Oral cancer is cancer of the lips, mouth, tongue, tonsil, and throat; there are two major types of oral cancer: oral cavity cancer and oropharyngeal cancer (1). Oral cancer has a high prognosis when they are identified early and intervention is started early. According to the National Cancer Institute’s Surveillance, Epidemiology and End Results Program (SEER), the estimated incidences of Oral cancer in 2017 is 49,670 new cases representing 2.9% of all new cancers and 9,700 deaths representing 1.6% of all cancer deaths. In 2014, the prevalence of people living in the US with oral cavity or pharynx cancer was estimated to be 346,902 (2). Rates of new cases of oral and pharynx cancer increased slightly over 10 years from 2005 to 2015 on an average of 0.7% cases per 100,000 populations; however, the mortality rate was stable at a rate of 2.5% cases per 100,000 populations (2). The major risk factors for oral cancer are tobacco use, heavy alcohol use and/or individuals with chronic HPV infection. According to the American Cancer Society (ACS), men are twice as likely to get oral cancer than women and the prevalence is evenly distributed among all ethnicity at an average age of 62 years old (3).
The composition of the oral cavity is mainly squamous cells; therefore, cancers of the mouth are often referred to as squamous carcinoma (4). The oral cavity includes lips, the inside lining of the lips and the cheeks, the teeth, the gum, the front two-thirds of the tongue, the floor of the mouth below the tongue, bony roof of the mouth (aka hard palate), area behind the wisdom teeth. The oropharynx is the part of the throat behind the mouth starting from where the oral cavity stops (the back third of the tongue, tonsils, and the side and back walls of the throat) (you can refer to picture 1) (1). Both the oral cavity and the oropharynx help an individual breath, talk, eat, chew, and swallow. Tumors are abnormal tissue growth resulting from the deregulated proliferation of cells. The tumor can be classified as benign growth (not cancerous- do not invade or spread to other parts of the body), precancerous (harmless that can turn into cancer over time) or cancerous (can grow and invade into nearby tissues or spread to other parts of the body) (1). The precancerous lesions are Leukoplakia (white or gray patch), erythroplakia (flat or slightly raised red area that often bleeds easily if its scraped) or erythroleukoplakia (patch with both red and white areas). They are often caused by excessive smoking, chewing tobacco, or poorly fitted dentures that rub against the tongue or the inside cheeks causing tissue changes. Erythroplakia and Erythroleukoplakia are the more concerning precancerous lesions because they often develop into cancerous cells. These precancerous lesions are not the only precursors for all types of oral cancers.
Although squamous cell carcinoma is the common type of oral cancer, there are other types of cancers that occur in the oral cavity and oropharynx. The squamous cell carcinoma (makeup at least 90% of the cancers in the oral cavity and oropharynx) first appear as flat, scale-like cells that line the mouth and throat (1). When these cells have not broken through the basal membrane that lines the epithelial cells, they are called carcinoma in situ. Once the cancer cell growth breaks through the basal membrane, the cancer is considered invasive and the spread to other parts of the body is likely (metastasized) which will require more comprehensive cancer treatment with decreased prognosis. Verrucous carcinoma is another type of squamous carcinoma that occurs less frequently (less than 5%). It is slow growing and rarely spread to other parts of the body, but is strongly recommended to remove immediately with a wide range of surrounding normal tissues because cancerous cells are intermingled with normal cells that make it difficult to detect in biopsies and if untreated can become invasive (1). The other types are minor salivary gland carcinomas (start in the glands that line the mouth and throat- that includes adenoid cystic carcinoma, mucoepidermoid carcinoma, and polymorphous low-grade adenocarcinoma), and lymphomas (cancers in the tonsils and base of the tongue). It is difficult to know what causes these tissue changes that result in each cancer, however, there are risk factors that are associated.
The common risk factors are heavy alcohol use, tobacco use, and virus infection. The risk factors can cause an alteration in the DNA also known as DNA mutation. These mutations can change how a cell grows or divide. By changing these mechanisms, cells can grow out of control resulting in cancerous tumors. Tobacco and alcohol damage the cells that line the mouth and throat needing rapid repair and growth. If the cell DNA is altered, normal cells can be transformed into cancerous cells (8). Tobacco is said to have at least 30 chemicals that can damage DNA directly and cause cancer; the most harmful is tobacco-specific nitrosamine (TSNAs) (8). Alcohol does not appear to damage the DNA directly but helps other DNA damaging chemicals to enter into the cells (scale-like chemicals from tobacco). A virus known as Human Papillomavirus (HPV) infection has been linked with certain types of oral cancer. The virus produces proteins E6 and E7 that interferes with the host’s genes that regulate tumor suppressor genes (8). Without these tumor suppressor genes, the cell growth will be unregulated and become cancerous. The cellular changes can be manifested in varied symptoms.
