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1. Essay on Cancer Screening: (Around 450 Words)
The Pap Smear Illustrates that Early Detection can Prevent Cancer Deaths:
Because cancers do not produce many symptoms in their early stages, there is an urgent need for better screening procedures that can detect the presence of cancer before any symptoms appear. The most successful screening technique thus far has been the Pap smear, a procedure for the early detection of cancer of the uterine cervix that was first introduced in the early 1930s by George Papanicolaou (for whom it is named).
The rationale underlying the Papanicolaou procedure is that the microscopic appearance of cancer cells is so distinctive compared to normal cells that it is possible to detect the likely presence of a malignancy by simply examining a few isolated cells under a microscope.
To obtain cells for examination, a doctor inserts a small brush and spatula into the vagina and uses them to scrape cells from the surface of the uterine cervix. The cells are then smeared across a glass slide—hence the name Pap “smear”—and the slide is stained and examined with a microscope.
If the cells in the specimen are found to exhibit abnormal features, such as numerous cells undergoing mitosis, cells with large irregular nuclei, and prominent variations in cell size and shape (Figure 2), it is a sign that cervical cancer may be present.
Abnormal cells detected in a Pap smear could also be a sign of infection or dysplasia rather than cancer. To make an accurate diagnosis, a doctor needs to cut out a small piece of tissue from the uterine cervix and have it examined under the microscope by a pathologist, who looks for the alterations in cell and tissue organization that are characteristic of cancer. This process of removing a piece of tissue for microscopic examination, called a biopsy, is the only way in which a definitive diagnosis of cancer can usually be made.
The enormous power of the Pap screening procedure is that it permits cervical cancer to be found before invasion and metastasis have occurred; it can even detect early dysplasia, thereby uncovering a potentially precancerous condition before it develops into cancer.
When the disease is caught in these early stages and treated appropriately, the survival rate is virtually 100%. Widespread use of the Pap smear has lowered the death rate from cervical cancer in the United States more than 75% since the procedure was first introduced in the 1930s, thereby preventing hundreds of thousands of cancer deaths.
Quite recently the usefulness of the Pap smear has been further improved by combining it with a DNA test for the human papillomavirus (HPV), which is linked to the development of cervical cancer.
2. Essay on Cancer Screening: (Around 400 Words)
Mammography is an Imaging Technique used in Screening for Early Stage Breast Cancers:
The enormous success of the Pap smear has stimulated interest in developing other screening procedures for early cancer detection. Screening for early breast cancer is performed using an X-ray procedure called mammography, which employs low-dose X-rays to create detailed pictures that reveal the internal tissues of the breast.
The main advantage of mammography is its ability to detect small tissue abnormalities that cannot be felt, although the procedure is not accurate enough to prove the presence or absence of cancer. If mammography reveals the presence of an abnormal tissue mass, a biopsy must be performed to determine whether it is actually a cancer.
Some disagreement has been voiced in the medical and scientific literature as to the exact age when women should begin mammography. At the time when this article was being written, the American Cancer Society and governmental agencies were recommending mammography every one to two years for women aged 40 and older.
Some scientists, however, have advocated caution in recommending mammography for women in their 40s because radiation itself can cause cancer. Although the level of radiation used in modern mammography is quite low, the younger a woman is when she begins annual mammography, the greater the lifetime dose of radiation she will eventually receive.
The benefits derived from starting mammography at a younger age therefore need to be balanced against the risks accumulated through radiation exposure. The only way to resolve this issue is through careful statistical analysis of the actual, real-life experiences of women who have used mammography.
Such analyses suggest that mammography is most beneficial for two groups of individuals:
(1) Women with an unusually high risk of developing breast cancer (mainly those with a mother or sister who have already developed the disease) and
(2) Women over 50, who are at higher risk of developing breast cancer because they are older.
The risk of dying of breast cancer for these older women appears to be reduced up to 30% through the routine use of mammography. The data suggest that younger women, in the 40 to 50 age group, may also derive some benefit from mammography, although the apparent reduction in mortality is much smaller than for older women and the statistics are not as compelling.
It is therefore possible that future recommendations concerning the exact age when women should begin routine mammography may change slightly as we acquire more experience and data concerning the use of this screening tool.
