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Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers.
Some studies in Australia, Brazil and Germany pointed to alcohol-containing mouthwashes as also being potential causes. The claim was that constant exposure to these alcohol-containing rinses, even in the absence of smoking and drinking, leads to significant increases in the development of oral cancer. However, studies conducted in 1985, 1995, and 2003 summarize that alcohol-containing mouth rinses are not associated with oral cancer. In a March 2009 brief, the American Dental Association said "the available evidence does not support a connection between oral cancer and alcohol-containing mouthrinse". A 2008 study suggests that acetaldehyde (a breakdown product of alcohol) is implicated in oral cancer, but this study specifically focused on abusers of alcohol and made no reference to mouthwash. Any connection between oral cancer and mouthwash is tenuous without further investigation.
People with HPV-mediated oropharyngeal cancer tend to have higher survival rates. The prognosis for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers.
Infection with human papillomavirus (HPV), particularly type 16 (there are over 180 types), is a known risk factor and independent causative factor for oral cancer. A fast-growing segment of those diagnosed does not present with the historic stereotypical demographics. Historically that has been people over 50, blacks over whites 2 to 1, males over females 3 to 1, and 75% of the time people who have used tobacco products or are heavy users of alcohol. This new and rapidly growing sub population between 30 and 50 years old, is predominantly nonsmoking, white, and males slightly outnumber females. Recent research from multiple peer-reviewed journal articles indicates that HPV16 is the primary risk factor in this new population of oral cancer victims. HPV16 (along with HPV18) is the same virus responsible for the vast majority of all cervical cancers and is the most common sexually transmitted infection in the US. Oral cancer in this group tends to favor the tonsil and tonsillar pillars, base of the tongue, and the oropharynx. Recent data suggest that individuals that come to the disease from this particular cause have a significant survival advantage, as the disease responds better to radiation treatments than tobacco caused disease.
Around 75% of cases are caused by alcohol and tobacco use.
Tobacco smoke is one of the main risk factors for head and neck cancer and one of the most carcinogenic compounds in tobacco smoke is acrylonitrile. (See Tobacco smoking). Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic. DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA.
However, cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.
The ex-smoker's risk for squamous cell cancer of the head and neck begins to approach the risk in the general population twenty years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention.
Smokeless tobacco is cause of oral and pharyngeal cancers (oropharyngeal cancer). Cigar smoking is an important risk factor for oral cancers as well.
Other environmental carcinogens suspected of being potential causes of head and neck cancer include occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. Use of marijuana, especially while younger, is linked to an increase in squamous-cell carcinoma cases while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma.
Since many, if not most, anal cancers derive from HPV infections, and since the HPV vaccine before exposure to HPV prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.
On 22 December 2010, the U.S. Food and Drug Administration approved Gardasil vaccine to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years. The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.
Treatment of hypopharyngeal cancer depends on the prognosis (chance of recovery), age, stage, and general health of the patient. Because hypopharyngeal cancer is often advanced at the time of diagnosis, treatment also depends on the overall goal. The goal may simply be to keep the patient talking, eating, and breathing normally.
Treatment usually begins with surgery and then a course of radiation for cancer that has progressed past Stage I. For cancer that is advanced, which is typical of hypopharyngeal cancer, neoadjuvant chemotherapy may be used. This is performed by administering chemotherapy before surgery. Neoadjuvant chemotherapy in conjunction with radiation and surgery has yielded the best results in patients with Stage III and Stage IV cancers.
Factors that contribute to the development of hypopharyngeal cancer include:
- Smoking
- Chewing tobacco
- Heavy alcohol use
- Poor diet
Smoking, like lung cancer, can cause hypopharyngeal cancer because it contains carcinogens that alter the DNA or RNA in a dividing cell. These alterations may change a normal DNA sequence to an oncogene, a gene that causes cancer after exposure to a carcinogen.
Squamous cells, a type of cell that lines hollow organs like the throat, mouth, lungs, and outer layer of skin, are particularly vulnerable when exposed to cigarette smoke.
Chewing tobacco can have the same effects as smoking and is also linked to hypopharyngeal cancer. The chewing tobacco is placed into the mouth, leaving it exposed to enzymes, like amylase, which partly digests the carcinogenic material. Saliva is swallowed, along with the cancer-promoting material, which passes through the hypopharynx on its way to the esophagus.
