|
Untitled Document
|
 |
|
|
|
|
|
Oral Cancer
| Oral cancer is the sixth most common cancer, accounting for 40,000 newly diagnosed cancers each year and 9,000 deaths. Less than half of all oral cancer patients are cured, because the disease usually is diagnosed in its later stages. You are more likely to develop oral cancer if you are a male over the age of 45.
While the potential for oral cancer may be genetically inherited, the risk increases for smokers, spit tobacco users, too much exposure to sunlight and excessive alcohol consumption. Habits such as lip or cheek biting and ill-fitting dentures also heighten the risk of developing oral cancer.
The most prevalent oral cancer sites are the tongue, floor of the mouth and the soft palate. But oral cancer may also be found on the lips, cheeks or gums.
Many dental offices perform a free oral cancer examination during routine check-ups. Looking for certain indicators and palpating (feeling) for lumps or irregular tissue changes in your mouth, head and neck. A biopsy will be conducted on any suspected areas. Treatment for oral cancer is surgical removal of the lesion and is sometimes followed by radiation therapy.
In addition to regular check-ups, you can perform self-examination to look for early warning signs. Basically, look for anything out of the ordinary, especially a lump that increases in size; a sore that doesn't heal within two weeks; and/or changes in the appearance of soft tissue. Other early warning signs are persistent bleeding from the throat or mouth, difficulty swallowing, constant hoarseness, and numbness anywhere in the mouth. To perform your own oral cancer examination, start in one area and consistently follow a pattern of observation and palpation.
Face and neck - using a mirror and your nose as the dividing line, look for lumps or swellings that appear on only one side. Look for size or color changes in moles or other growths. With your fingers, press the sides and front of your neck, feeling for lumps or tenderness.
Lips - Pull your lip down or up to observe any sores or color changes. Run your lip between your thumb and forefinger, feeling for lumps or changes in texture.
Cheeks, roof of the mouth, floor of the mouth, tongue, and gums - Look for red, white or dark patches or open sores. Feel for lumps and bumps.
Oral cancer is painless in the early stages. With early discovery and treatment, survival rates greatly increase. If you detect any of these early warning signs, call or see your dentist immediately.
------------------------------------------------------------------------------------------------------------------------------------------------------------------
Detecting Oral Cancer - (for for Health Care Professionals)
Oral or pharyngeal cancer will be diagnosed in an estimated 28,000 Americans this year, and will cause approximately 7,000 deaths. On average, only 59 percent of those with the disease will survive more than five years.
The Importance of Early Detection
Early Detection Saves Lives
With early detection and timely treatment, deaths from oral cancer could be dramatically reduced.
The five-year survival rate for those with localized disease at diagnosis is 81 percent compared with only 30 percent for those whose cancer has spread to other parts of the body.
Early detection of oral cancer is often possible. Tissue changes in the mouth that might signal the beginnings of cancer often can be seen and felt easily.
Warning Signs
Lesions that might signal oral cancer
Two lesions that could be precursors to cancer are leukoplakia (white lesions) and erythroplakia (red lesions). Although less common than leukoplakia, erythroplakia and lesions with erythroplakic components have a much greater potential for becoming cancerous. Any white or red lesion that does not resolve itself in two weeks should be reevaluated and considered for biopsy to obtain a definitive diagnosis.
Other Possible Signs and Symptoms:
Possible signs and symptoms of oral cancer that your patients may report include: a lump or thickening in the oral soft tissues, soreness or a feeling that something is caught in the throat, difficulty chewing or swallowing, ear pain, difficulty moving the jaw or tongue, hoarseness, numbness of the tongue or other areas of the mouth, or swelling of the jaw that causes dentures to fit poorly or become uncomfortable.
If these problems persist for more than two weeks, a thorough clinical examination and laboratory tests, as necessary, should be performed to obtain a definitive diagnosis. If a diagnosis cannot be obtained, referral to the appropriate specialist is indicated.
Risk Factors
Tobacco/Alcohol Use
Tobacco and excessive alcohol use increases the risk of oral cancer. Using both tobacco and alcohol poses a much greater risk than using either substance alone.
Sunlight
Exposure to sunlight is a risk factor for lip cancer.
Age
Oral cancer is typically a disease of older people, usually because of their longer exposure to risk factors. Incidence of oral cancer rises steadily with age, reaching a peak in persons aged 65-74. For African Americans, incidence peaks about 10 years earlier.
Gender
Oral cancer strikes men twice as often as it does women.
What You Can Do
A thorough head and neck examination should be a routine part of each patient's dental visit and general medical examination. Clinicians should be particularly vigilant in checking those who use tobacco or excessive amounts of alcohol.
- Examine your patients using the head and neck exam illustrated in this program.
- Take a history of their alcohol and tobacco use.
- Inform your patients of the association between tobacco use, alcohol use, and oral cancer.
- Follow-up to make sure a definitive diagnosis is obtained on any possible signs or symptoms
Confronting the Enemy
Oral or pharyngeal cancer will be diagnosed in an estimated 30,000 Americans this year, and will cause more than 8,000 deaths. The disease kills one person every hour -- more people than cervical cancer, Hodgkin's disease, or malignant melanoma. When the definition of oral cancer is expanded to include laryngeal cancer, which shares risk factors with oral cancer, the number of cases in the United States, per year, climbs to 41,000 and the number of deaths to 12,500. Oral cancer is the sixth most common cancer worldwide and the third most common in developing nations.