3. Essay on Cancer Screening: (Around 600 Words)
Colonoscopy, X-Ray Procedures, and the Fecal Occult Blood Test are used in Screening for Early Stage Colorectal Cancers:
Cancers of the colon and rectum cause more deaths in the United States than any type of cancer other than lung cancer, so there is a great need for effective screening procedures that can reduce the death rate through early detection. A variety of screening options are currently available, including direct visual examination of the colon and rectum, X-ray imaging, and biochemical testing of feces.
Procedures for direct examination of the colon and rectum utilize a slender, flexible, fiber-optic tube that is inserted into the anus, through the rectum (the last 6 to 9 inches of the large intestine), and into the colon, thereby allowing doctors to see the inner surface of the colon and rectum.
Colonoscopy uses a version of this instrument called a colonoscope, which is long enough to visualize the entire length of the colon (a shorter version is used for sigmoidoscopy, a similar procedure that allows only the left part of the colon to be seen). If any abnormal growths are found during colonoscopy, they can be biopsied or, in the case of small polyps, removed entirely with a tiny instrument that is inserted through the colonoscope.
X-ray imaging techniques are also employed in screening for colorectal cancer. In one procedure known as a barium enema, a physician administers liquid containing barium through the anus and into the rectum and colon. The barium compound helps improve the contrast of the image when X-ray pictures are taken.
However, the resulting X-ray images are still not as accurate as colonoscopy in detecting early cancers, and use of this technique has been dropping over the past decade. A newer X-ray procedure, called virtual colonoscopy, employs an X-ray scanner to take multiple pictures of the colon at various angles; the resulting data are then assembled by a computer to produce a three-dimensional reconstruction of the inner surface of the colon.
Virtual colonoscopy is not quite as sensitive as an actual colonoscopy for detecting the smallest polyps, but it is effective in detecting larger polyps and is currently being evaluated as a noninvasive alternative to conventional colonoscopy.
Another screening strategy involves biochemical testing of fecal samples for indications that cancer might be growing in the colon or rectum. Because colorectal cancers tend to bleed intermittently, one useful indicator is the presence of blood in the feces. A screening test called the fecal occult blood test (FOBT) is designed to detect such blood, even when it is present in amounts that are too small to be seen (hence the name “occult” which means “hidden”).
With an application stick, a dab of a stool specimen is simply smeared on a chemically treated card that is then tested in a laboratory for evidence of blood. If blood is detected, colonoscopy may be necessary to find the source of the bleeding. FOBT is not as sensitive or specific as colonoscopy, but it is less expensive, noninvasive, and more practical for routine testing, and its use has been shown to reduce death rates from colorectal cancer.
Other substances present in fecal samples might also indicate the presence of cancer. For example, colon cancer cells often have mutations in the APC gene. Since colorectal cancers continually shed cells from the inner surface of the colon or rectum, small amounts of DNA from these cells end up in the feces. Researchers have shown that techniques capable of detecting tiny amounts of DNA can identify the presence of DNA containing APC mutations in fecal samples obtained from individuals with colorectal cancer.
Although the procedure is not yet in routine clinical use, such approaches are currently being evaluated, and it is possible that screening stool samples for DNA mutations may improve our ability to detect early colorectal cancer in the not-too-distant future.
4. Essay on Cancer Screening: (Around 650 Words)
Blood Tests for Cancer Screening include the PSA Test for Prostate Cancer as well as Experimental New Proteomic Techniques:
The ideal screening test would allow doctors to detect early stage cancers anywhere in the body with one simple procedure, such as a blood test. Prostate cancer is an example of a cancer that can sometimes be detected in this way. Men over the age of 50 are advised by many doctors to get a PSA test, which measures how much prostate-specific antigen (PSA) is present in the bloodstream.
PSA is a protein produced by the prostate gland that normally appears in only tiny concentrations in the blood. If a PSA blood test reveals a high concentration of PSA, it indicates the existence of a prostate problem that might be an infection, hyperplasia, or cancer.
A biopsy therefore needs to be performed to determine whether cancer is actually present. If cancer is diagnosed, blood tests for PSA may be used again later to determine how many cancer cells remain after treatments are administered to remove or destroy the cancer.