Symptoms of oral cancer can vary. Symptoms include: difficulty chewing, swallowing (dysphagia), epigastric discomfort, delayed gastric emptying (7). Other symptoms include, sore in the mouth or on the lip that does not heal (ie. oral infection), Red or white patch on the gums, tongue, tonsil, or lining of the mouth, lump on the lip, mouth, neck, or throat (ie. ulceration) or a feeling of thickening in the cheek, persistent sore throat or feeling that something is caught in the throat, hoarseness or change in voice, numbness of the mouth or tongue, pain or bleeding in the mouth, difficulty chewing, swallowing, or moving the jaws or tongue, ear and/or jaw pain, chronic bad breath, changes in speech, loosening of teeth or toothache, dentures that no longer fit, unexplained weight loss, fatigue, loss of appetite, especially when prolonged; this may happen during the later stages of the disease (5). The American Cancer Society (ACS) provided early signs and symptoms of cancer in an acronym CAUTION (Change in bowel or bladder habits, A sore that does not heal, Unusual bleeding or discharge, Thickening or lump in breast or elsewhere, Indigestion or difficulty in swallowing or chewing, Obvious change in a wart or mole, Nagging cough or hoarseness (7). The possible nutritional consequences for these symptoms are anorexia, a decreased variety of foods, weight loss, and changes in food texture (7). There are also many who are asymptomatic making it difficult to diagnose if a dentist is not seen regularly for a routine examination.
There are multiple tests used to diagnose oral cancer and determine the stages to assess appropriate treatments. A biopsy is the most commonly utilized diagnostic test for oral cancer; however, if a biopsy is not possible other tests are available. There are multiple factors used to determine which tests are most appropriate. The factors considered are the type of cancer suspected, signs and symptoms, age and medical conditions, and the results of earlier medical tests (9). Many of the diagnostic tests can be used in conjunction with one another. The diagnostic tests include: Physical examination (examine neck, lips, gums, cheeks, area behind nose, the larynx, and the lymph nodes of the neck), Endoscopy (think flexible tube with light and view lens is placed into the back of the mouth to see the back of the throat in detail), biopsy (removal of small amount of tissue for examination under a microscope), oral brush biopsy (Noninvasive use of small brush to gather cell samples for analysis. For positive results, this test will be used in conjunction with traditional biopsy), x-ray (images of the structures of the mouth for abnormal growth), barium swallow (used to look at oropharynx to assess changes in the structure of the oral cavity and throat as well as examine the function of the stomach), computed tomography scan (3-D picture of the inside of the body using x-ray, to determine any abnormalities or tumors. This test can also measure the tumor size, assess accessibility for tumor removal, and help determine if the cancer cells spread to lymph nodes.), Magnetic resonance imaging (uses magnetic fields to produce images of the soft tissues such as tonsils and the base of the tongue. This test is also used to measure the tumor size.), Ultrasound (use sound waves to create images of the internal organs; this test can help determine if cancer has spread to the lymph nodes in the neck.), and Positron emission tomography (usually used in conjunction with CT scan to create pictures of the organs and the tissues inside the body. A radioactive sugar is used to determine abnormal sugar metabolism indicative of abnormal cell growth -cancerous cells) (9).
Once cancer is diagnosed through series of histologic and imaging diagnostic tests, the conventional modalities for treatment include, surgery, radiation therapy, and chemotherapy depending on the type and stage of cancer, possible side effects, and the patient’s preferences and overall health (7). In many cases, a team of multidisciplinary doctors will work together to preserve the function of the oral nerves, organs, and tissues. They also work together to not only treat cancer, but they are also cognizant of an individual’s quality of life such as how an individual feel, looks, talks, eats, and breathes. The team of doctors is also supported by axillary support such as oncology nurses, social workers, pharmacists, counselors, dietitians, and others. Surgery aims for complete removal of cancerous tissues. The side effects of surgery are often caused by swelling making breathing difficult. It can also result in permanent loss of voice or impaired speech, difficulty chewing, swallowing, or talking, numbness of the ear; weakness raising the arm above the head; lack of movement in the lower lip and facial disfiguration. Surgery can also affect the function of the thyroid gland, especially with total laryngectomy. Chemotherapy is the use of cytotoxic agents such as alkylating agents, antimetabolites, antitumor antibiotics, nitrosoureas, and plant alkaloids to systemically treat cancer (7). The common side effects of chemotherapy are nausea, vomiting, and anorexia (7). Due to alterations in chewing, swallowing, salivation, and taste acuity for cancer patients, extensive dental decay, osteoradionecrosis, and infection occurs (7). Radiation therapy uses high-energy (ionizing radiation) in multiple fractionated doses, or radioactive chemicals to treat cancer (7). Radiation therapy can cause tooth decay, speech impairment and/or difficulty swallowing, and hearing may be affected for those who receive radiation therapy close to the head causing nerve damage, hypothyroidism (thyroid gland slows down causing patients to be tired and sluggish), redness or skin irritation to the treated area, dry mouth or thickened saliva from damaged salivary glands, bone pain, nausea, fatigue, mouth sores, sore throat, difficulty opening mouth, and loss of appetite (12). Other alternative therapies are Immunotherapy (designed to boost the body’s natural defense against cancer) and targeted therapy (targets cancer’s specific gene, proteins or the tissue environment that contributes to cancer growth and survival). Immunotherapy hopes to improve, target and restore the immune system function (12). There are currently 2 immunotherapy drugs approved by U.S. Food and Drug Administration (FDA) to treat people with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has not been successful with platinum-based chemotherapy; they are Pembrolizumab (Keytruda) and nivolumab (Opdivo) (12). In cancer research there are many ways to identify the genes, proteins expressed and other characteristics of the tumor to effectively treat cancer. Currently, there is only one antibiotic that is targeted for epidermal growth factor receptor (EGRF) currently approved by FDA; Cetuximab. Another alternative treatment is antiangiogenic therapy which prevents or reduces the growth of new blood vessels that feeds tumor cells for its growth.