Some might say the old adage, "the cure is worse than the disease," applies to existing treatments for oral and pharyngeal cancers. Victims of oral cancer not only deal with the debilitating side-effects of radiation and chemotherapy but with the very visible evidence of surgery. Surgery to treat oral cancer is often extensive and disfiguring and may involve removing parts of the face, tongue, cheek, or lip -- causing changes in appearance that can be especially difficult to live with in a society that values physical beauty. Chemotherapy and radiation to the head and neck cause their own problems: jaw pain, mouth sores, and salivary glands that cease to function, resulting in difficulty chewing, swallowing, and talking. Recovering the ability to speak clearly and adjusting to new oral prostheses are additional challenges.
As with any cancer, the threat of death is an overriding fear. Most disturbing about oral and pharyngeal cancer is the survival rate. In the United States it is approximately 50 percent, a statistic that has not changed appreciably over the past 20 years. Oral cancer is unusual in that it carries a high risk of second primary tumors. Patients who survive a first cancer of the oral cavity have up to a 20-fold increased risk of developing a second primary oral cancer. The heightened risk can last 5-10 years, sometimes longer. Until researchers learn more about this phenomenon, second primary tumors will remain a specter faced by all oral cancer patients.
Additionally, oral cancer, like many diseases, continues to take a disproportionate toll on minorities. Incidence peaks in African Americans 10 years earlier than in the general population, in whom the disease is usually diagnosed between ages 65-74. The difference in survival rates between whites and African Americans is staggering -- 55 percent of whites survive five or more years, while only 34 percent of African Americans live that long. African American males suffer the highest incidence and lowest survival rates of any group. Oral cancer is the fourth most common cancer among African American men in the United States.
How Cancer Develops
We've known for a long time that cancer cells, unlike normal cells, multiply uncontrollably, ignoring the usual signals to stop. We also know that cancer cells can metastasize -- migrate from their original site and set up shop in another part of the body, where they continue to multiply unchecked.
But over the past two decades cancer research has uncovered much more. We now know that all neoplastic transformations (cancers) result from mutations, or changes, in genes that control cell growth and behavior. These genes normally restrict cell proliferation and direct the cell to repair DNA damage, or failing that, to self-destruct, a process called apoptosis, or cell 'suicide.' The mutated genes free the cell from these controls, allowing it to divide continuously and to pass on the mutation(s) to its progeny.
What causes these mutations? Many factors come together to cause each type of cancer. Genetic mistakes can be inherited or they can be acquired as a result of exposure to chemicals, radiation, or viruses. Random mistakes also occur each day in the course of duplicating the three billion units in our DNA during cell division. No one mutation is enough to make a cell cancerous. Multiple genetic changes, in specific classes of genes, are needed to transform a normal cell into a neoplastic cell that grows out of control. A small percentage of people inherit a susceptibility for certain types of cancer, putting all their body's cells one step closer to the disease.
Oral Cancer
Scientists now understand that oral cancers, which are included in the category of head and neck cancers, result from a multistep process of accumulated genetic mutations caused by many factors. Tobacco and alcohol use, diet, viruses, and a possible genetic susceptibility may all work together in various combinations to cause these cancers.
Using tobacco -- including cigarettes, pipes, cigars, and spit tobacco-is a well-established risk factor for oral cancer, as it is for some other cancers. Tobacco in any form contains carcinogens and nicotine, an addictive chemical that can keep the user hooked. A popular betel quid-spit tobacco mixture, used throughout India, has been implicated in the high rate of oral cancer in that part of the world.
Excessive alcohol consumption can also increase a person's chance of developing oral cancer. One theory suggests that alcohol generates metabolites, or byproducts of metabolism, that are carcinogenic to humans; the major metabolite of ethanol is acetaldehyde, a recognized animal carcinogen. Alcohol also might "grease the wheels" for tobacco by acting as a solvent and making it easier for carcinogenic agents to penetrate the oral tissues.
Using both tobacco and alcohol produces a much greater risk for oral cancer than using either substance alone. It is estimated that approximately 75 percent of all oral and pharyngeal cancers in the United States are caused by smoking and drinking, with most of these cases caused by tobacco and alcohol working synergistically.
Viruses, too, are thought to be involved in the development of these cancers. The human papillomavirus (HPV), particularly the HPV-16 and HPV-18 strains, and the herpes viruses are now considered possible contributors to some cases of oral cancer. DNA from HPV and certain herpes viruses, including Epstein-Barr, cytomegalovirus, and herpes simplex, has been detected in oral cancer biopsies. Genes encoded within these viruses are implicated in the initiation of the multiple steps required for a normal cell to become malignant. Interestingly, scientists have recently linked a new virus with AIDS-related Kaposi's sarcoma (KS), a cancer that has a preference for the head and neck. Oral lesions are present in about half of KS cases and the hard palate and gingiva are the most commonly affected areas. The newly identified virus, called human herpesvirus 8, has been found in all forms of KS, suggesting it might be involved in the sarcoma's development. A direct causal role, however, has not yet been established.
Research also suggests that a diet lacking fruits and vegetables could contribute to oral cancer, an idea postulated about other cancers as well. These foods contain antioxidants that trap harmful molecules, a process that can help prevent cancer-causing genetic mutations. The consumption of Cantonese salted fish from early childhood on has been associated with oral cancer in some Asian countries.
Virtually all oral cancers are squamous cell carcinomas, cancers of the epithelial cells that line many parts of the body, including the mouth. These cancers can develop in any part of the oral cavity or oropharynx. The most common sites are the tongue, the lips, and the floor of the mouth. Cancers of the hard palate are uncommon in the United States. Research has shown that changes in oral epithelial cells often are manifested as lesions called leukoplakia, a white patch, or erthyroplakia, a red patch, which can be early signs of oral cancer.
