes are usually described in degrees or levels of abnormalities. There are two primary ways that these are described: severity and grade.
- Mild dysplasia – Mild dysplasia refers to cells that are just slightly abnormal. These cells do not usually progress to cancer.
- Moderate dysplasia – These cells are moderately abnormal and have a higher risk of developing into cancer.
- Severe dysplasia – This is the most extreme abnormality seen before a cell would be described as cancerous. Severe dysplasia is much more likely to progress to cancer.
An example that might make this clearer is the cervical dysplasia found on some Pap smears. Cells that are mildly dysplastic rarely become cancerous. On the other hand, if left untreated, severe dysplasia found on a pap smear will progress to cancer 30 – 50% of the time.
There is confusion regarding where exactly to draw the line between severe dysplasia and carcinoma in situ. Carcinoma in situ is a term literally translated as “cancer in place.” These are cancerous cells that have not yet broken through what is known as the basement membrane.
GradesAnother way to describe the severity of precancerous changes in cells is by grades. With cervical cells, these classifications are usually used when a biopsy is done after finding dysplasia on a pap smear.
- Low-grade dysplasia – Low grade changes are unlikely to progress to cancer.
- High-grade dysplasia – Cells with high grade dysplasia are much more likely to progress to cancer.
An example of this would be low-grade dysplasia seen on a biopsy of the cervix. The likelihood of these changes progressing to cancer is fairly low. In contrast, high-grade colon dysplasia associated with colon polyps has a high risk of continuing on to become colon cancer.
There are several other terms you may hear if you’ve been diagnosed with an abnormal pap smear or had a biopsy of your cervix. These are described well in this article:
DiagnosisPrecancerous cells are diagnosed by their abnormal appearance under a microscope, usually after a biopsy is done.
CausesThere are many factors that can cause cells to become precancerous, and these vary depending upon the particular type of cells involved. A simplistic way of understanding causes is to look at influences in the environment that might damage healthy cells, leading to changes in the cell’s DNA, which can subsequently lead to abnormal growth and development. A few underlying processes that may cause abnormalities in cells (with a few examples to illustrate) include:
- Infection - While only 4 to 10% of cancers in the U.S. are related to infections, infections with viruses, bacteria, and parasites are responsible for roughly a fourth of cancers worldwide. Infection with the human papillomavirus (HPV) can cause inflammation, leading to precancerous cells in the cervix. HPV is also an important cause of dysplasia that precedes many head and neck cancers, such as tongue cancer and throat cancer. Most infections with HPV clear before any abnormal cell changes take place. If dysplasia develops, it may resolve on its own or with treatment, or progress to cervical cancer without treatment.
Infection and subsequent inflammation with the bacteria Helicobacter pylori (H. pylori) can result in chronic atrophic gastritis, an inflammatory precancerous change in the lining of the stomach that can lead to stomach cancer.
- Chronic Inflammation - Chronic inflammation in tissue can lead to precancerous changes that may in turn progress to cancer. An example is in people who suffer with gastroesophageal reflux disease (GERD) for a prolonged period of time. Chronic inflammation of the esophagus by stomach acids can result in a condition known as Barrett’s esophagus. Among people with Barrett’s esophagus, approximately 1% per year will develop esophageal cancer. An important area of research is determining whether or not removing areas of high-grade dysplasia will decrease the risk of developing esophageal cancer.
Another example is inflammation of the colon in people with inflammatory bowel disease (IBD). IBD can lead to polpys with colon dysplasia, which in turn can eventually lead to colon cancer.
- Chronic Irritation - Chronic irritation of the airways from tobacco smoke, air pollution, and some industrial chemicals can result in bronchial dysplasia (dysplasia of the bronchi). If this is detected early — during a bronchoscopy and a biopsy, for example — the precancerous cells may sometimes be treated with cryosurgery before they have the opportunity to progress to lung cancer.