Medical Nutritional Therapy is another alternative therapy that is commonly used in conjunction with standard medical therapy. The most common problems oral cancer patients encounter is their inability to meet the required energy and protein needs orally, therefore feeding tube (gastrostomy) is usually considered as an alternate method for food intake (7). This could be complete gastrostomy feeding or supplemental. A study in 2018 further explored cancer patients unintentional weight loss and malnutrition at diagnosis, during oncologic treatment, and after the end of therapy because of reduction in eating ability and aimed to assess the effectiveness of nutritional intervention in maintaining basal nutritional conditions (13). Nutritional status, nutritional intake (oral and artificial), and body composition were evaluated on 35 patients by expert dietitian on newly diagnosed or recurrent head and neck cancer patients > 18 years old at initial, 1, 3, and 6 months visit. The study demonstrated the need to increase the daily intake from 30 kcal/kg to 35 kcal/kg for patients who undergo CTRT to maintain stable body weight and phase angle by means of enteral and oral feeding. These findings are important because body composition deterioration before, during and after CTRT is associated with worsening quality of life, worse prognosis and poor survival (13). Studies have also shown added oral nutritional supplements to nutritional plan help improve nutritional intake, help maintain body weight, and improve outcomes (10). Oral nutritional supplements are fortified beverages that provide extra calories, protein and essential vitamins and minerals (10). A typical single serving is said to provide 230-350 calories, 9-13 grams of proteins, and 24 or more essential vitamins and minerals (10). The oncology nutrition from the Academy of Nutrition and Dietetics suggests ideas to help increase nutrition by trying different varieties of oral nutritional supplements that are appealing, experiment with different flavors and rotate to avoid getting tired of the same flavor, if “milk-like” is not appealing try “juice-like” supplements, try adding the supplement to usual foods such as adding to coffee or cereal, try to make milkshakes or smoothies with the supplement, or try freezing the supplement to make it more similar to ice cream (10). According to the Academy of Nutrition and Dietetics, the primary recommendation for cancer prevention is weight control, which includes eating more fruits and vegetables and cutting back on red and processed meats (11). The American Institute of Cancer Research’s general recommendations for “cancer fighting foods” include, varied diet high in variety of vegetables, fruits, whole grains and beans, brightly colored and strongly flavored vegetables and fruits which are often the best sources of phytochemicals, and in general food sources because they are more easily absorbed than phytochemical supplements (11). In recent studies, Green Tea (GT) catechins such as Epigallocatechin Gallate (EGCG) played a role in improving health by preventing a number of cancers including lung and oral cancer (14). Although there are a number of studies demonstrating the effect of GT in preventing cancers in the oral cavity, lung, digestive tract, skin, prostate and breast in rodents by detoxification of carcinogen oxidizing agents, changes in gene expression, induction of cell cycle arrest and apoptosis, anti-inflammatory actions, and inhibition of tumor-associated angiogenesis scientist have not been able to replicate these results in people. This study hopes to examine the counteractively of tobacco-induced changes in the mRNA and microRNA with GT effects of minimizing the effects of smoking by decreasing inflammation and increasing DNA repair capabilities. The results showed changes in the microbiome after GT exposure which can affect carcinogenesis, but the effects of oral epithelial mRNA expression in humans were inconsistent to make any conclusions (14). More well-designed studies are needed in pursuit of effective nutraceuticals.


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