Research is revealing what goes on beneath the cell surface -- at the genetic level -- to set the cancer process in motion. Scientists now realize that multiple mutations in specific classes of genes contribute to head and neck cancer. The two classes most fully characterized to date are proto-oncogenes and tumor suppressor genes. Proto-oncogenes code for proteins that stimulate cell division; altered forms, called oncogenes, can cause stimulatory proteins to be overactive, with the result that the cell divides more rapidly than usual. Scientists have so far identified the oncogenes (EGFR)/c-erb 1, ras family, c-myc, int-2, hst-1, PRAD-1 (CCND1 or cyclin D1), and bcl-1 as possible participants in head and neck cancers.
Tumor suppressor genes code for proteins that inhibit cell division. When these genes mutate, the corresponding protein may no longer be produced correctly and cell division may occur when it should not. Inactivated tumor suppressor genes that are suspected in head and neck cancer include Rb, p16 (MTS1 or CDKN2), and p53, whose failure is already implicated in approximately 60 percent of all human cancers. p53 has been of great interest to cancer researchers since it was discovered that the molecule could stop tumors from forming when it is functioning properly. Located on the short arm of chromosome 17, p53 works by recognizing damage to a cell's DNA and stopping the process of cell growth and division until the damage is repaired. If that fails, p53 can launch the cell's 'suicide' software, causing the cell to undergo apoptosis.
As more and more genetic events are implicated in head and neck cancers, scientists are now converging on the next question: in what order do those events occur to cause tumor development? One team has already proposed part of the answer by developing a preliminary genetic progression model for head and neck cancers.
The National Institute of Dental and Craniofacial Research
Knowing the order and manner of genetic events involved in head and neck cancers has obvious appeal. Health professionals and patients can now look forward to confronting cancer on the molecular level -- where it originates -- instead of waiting to deal with its aftermath. It may one day be possible to detect the disease at its earliest stage using biomarkers found in blood and saliva; develop better tests for tracking the progression of cancer; and design therapies based on fixing or replacing mutated genes.
Through its grants program -- including the Oral Cancer Research Centers co-funded with the National Cancer Institute -- and in projects conducted on the NIH campus, NIDCR is seizing the opportunity to explore the range of topics related to oral and pharyngeal cancer. This article describes only a few of NIDCR's ongoing efforts and a handful of findings by NIDCR researchers and others in this burgeoning field.
Viruses, Variations, and Environment-Studies on Oral Cancer Etiology
For many years the human papillomavirus (HPV) has been suspected as a possible culprit in the etiology of oral cancer. Two types of the virus, HPV-16 and HPV-18, are found in oral cancer tissues more frequently than in normal tissues. Scientists are still not sure, though, how HPV might contribute to the development of oral cancer.
Recently, a team of NIDCR-funded investigators at the State University of New York Health Sciences Center in Syracuse discovered mutations in the long control region (LCR) of HPV-16 and HPV-18 taken from oral cancer cell lines. This region of the virus plays an important role in regulating the expression of two viral genes called E6 and E7. Earlier research implicated overexpression of these two genes in the development of cervical cancer, and the oral cancer researchers suspect the same phenomenon might be at play producing oral neoplasms. They speculate that the LCR mutations disturb the normal balance between up- and down-regulation of E6 and E7, leading to their overexpression and thus to oral cancer. Future research by these scientists and others will focus on trying to locate concrete molecular evidence of E6 and E7 overexpression in oral cancer cells. Taken together, these studies will eventually help confirm, or rule against, HPV's involvement in oral cancer development.
Animal and cell line studies have led two other groups of NIDCR grantees to make discoveries about genetic variations that might play a part in oral cancer development. At the Harvard School of Dental Medicine one group has identified, isolated, and partially characterized an oral tumor suppressor gene. Discovered in the hamster oral cancer model, the gene is dubbed 'doc-1' for 'deleted in oral cancer.' The mutation of this gene in malignant hamster oral keratinocytes leads to a reduction of its expression and protein production, while re-expression of the gene results in the reversion of malignant phenotypes to normal.
Importantly, the scientists now have data to support the existence of a human version of doc-1. They also have evidence that the gene seems to work by regulating cell cycle progression, as do other tumor suppressor genes such as Rb and p53. Studies are currently under way to determine whether doc-1 is a tissue-specific tumor suppressor or whether it might be involved in the development of other cancers as well.
A team of NIDCR-supported scientists at the University of Pittsburgh has shown that genetic variations occurring in head and neck cancers have been extended to include the FHIT gene, which was not previously associated with these malignancies. The finding that 22 of 26 squamous cell carcinoma lines showed aberrations in this gene strongly indicates that its function may be important in the development and progression of these neoplasias. Studies on the FHIT gene are continuing, and the scientists hope their findings will add to the knowledge of underlying genetic variations related to oral cancer.
A country halfway around the world and a U.S. island territory are the sites of two NIDCR studies correlating environmental and biological factors with oral cancer. In Taiwan, researchers are studying families with multiple members affected by nasopharyngeal cancer (NPC). The study capitalizes on recent investigations of NPC in Taiwan that found strong evidence of a genetic susceptibility to the disease and identified dietary factors that might contribute to its development. The current project is providing scientists with an ideal opportunity to investigate the association of NPC with environmental factors such as diet and to identify and characterize susceptibility genes for the disease. The molecular genetic work resulting from this study will almost certainly have implications for research into other subtypes of oral and pharyngeal cancer.
Closer to home, a case-control study of oral cancer is continuing in Puerto Rico, chosen as a study site because of its high oral cancer mortality rate for males. One of the study's strengths is that it is population-based, with cases derived from the island's central cancer registry. Biological specimens and information on diet and the use of tobacco and alcohol have already been collected from the 800-plus participants, and data analysis has begun. The idea is to discover how behavioral factors and genetic variations influence the development of oral cancer.