A number of other cancers also produce proteins that are released into the bloodstream in elevated amounts. Two of these proteins were: alpha-fetoprotein, which is produced by some liver cancers, and carcino embryonic antigen (CEA), which is produced by some colon, stomach, pancreatic, and lung cancers.
Another example is CA125, a protein released into the bloodstream by many ovarian cancers. The presence of such proteins in the blood is not reliable enough to be used for routine cancer screening, but they are measured in some cancer patients to monitor the course of a person’s disease and its responsiveness to treatment.
Researchers are currently trying to identify other proteins in the blood that might be better indicators of the presence of specific cancers. One technique being applied to the problem is known as proteomic analysis (the term proteome refers to all the proteins produced by a cell or organism).
The key to proteomic analysis is mass spectrometry, a high-speed, extremely sensitive method for identifying proteins based on differences in mass and electrical charge. Mass spectrometry permits rapid examination of the protein makeup of a tiny sample, such as a drop of blood, creating a snapshot of thousands of proteins at once (Figure 3).
To overcome the difficulty in trying to look at patterns involving thousands of proteins to see which ones might indicate the presence of cancer, computer scientists have developed software programs to tackle the job. These computer programs can compare the complex proteomic patterns seen in blood samples from individuals with or without cancer and identify small changes that are associated with certain kinds of cancer.
One of the first cancers to be investigated in this way was ovarian cancer. When ovarian cancer is detected before it spreads beyond the ovaries, the five-year survival rate is better than 95%. Early disease has few symptoms, however, and relatively few cases are detected early, so less than 50% of women with the disease end up surviving more than five years.
Hence better detection techniques are urgently needed. Using proteomic analysis, scientists have uncovered a diagnostic proteomic pattern in the blood of women with ovarian cancer that does not appear in the blood of other women. Initial studies indicated that the test had a specificity of about 95%, which means that 95 out of 100 women exhibiting the abnormal pattern of blood proteins will have ovarian cancer.
Subsequent reports suggest that it may be possible to improve the sensitivity even further, and a commercial version of such a test is under development. Questions have been raised, however, concerning the reliability of this approach, and the validity of the test needs to be independently confirmed.
The development of proteomic screening is thus still in its infancy, and much work remains to be done before we will know whether cancers can be reliably detected in their early stages using proteomic analysis to identify small changes in blood protein composition.
5. Essay on Cancer Screening: (Around 700 Words)
False Negatives, False Positives, and Over Diagnosis are Some of the Problems Encountered with Cancer Screening Tests:
Screening tests are intended to reduce cancer deaths through early detection, but two criteria must be met before we can be confident that a given test is actually accomplishing this objective. First, effective methods must be available for treating any cancers that are detected through early screening. Second, screening tests must exhibit sufficient sensitivity and specificity to minimize the potential problems that would be created by incorrect test results.
The sensitivity of a cancer screening test addresses the question- What percentage of the people with a given type of cancer will have their cancer detected when a screening test is used? If a test is not very sensitive, there will be many false negative results in which a person who has cancer obtains a negative test result—that is, the cancer is not detected.
A test that yields many false negatives will not be very effective at reducing cancer deaths and may even be counterproductive, giving a false sense of security to people who do have cancer.
In contrast, the specificity of a screening test addresses the question- What percentage of the people who do not have cancer are correctly identified as being free of the disease? If a screening test is not very specific, it will yield many false positive results; that is, people will test positive even though they do not have cancer.
A false positive can lead to unnecessary and costly follow-up procedures as well as anxiety to the person involved. Moreover, the number of false positives can easily exceed the number of correct positives if the overall cancer rate is relatively low in the population being screened, which is the case for many cancers (Figure 4).
To illustrate the relevance of these concepts to a real- life situation, let us briefly consider the FOBT screening test for the early detection of colorectal cancer. The FOBT test has a reported specificity as high as 98% (2% false positives), which at first impression sounds like a high level of specificity.
However, the annual incidence of colorectal cancer in the United States for the overall population is currently about 55 cases per 100,000. So, if 100,000 people were randomly tested once per year using the FOBT test, the result would be 2% x 100,000 = 2000 false positives in a population that has only 55 new cases of colorectal cancer.