Latency PeriodDiscussing precancerous changes is a good opportunity to talk about another difficult-to-understand concept in the development of cancer: latency. Latency is defined as the period of time between exposure to a cancer-causing substance (a carcinogen) and the later development of cancer. People are often surprised when they develop cancer many years after exposure to a carcinogen; for example, some people are perplexed when they develop lung cancer even when they'd quit smoking 3 decades earlier.
When cells are first exposed to a carcinogen, damage is done to the DNA in the cell. It's usually an accumulation of this damage (accumulation of mutations) over time that results in a cell becoming precancerous. Following that period, the cell may progress through stages of mild to moderate — and on to severe — dysplasia before finally becoming a cancer cell. The cell may also be exposed to an environment that inhibits its progression to cancer, or even reverts it to a normal cell (why a healthy diet and exercise are important even if you’ve been exposed to a carcinogen). This is a simplistic way of describing the process, and we are learning that it is much more complex than we once thought. But understanding the precancerous process does help explain the latency period we see with many cancers.
How Long Does it Take a Precancerous Cell to Become Cancerous?The answer is that, most of the time, we don’t know. In addition, the answer certainly varies depending on the type of cell studied. As noted above, cervical cells with severe dysplasia progressed to cancer 30 to 50% of the time, but the time frame that this took to happen was variable. In one study looking at 115 people with dysplasia of the vocal cords, 15 went on to develop invasive cancer (one had mild dysplasia, one had moderate dysplasia, 7 had severe dysplasia and 6 had carcinoma in situ). In 73% of these patients, their precancerous lesions became invasive cancer of the vocal cords within one year, with the remainder developing cancer years later.
SymptomsPrecancerous cells are often present without any symptoms. If symptoms are present, they will depend upon the location of the precancerous changes; for example, precancerous changes in the cervix may cause the cells to slough more easily, resulting in abnormal uterine bleeding. Precancerous changes in the mouth may be visualized as white spots (leukoplakia). And in regions that are not visible to the naked eye, such as the tissue lining the airways, dysplasia is most often detected when a screening biopsy is done for another reason.
How are Precancerous Cells Treated?The treatment of precancerous cells will again depend upon the location of the cells.
Sometimes close monitoring is all that is recommended to see if the level of dysplasia progresses or resolves without treatment.
Often the precancerous cells will be removed by a procedure such as cryotherapy (freezing the cells) or surgery to remove the region in which the abnormal cells are located. Even if the abnormal cells are removed, it’s important to keep in mind that whatever caused the cells to become abnormal in the first place may affect other cells in the future. For example, if abnormal cervical cells are treated with cryotherapy, it will still be important to monitor for recurrent problems with Pap smears in the future. And if Barrett’s esophagus is treated with cryotherapy, you will still need to have your esophagus monitored at intervals in the future.
For some abnormalities, your doctor may recommend chemoprevention. This is the use of a medication that reduces the risk of cells' becoming abnormal in the future. An example of this is treating an infection with the H. pylori bacteria in the stomach. Ridding the body of the bacteria appears to reduce precancerous cells, and also the development of stomach cancer. Researchers are looking at the use of several medications and vitamins to see if their use in former and current smokers will lower their risk of developing lung cancer in the future.
A last and important point to make is a reminder that, in some cases, the progression of precancerous changes may be altered by our environment: the foods we eat, the exercise we get, and the lifestyle choices we make. A diet rich in foods containing certain vitamins, for example, may help the body clear the HPV virus more rapidly.
Precancerous Progression Terminology
There are many terms describing cells that make understanding this topic difficult, so an example might help make this understanding a little clearer. With squamous cell lung cancer, it appears that cells go through a certain progression before cancer develops. It begins with normal lung cells; the first change is hyperplasia, which is defined as cells that grow larger or faster than expected. For example, hyperplasia of the heart would be the term used to describe an enlarged heart. The second step is metaplasia, when cells change to a type of cell not usually present. Metaplasia in the esophagus (which can be a precursor to esophageal cancer), for example, is when cells that look like those normally found in the small intestine are found in the esophagus. The third step is dysplasia, which is followed by carcinoma in situ and, finally, invasive squamous cell carcinoma.
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