Diagnosing the Disease
Currently, diagnosing oral cancer relies on studying the histopathology of tissues through biopsy. X-ray technologies, like computed tomography, and other imaging techniques such as magnetic resonance imaging are sometimes used to detect the location and extent of the primary tumor. These techniques can help determine the stage of the tumor based on its size and whether it has spread. But cancer that can be evaluated by these imaging technologies has already taken root. Now, scientists are looking for ways to find cancer before it becomes clinically evident. To this end, many investigators are searching for markers at the molecular level that could warn of impending cancer.
In one such search for biomarkers, scientists at the University of Texas M.D. Anderson Cancer Center, an NIDCR Oral Cancer Research Center, are looking for alterations in short sequences of DNA called "microsatellites" on p53 and five other genes that might signal oral cancer. By examining cell samples from archived tissue of normal and dysplastic epithelium and invasive lesions, they plan to determine the most consistent biomarkers for each stage of oral cancer. In another phase of the study, the researchers will use tissue from recently diagnosed oral cancer patients to correlate genetic biomarkers with disease stage, tissue changes, tumor aggressiveness, and key epidemiological factors over several years.
One molecule already suspected as a predictor of head and neck cancers is telomerase. This enzyme helps a cell to reproduce chromosomal ends and circumvent the mechanism that counts and limits the total number of times the cell can reproduce. When cells become immortal they appear to bypass this safeguard and are able to replicate without limit. Telomerase is absent from most healthy cells, but present in almost all tumor cells. Scientists at Johns Hopkins University in Baltimore have recently found evidence of telomerase activity in oral rinses collected from head and neck cancer patients. Further research is necessary to discover whether telomerase is a marker consistently associated with head and neck squamous carcinoma. If so, telomerase activity may one day be used to detect the presence of cancer cells in the oral cavity and upper aerodigestive tract.
Until reliable biomolecular markers are identified, clinicians must rely on visual examination of oral tissues to detect precancerous lesions. Research by NIDCR, however, has indicated that less than 15 percent of American adults report they have ever had the head and neck examination that could reveal early signs of cancer. In an effort to improve this situation, NIDCR is focusing on encouraging dentists and other health care practitioners to perform this simple, potentially lifesaving, screening examination.
NIDCR's National Oral Health Information Clearinghouse (NOHIC) distributes a poster titled, "Detecting Oral Cancer: A Guide for Health Care Professionals," which offers a step-by-step pictorial guide on how to conduct the exam. Additionally, NOHIC has developed a companion slide show based on the poster. The slide show is distributed with a script and copies of the poster, patient education pamphlet titled, "What You Need to Know About Oral Cancer," and 'tips card' that lists signs and symptoms of the disease. NOHIC sends these materials to dentists, physicians, nurse practitioners, and other health care providers around the country.
Degrading and Invading-Studying Metastasis
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream or lymph system. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissue. By degrading these proteins, cancer cells are able to breach the ECM and escape. When oral cancers metastasize, they commonly travel through the lymph system to the lymph nodes in the neck.
In studying oral cancer metastasis, scientists at the NIDCR-NCI Oral Cancer Research Center at the University of Alabama at Birmingham are focusing on matrix metalloproteinases (MMPs), a group of enzymes implicated in the metastatic process. Currently, they are looking at the MMP collagenase, an enzyme that can degrade collagen -- one of the ECM proteins. In healthy tissue, collagenase is activated only at appropriate times, and reacts with collagen to aid in wound healing, in fighting infection, and in the normal turnover of cells. In cancer, however, collagenase becomes active at the wrong time and enables cells to escape from the parent tumor.
Early data from the collagenase studies suggest that many oral tumor cells can produce the active form of the enzyme. In one of their experiments, the scientists used purified collagen in a tissue culture dish as an extracellular matrix model and then placed human oral tumor cells on top of the collagen. Upon removing the tumor cells, the scientists found a hole eaten through the collagen layer -- evidence, they say, that activated collagenase was present underneath the tumor cells. The researchers ultimately hope to prevent collagenase activation in tumor cells and pre-empt the metastatic process.
At the University of California, San Francisco, another NIDCR-NCI Oral Cancer Research Center, researchers are studying a viscous molecule called hyaluronic acid (HA), a building block of the "glue" that anchors cells to one another. The molecule is present on the surface of cancer cells as well, and allows them to become motile and to create space into which they can move, two requirements for metastasis. Saliva's HA-rich environment gives cancer cells further opportunity to fulfill these two requirements, and may be the reason oral cancers can be so aggressive, the scientists say. In some cancers, high levels of HA and its receptor, CD44 (in certain forms), have been correlated with advanced metastatic behavior. In these latest NIDCR studies, the scientists will evaluate whether HA and CD44 are predictors of oral cancer metastasis by documenting their levels in cell culture and in human biopsy specimens. The scientists say these potential biomarkers may be of enormous value in identifying patients at increased risk for developing malignancy, and also in predicting which lesions might be particularly aggressive. Additional studies are aimed at trying to determine whether hyaluronidase, an enzyme that breaks down HA, can inhibit oral cancer metastasis.
One compound that has already shown anti-metastatic activity is a non-antimicrobial tetracycline analogue called CMT-3. Current research on this molecule evolved from earlier NIDCR studies on periodontal disease that found tetracyclines could inhibit collagenase activity independently of their antibiotic property. In recent laboratory tests, NIDCR-funded researchers at the State University of New York at Stony Brook found that CMT-3 inhibits cancer cells from degrading and crossing synthetic basement membrane. The analogue also showed promise in a rat model of prostate cancer in which it reduced tumor size in some animals, caused tumor remission in others, and inhibited metastasis to the lung. Additional safety and efficacy studies, now under way, are necessary steps in moving toward the planned clinical testing of this compound. Further anti-metastasis studies could lead to application of CMT-3 in treating many cancers, including oral cancer.