Thus a 2% false positive rate yields so many incorrect results relative to the number of real cancer cases as to make the procedure almost useless for random testing. On the other hand, colorectal cancer rates increase dramatically as people get older, rising roughly tenfold between 30 and 50 years of age and another fivefold between 50 and 70 years of age. If FOBT testing is restricted to older populations, the ratio of real cancer cases to false positives increases dramatically and the test becomes more useful.
It may seem counterintuitive, but another problem that can arise with cancer screening techniques is the detection of cancers that would not otherwise have been a health hazard. This situation, known as over diagnosis, has been documented for prostate cancer, a common disease in older men that often arises in slow-growing or dormant forms.
Current research suggests that at least 30% of the men whose prostate cancers are detected through PSA screening have tumors that would not otherwise have been detected or created any health problems during their lifetime. Diagnosing cancer in such individuals is likely to cause anxiety and lead to unneeded treatments with potentially adverse side effects.
On the other hand, men who avoid the PSA test to avert the possibility of over diagnosis face the risk of missing the detection of an aggressive prostate cancer whose early detection could have saved their lives. What we clearly need is better screening tests that can distinguish between aggressive cancers that is potentially life threatening and those cancers that are not serious and would be better left alone.
6. Essay on Cancer Screening: (Around 600 Words)
A Biopsy can Diagnose the Presence of Cancer before Invasion and Metastasis have begun:
When the results of a cancer screening test are “positive” (i.e., abnormal), it does not mean that a person necessarily has cancer, but it does indicate the need for follow-up evaluation to determine the exact nature of the underlying problem. A definitive diagnosis generally requires that a biopsy specimen be taken from the suspected tumor site and examined with a microscope, looking for the changes in cell structure, mitotic rate, and tissue organization that signal the presence of malignancy.
Although a biopsy is always desirable, it may be difficult to obtain the required tissue specimen when the tumor is located in a relatively inaccessible site, such as the brain or in an organ deep within the body.
For example, headaches and other neurological symptoms occasionally indicate the presence of a brain tumor, but a brain biopsy would not be attempted to obtain an initial diagnosis. In situations in which performing a biopsy would be difficult, or when the precise location of a possible tumor needs to be determined before it can be biopsied, diagnostic imaging techniques are used to take pictures of the inside of the body.
Imaging techniques utilize X-rays, magnetic fields, or ultrasound to form images. In the case of X-ray imaging, a variety of approaches are available. Conventional X-ray procedures (for example, a chest X-ray) may be useful for the initial identification of tissue abnormalities. In some organs, administering an electron opaque liquid containing barium can help increase the contrast of the X-ray pictures.
The highest resolution images are produced by a computed tomography scan (CT scan), a technique in which an X-ray scanner moves around the body taking multiple pictures that are then assembled by a computer into a series of detailed cross-sectional images. Magnetic resonance imaging (MRI) involves a similar approach using strong magnets and radio waves instead of X-rays, thereby generating a more accurate image.
Ultrasound imaging uses sound waves and their echoes to produce a picture of internal body structures. High-frequency sound waves are transmitted into the region of the body being studied, the echoes are picked up by a receiving instrument, and a computer converts the data into a visible image.
If one or more imaging techniques reveals an abnormal tissue mass within the body, a biopsy is usually performed. Microscopic examination of a biopsy specimen permits a definitive diagnosis of cancer to be made, even if the tumor has not yet invaded or metastasized.
In other words, even though cancer is defined as a growth that can spread by invasion and metastasis, microscopic examination permits a tumor harboring this potential to be identified before it has actually invaded surrounding tissues or metastasized to other areas of the body. In essence, doctors are able to see into the future, predicting that a tumor will invade and metastasize at some future time even though it has not yet done so.
A cancer that has been diagnosed before invasion has taken place is said to be in situ (“in place”). This term is most commonly applied to cancers of epithelial origin—that is, carcinomas—because epithelial cell layers are separated from underlying tissues by a distinct boundary structure that makes it relatively easy to determine whether a cancer has begun to spread.
This boundary structure, called the basal lamina, is a thin, dense layer of protein-containing material that forms a barrier between an epithelial cell layer and the underlying tissue (Figure 5). A cancer that has not yet invaded through the basal lamina is called a carcinoma in situ, meaning that it is still in its preinvasive stage.