Curbing a Killer
Traditionally, surgery and radiation were the only treatments thought to be effective against oral cancer, with chemotherapy used as a palliative measure. Within the last decade scientists have found that certain drugs do indeed work against oral cancer. Researchers are now using radiation and chemotherapy in tandem, giving cancer a 'one-two' punch in an effort to knock it out. One of the newest drugs in the oral cancer treatment armamentarium is paclitaxel (Taxol, Bristol-Myers Squibb Co.), which has shown some success in treating other cancers. Currently, clinical researchers are studying paclitaxel as a treatment for oral cancer, using the drug by itself and in combination with other chemotherapeutic agents and radiation therapy.
Long before drugs are used in the clinic, they undergo extensive testing for safety and efficacy. Countless compounds initially thought to have some activity against cancer ultimately fail. But a few, like paclitaxel, do not. So researchers continue to screen thousands of compounds searching for those that show evidence of antitumor activity. Recently, NIDCR and the National Cancer Institute have become partners in the effort to identify natural or synthetic agents that demonstrate activity against squamous cell carcinoma. NIDCR is now testing the ability of certain agents -- already shown to have antitumor activity by an NCI cell line assay -- to diminish growth of squamous cell carcinoma lines in vitro and in vivo . The scientists hope to confirm the efficacy of these compounds and move them a step closer to clinical testing.
Other research is focused on inventing new systems to test potentially therapeutic compounds. NIDCR-funded investigators at the M.D. Anderson Cancer Center are developing a unique tissue slice organ culture (TSOC) that consists of normal, premalignant, and malignant human oral tissue slices kept alive in the laboratory. The advantage of the TSOC is that it preserves tissue organization, cell interaction, and cell function more so than do cultured cell lines. Because the model essentially mimics in vivo conditions, it is ideal for testing numerous agents in various amounts and combinations. Oral cancer research has been hindered by the methods usually employed to investigate growth and differentiation of normal and premalignant oral cells. Culturing normal oral cells is complicated, and no successful method for culturing genuine premalignant oral cells exists. The scientists hope to establish the TSOC system as the standard for examining normal, premalignant, and malignant oral tissues.
Using the TSOC the scientists are looking at the ability of vitamin A analogues (retinoids) and sodium butyrate, a four-carbon fatty acid, alone or in combination, to reverse aberrations in cell growth and differentiation. Scientists already know that one retinoid, called isotretinoin, can reverse premalignant oral lesions; however, the analogue has side effects that preclude its prolonged use. One of the research goals is to identify other retinoids with similar or better efficacy than isotretinoin, and analyze them to determine whether they may have fewer side effects. If so, these compounds could be candidates for clinical testing. The scientists also hope to investigate whether butyrate might be effective in preventing or treating oral malignancies.
Complementing the vast array of laboratory experiments are clinical studies aimed at testing new cancer treatments or helping to improve the quality of life for patients living with the disease. At the University of Chicago and Northwestern University, another NIDCR-NCI Oral Cancer Research Center, scientists in one clinical study are looking at the chemotherapeutic effects of 5-fluorouracil (5-FU) in combination with radiation therapy. One problem with using this drug has been that the enzyme dihydropyrimidine dehydrogenase (DPD) can degrade 5-FU and lower its level in the body below a therapeutic range. To circumvent this problem, the scientists are testing 5-FU in combination with a chemical that blocks DPD action, which might keep the cancer-fighting drug at its therapeutic level. Scientists will correlate the activity of 5-FU with enzyme activity and with patient response and survival. By conducting studies aimed at elucidating the idiosyncrasies of this powerful drug, the researchers hope to learn how to use it most effectively against oral cancer.
In patients with advanced cancer, one of the primary goals is to reduce the symptoms of large tumors and preserve organ function, thus maintaining or improving quality of life. This is the focus of another study at the University of Chicago-Northwestern University. Clinicians are analyzing the effects of high-dose radiotherapy combined with chemotherapies on tongue strength and swallowing function in patients with advanced cancer. Using the latest imaging techniques, scientists are able to observe even minute changes in organ function.
Biotherapies
Suppose there were a mutant cold virus that killed only cancer cells? Or a genetic 'cocktail' whose ingredients could provoke tumor-specific immune activity? Or what if there were a technique that allowed clinicians to replace a damaged p53 gene with a normal version? In fact, these are all therapies under study by head and neck cancer researchers right now. They are examples of a new approach to cancer treatment known as 'biotherapy.' Biotherapies are biological, based on the molecules and genes involved in the cancer process. A decided advantage of these therapies is that unlike chemically based chemotherapy or physically based radiotherapy -- which can harm healthy cells as well as tumor cells -- biotherapies can target tumor cells but leave other cells relatively unscathed. How successful will these therapies turn out to be? Ongoing research, like that described below, will eventually be able to give us the answer.
One biotherapy being studied at ONYX Pharmaceuticals has shown success in the clinical setting. The technique consists of a mutant adenovirus that selectively infects and kills only cells that are deficient in p53, such as tumor cells. (Lacking the E1B protein that shuts down p53, the mutant adenovirus can't reproduce in cells with normal p53; but it can replicate in and thus kill cells that do not have functioning p53. See diagram) ONYX has tested this adenovirus in a small number of patients with head and neck cancer who had not responded to surgery, radiation, and in some cases chemotherapy. The adenovirus treatment produced significant destruction of tumors in some patients and lesser improvement in several others. Scientists do not yet know if the tumor cells are dying because of direct viral assault or from attack by the immune system on virus-infected cells.
A different kind of biotherapy uses a type of molecule called a ribozyme, which is able to bind to and destroy RNA. NIDCR oral cancer researchers at SUNY in Syracuse have developed ribozymes that destroy the RNA of tumor-associated human papillomavirus and have devised a method for introducing them into cancer cells in vitro to inhibit tumor cell growth. Of major importance was their finding that the tumor suppressor protein, p53, usually absent in HPV-containing tumor cells, could be detected in the cells into which ribozymes had been introduced. These results imply that the ribozyme inhibited the HPV gene product(s) involved in the breakdown of p53. These studies provide a strong basis for current investigations designed to determine if ribozymes can inhibit tumor formation in an animal model by the administration of HPV-positive tumor cells.
Cell Suicide As Cancer Therapy?
Apoptosis, or cell 'suicide,' is a backup system that prevents runaway division by alerting a cell to DNA damage and initiating self-destruction. Although apoptosis is bad for the cell, it is ultimately good for the body, which this way rids itself of damaged genetic material. Learning more about apoptosis is key to fully understanding cancer, and ultimately to developing strategies based on harnessing this process as a cancer therapy.
At the University of Chicago, NIDCR- and NCI-funded scientists are studying whether alterations in the susceptibility of tumor cells to undergo apoptosis contribute to the development, progression, or recurrence of oral and pharyngeal cancer. Their current studies focus on the bcl-2 gene family. Within the family are genes that code for proteins that suppress cell death, such as bcl-2 and bcl-xl, while others promote apoptosis. So far, the scientists have correlated overexpression of bcl-xl in human oral cancer tissue with a poor prognosis, and overexpression of bcl-2 with a more hopeful outcome. These findings are consistent with their earlier work on breast cancer. Those studies showed that bcl-xl overexpression was associated with a higher tumor grade and increased number of positive lymph nodes, and tumors expressing bcl-2 were of a lower grade and a smaller size.
For their latest studies on bcl-xl, the scientists created a transgenic mouse model that overexpresses the protein in the mouth, throat, and skin. When the animals' skin was exposed to known carcinogens, approximately 70 percent of them developed invasive skin cancer, whereas only 18 percent of the control group developed the disease. The scientists are now beginning studies of the oral mucosa using a similar transgenic model. Can a cell be tricked into dying? Ultimately, the scientists hope to be able to answer this question as they learn more about the apoptotic process and the so-called 'cell survival genes' that code for proteins like bcl-xl.
A three-gene 'cocktail' is the focus of a unique gene therapy strategy set to be tested soon by NIDCR grantees at Johns Hopkins University. The herpes simplex virus thymidine kinase (HSV-tk) "suicide" gene and genes for two cytokines -- interleukin-2 (IL-2) and granulocyte macrophage colony stimulating factor (GM-CSF) -- will be delivered via an adenovirus into a mouse model of oral cancer. The scientists speculate the therapies will act synergistically. Here is why: The HSV-tk therapy causes oral cancer cells to commit 'suicide' in the presence of certain anti-herpetic drugs such as ganciclovir. As that occurs, the tumor cells release cellular debris and antigens recognized by immune cells. The HSV-tk/ganciclovir therapy, then, not only works to reduce tumor size, but also sets the stage for tumor-specific immune activity by IL-2 and GM-CSF. In turn, the two cytokines stimulate specific immune cells that are able to recognize and help destroy tumor cells.
Further along in the research pipeline is an apoptosis-based therapy using the p53 gene. Clinical investigators at the M.D. Anderson Cancer Center and Introgen Pharmaceuticals, Inc., recently completed a study on the safety of p53 gene therapy in a small number of patients with head and neck cancer. The study was a dose-escalation trial in which the investigators used an adenovirus to deliver normal p53 gene into the patients' tumors. All the patients had advanced, recurrent cancers of the head and neck and had failed conventional treatment. The researchers found that the gene therapy was not only free of serious side effects, it actually resulted in tumor regression in some patients. With its safety now documented, scientists can move the p53 treatment to the next stage of clinical testing.
Where Do We Go From Here?
Clearly, our exploration into the fundamental mechanisms of cancer must continue -- for every step in the cancer development process is a potential target for new therapies. Basic research has already paid off in many ways, showing us that specific classes of genes are involved in cancer development, that environmental factors can trigger genetic mutations, and that cancer cells spin out of control and proliferate unchecked. Within the next few years NIDCR studies on cell signaling, cell cycle regulation, tumor angiogenesis, and a myriad of other topics might further elucidate how cancer develops and spreads, information that is paramount to learning how to stop the disease.
We must also continue to educate -- spreading the word that many cases of oral cancer can be avoided by changing certain behaviors. Quitting tobacco use, stopping excessive drinking, and eating a diet rich in fresh fruits and vegetables are all things people can do now to reduce their risk of developing the disease. Clinicians, too, can help save lives by performing the simple head and neck examination, and by talking to patients about cancer's early warning signs.
Oral cancer is a disease whose survival rate has not improved appreciably in decades, a disease that has a high rate of second primary tumors, and a disease that leaves its mark on survivors in the form of facial disfigurement. Through basic, translational, clinical, and community-based research, and through public and professional education, NIDCR is continuing its fight against oral cancer, working to ensure that no one need ever suffer from this devastating disease.
------------------------------------------------------------------------------------------------------------------------------------------------------------------
Smoking and Your Mouth
The use of the word "smoking" and the phrase "good oral health" in the same sentence just doesn't go together.
Not only does smoking leave brown stains and sticky tar deposits on your teeth or dentures, but it contributes to halitosis (bad breath). It's not uncommon to see red inflammation on the palate (roof of the mouth) from the high temperatures generated by cigarette, cigar and pipe smoking.
Smoking is a major risk factor in periodontal (gum) disease. As shown by 20 years of research, smokers are two to three times more likely to develop periodontitis (bone loss). Tooth loss is much more prevalent than in non-smokers. Studies have shown a higher rate of dental implant failures for those who smoke.
Smoking is the leading cause of oral cancer. There are 9,000 deaths a year in the U.S. from oral cancer and tobacco use accounts for 75 percent of them.
Even second-hand smoke poses danger, especially for children. When children breathe in smoke, it can affect the development and eruption of their permanent teeth.
The good news is that "kicking the habit" greatly reduces the risk of developing oral cancer. After 10 years of cessation, the risk is similar to that of a non-smoker. There are a number of ways to stop without experiencing extreme withdrawal symptoms including the nicotine patch, nicotine gum and nicotine spray or inhaler.
------------------------------------------------------------------------------------------------------------------------------------------------------------------
Cancer Treatment
Chemotherapy and Your Mouth
Are You Being Treated With Chemotherapy for Cancer?
If so, this booklet can help you. While chemotherapy helps treat cancer, it can also cause other things to happen in your body called side effects. Some of these problems affect the mouth and could cause you to delay or stop treatment.
This booklet will tell you ways to help prevent mouth problems so you'll get the most from your cancer treatment.
To help prevent serious problems, see a dentist at least 2 weeks before starting chemotherapy.
How Does Chemotherapy Affect the Mouth?
Chemotherapy is the use of drugs to treat cancer. These drugs kill cancer cells, but they may also harm normal cells, including cells in the mouth. Side effects include problems with your teeth and gums; the soft, moist lining of your mouth; and the glands that make saliva (spit).
It's important to know that side effects in the mouth can be serious.
- The side effects can hurt and make it hard to eat, talk, and swallow.
- You are more likely to get an infection, which can be dangerous when you are receiving cancer treatment.
- If the side effects are bad, you may not be able to keep up with your cancer treatment. Your doctor may need to cut back on your cancer treatment or may even stop it.
What Mouth Problems Does Chemotherapy Cause?
You may have certain side effects in your mouth from chemotherapy. Another person may have different problems. The problems depend on the chemotherapy drugs and how your body reacts to them. You may have these problems only during treatment or for a short time after treatment ends.
Painful mouth and gums.
Dry mouth.
Burning, peeling, or swelling tongue.
Infection.
Change in taste.
Why Should I See a Dentist?
You may be surprised that your dentist is important in your cancer treatment. If you go to the dentist before chemotherapy begins, you can help prevent serious mouth problems. Side effects often happen because a person's mouth is not healthy before chemotherapy starts. Not all mouth problems can be avoided but the fewer side effects you have, the more likely you will stay on your cancer treatment schedule.
It's important for your dentist and cancer doctor to talk to each other about your cancer treatment. Be sure to give your dentist your cancer doctor's phone number.
When Should I See a Dentist?
You need to see the dentist at least 2 weeks before chemotherapy begins. If you have already started chemotherapy and didn't go to a dentist, see one as soon as possible.
What Will the Dentist and Dental Hygienist Do?
Check your teeth.
Take x-rays.
Take care of mouth problems.
Show you how to take care of your mouth to prevent side effects.
What Can I Do To Keep My Mouth Healthy?
You can do a lot to keep your mouth healthy during chemotherapy. The first step is to see a dentist before you start cancer treatment. Once your treatment starts, it's important to look in your mouth every day for sores or other changes. These tips can help prevent and treat a sore mouth
Keep your mouth moist.
Drink a lot of water.
Suck ice chips.
Use sugarless gum or sugar-free hard candy.
Use a saliva substitute to help moisten your mouth.
Clean your mouth, tongue, and gums.
Brush your teeth, gums, and tongue with an extra-soft toothbrush after every meal and at bedtime. If brushing hurts, soften the bristles in warm water.
Use a fluoride toothpaste.
Don't use mouthwashes with alcohol in them.
Floss your teeth gently every day. If your gums bleed and hurt, avoid the areas that are bleeding or sore, but keep flossing your other teeth.
Rinse your mouth several times a day with a solution of 1/4 teaspoon baking soda and 1/8 teaspoon salt in one cup of warm water. Follow with a plain water rinse.
Dentures that don't fit well can cause problems. Talk to your cancer doctor or dentist about your dentures.
If Your Mouth Is Sore, Watch What You Eat and Drink:
Choose foods that are good for you and easy to chew and swallow.
Take small bites of food, chew slowly, and sip liquids with your meals.
Eat soft, moist foods such as cooked cereals, mashed potatoes, and scrambled eggs.
If you have trouble swallowing, soften your food with gravy, sauces, broth, yogurt, or other liquids.
Call Your Doctor or Nurse When Your Mouth Hurts:
Work with them to find medicines to help control the pain.
If the pain continues, talk to your cancer doctor about stronger medicines
Remember To Stay Away From :
Sharp, crunchy foods, like taco chips, that could scrape or cut your mouth.
Foods that are hot, spicy, or high in acid, like citrus fruits and juices, which can irritate your mouth.
Sugary foods, like candy or soda, that could cause cavities.
Toothpicks, because they can cut your mouth.
All tobacco products.
Alcoholic drinks.
------------------------------------------------------------------------------------------------------------------------------------------------------------------
Do Children Get Mouth Problems Too?
Chemotherapy causes other side effects in children, depending on the child's age.
Problems with teeth are the most common. Permanent teeth may be slow to come in and may look different from normal teeth. Teeth may fall out. The dentist will check your child's jaws for any growth problems.
Before chemotherapy begins, take your child to a dentist. The dentist will check your child's mouth carefully and pull loose teeth or those that may become loose during treatment. Ask the dentist or hygienist what you can do to help your child with mouth care.
Remember:
Visit your dentist before your cancer treatment starts.
Take good care of your mouth during treatment.
Talk regularly with your cancer doctor and dentist about any mouth problems you have.
------------------------------------------------------------------------------------------------------------------------------------------------------------------
Head and Neck Radiation Treatment and Your Mouth
Are You Being Treated With Radiation for Cancer in Your Head or Neck?
If so, this booklet can help you. While head and neck radiation helps treat cancer, it can also cause other things to happen in your mouth called side effects. Some of these problems could cause you to delay or stop treatment.
This booklet will tell you ways to help prevent mouth problems so you'll get the most from your cancer treatment.
To help prevent serious problems, see a dentist at least 2 weeks before starting radiation.
How Does Head and Neck Radiation Affect the Mouth?
Doctors use head and neck radiation to treat cancer because it kills cancer cells. But radiation to the head and neck can harm normal cells, including cells in the mouth. Side effects include problems with your teeth and gums; the soft, moist lining of your mouth; glands that make saliva (spit); and jaw bones.
It's important to know that side effects in the mouth can be serious:
The side effects can hurt and make it hard to eat, talk, and swallow.
You are more likely to get an infection, which can be dangerous when you are receiving cancer treatment.
If the side effects are bad, you may not be able to keep up with your cancer treatment. Your doctor may need to cut back on your cancer treatment or may even stop it.
What Mouth Problems Does Head and Neck Radiation Cause?
You may have certain side effects in your mouth from head and neck radiation. Another person may have different problems. Some problems go away after treatment. Others last a long time, while some may never go away.
Dry mouth.
A lot of cavities.
Loss of taste.
Sore mouth and gums.
Infections.
Jaw stiffness.
Jaw bone changes.
Why Should I See a Dentist?
You may be surprised that your dentist is important in your cancer treatment. If you go to the dentist before head and neck radiation begins, you can help prevent serious mouth problems. Side effects often happen because a person's mouth is not healthy before radiation starts. Not all mouth problems can be avoided but the fewer side effects you have, the more likely you will stay on your cancer treatment schedule.
It's important for your dentist and cancer doctor to talk to each other before your radiation treatment begins. Be sure to give your dentist your cancer doctor's phone number.
When Should I See a Dentist?
You need to see the dentist at least 2 weeks before your first radiation treatment. If you have already started radiation and didn't go to a dentist, see one as soon as possible.
What Will the Dentist and Dental Hygienist Do?
Check your teeth.
Take x-rays.
Take care of mouth problems.
Show you how to take care of your mouth to prevent side effects.
Show you how to prevent and treat jaw stiffness by exercising the jaw muscles 3 times a day. Open and close the mouth as far as possible (without causing pain) 20 times.
What Can I Do To Keep My Mouth Healthy?
You can do a lot to keep your mouth healthy during chemotherapy. The first step is to see a dentist before you start cancer treatment. Once your treatment starts, it's important to look in your mouth every day for sores or other changes. These tips can help prevent and treat a sore mouth:
Keep your mouth moist.
Drink a lot of water.
Suck ice chips.
Use sugarless gum or sugar-free hard candy.
Use a saliva substitute to help moisten your mouth.
Clean your mouth, tongue, and gums.
Brush your teeth, gums, and tongue with an extra-soft toothbrush after every meal and at bedtime. If brushing hurts, soften the bristles in warm water.
Use a fluoride toothpaste.
Don't use mouthwashes with alcohol in them.
Floss your teeth gently every day. If your gums bleed and hurt, avoid the areas that are bleeding or sore, but keep flossing your other teeth.
Rinse your mouth several times a day with a solution of 1/4 teaspoon baking soda and 1/8 teaspoon salt in one cup of warm water. Follow with a plain water rinse.
Dentures that don't fit well can cause problems. Talk to your cancer doctor or dentist about your dentures.
If Your Mouth Is Sore, Watch What You Eat and Drink.
Choose foods that are good for you and easy to chew and swallow.
Take small bites of food, chew slowly, and sip liquids with your meals.
Eat soft, moist foods such as cooked cereals, mashed potatoes, and scrambled eggs.
If you have trouble swallowing, soften your food with gravy, sauces, broth, yogurt, or other liquids.
Call Your Doctor or Nurse When Your Mouth Hurts:
Work with them to find medicines to help control the pain.
If the pain continues, talk to your cancer doctor about stronger medicines.
Remember To Stay Away From:
Sharp, crunchy foods, like taco chips, that could scrape or cut your mouth.
Foods that are hot, spicy, or high in acid, like citrus fruits and juices, which can irritate your mouth.
Sugary foods, like candy or soda, that could cause cavities.
Toothpicks, because they can cut your mouth.
All tobacco products.
Alcoholic drinks.
Do Children Get Mouth Problems Too?
Head and neck radiation causes other side effects in children, depending on the child's age.
Problems with teeth are the most common. Permanent teeth may be slow to come in and may look different from normal teeth. Teeth may fall out. The dentist will check your child's jaws for any growth problems.
Before radiation begins, take your child to a dentist. The dentist will check your child's mouth carefully and pull loose teeth or those that may become loose during treatment. Ask the dentist or hygienist what you can do to help your child with mouth care.
Remember:
Visit your dentist before your head and neck radiation treatment starts.
Take good care of your mouth during treatment.
Talk to your dentist about using fluoride gel to help prevent all the cavities that head and neck radiation causes.
Talk regularly with your cancer doctor and dentist about any mouth problems you have during and after head and neck radiation treatment.
Content provided by NIH | | Send this story to a friend | Printer Friendly |
|
|
|