Heavy alcohol use is linked to Hypopharyngeal Cancer as well. Alcohol damages the lining of the hypopharynx, increasing the amount of chemicals that are allowed to seep into the underlying membranes. Heavy alcohol use is also associated with nutritional deficiencies.
A disease called Plummer-Vinson syndrome, a genetic disorder that causes a long-term iron deficiency, may also lead to Hypopharyngeal Cancer. Other factors like a deficiency in certain vitamins also appear to contribute to this type of cancer.
The risk factors that can increase the risk of developing oropharyngeal cancer are:
- Smoking and chewing tobacco
- Heavy alcohol use
- A diet low in fruits and vegetables
- Chewing betel quid, a stimulant commonly used in parts of Asia
- Mucosal infection with human papilloma virus (HPV) (HPV-mediated oropharyngeal cancer)
- HPV infection
- Plummer-Vinson syndrome
- Poor nutrition
- Asbestos exposure
Certain genetic changes including: P53 mutation and CDKN2A (p16) mutations.
High-risk lesions:
- Erythroplakia
- Speckled erythroplakia
- Chronic hyperplastic candidiasis
Medium-risk lesions:
- Oral submucosal fibrosis
- Syphilitic glossitis
- Sideropenic dysphagia (or Paterson-Kelly-Brown syndrome)
Low-risk lesions:
- Oral lichen planus
- Discoid lupus erythematosus
- Discoid keratosis congenita
10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.
The treatment for tonsil carcinoma includes the following methods:
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
While less studies have been completed examining deintensification in this setting, than in primary radical radiation for this cancer (see below), it is an area of active investigation. In one single institution study, a decision was made to reduce the radiation dose in high risk patients with HPV+OPC from 66 to 60 Gy, corresponding to the actual evidence, and follow up has shown no decrease in cancer control. Current trials, both in North America and Europe (such as ECOG 3311 and PATHOS) use 50 Gy as the comparison arm. The comparator of 50 Gy was chosen on the grounds of (i) the exquisite sensitivity of HPV+OPC to radiation, both "in vitro" and "in vivo"; ECOG 1308 showing excellent disease control at 54 Gy; and data suggesting that 50 Gy in 1.43 Gy (iso-effective dose 43 Gy in 2.0 Gy was sufficient to electively treat the neck. Other studies are evaluating doses as low as 30 Gy in high risk cases.
Chemotherapy has been used concurrently with radiation in this setting, as in primary treatment with radical radiation, particularly where pathological features indicated a higher risk of cancer recurrence. a number of studies have suggested that this does not improve local control, although adding toxicity.
The probability of xerostomia at one year increases by 5% for every 1Gy increase in dose to the parotid gland. Doses above 25–30 Gy are associated with moderate to severe xerostomia. Similar considerations apply to the submandibular gland, but xerostomia is less common if only one parotid gland is included in the radiated field and the contralateral submandibular gland is spared (less than 39 Gy) In the same manner, radiation dose to the pharyngeal constrictor muscles, larynx, and cricopharyngeal inlet determine the risk of dysphagia (and hence dependence on gastrostomy tube feeds). The threshold for this toxicity is volume-dependent at 55–60 Gy, with moderate to severe impairment of swallowing, including aspiration, stricture and feeding tube dependence above a mean dose of 47 Gy, with a recommended dose to the inferior constrictor of less than 41 Gy. Dose-toxicity relationships for the superior and middle constrictors are steep, with a 20% increase in the probability of dysphagia for each 10 Gy. For late dysphagia, threshold mean total constrictor doses, to limit rates of greater than or equal to grade 2 and 3 below 5% were 58 and 61 Gy respectively. For grade 2 dysphagia, the rate increased by 3.4% per Gy. Doses above 30 Gy to the thyroid are associated with moderate to severe hypothyroidism. Subjective, patient-reported outcomes of quality of life also correlate with radiation dose received.
Altered fractionation schemes, such as RTOG 9003 and RTOG 0129 have not conferred additional benefit. Radiation dose recommendations were largely determined empirically in clinical studies with few HPV+OPC patients, and have remained unchanged for half a century, making it difficult to determine the optimum dose for this subgroup. A common approach uses 70 Gy bilaterally and anteriorly, such as RTOG 9003 (1991–1997) and RTOG 0129 (2002–2005). For lateralized tonsil cancer unilateral neck radiation is usually prescribed, but for tongue base primaries bilateral neck radiation is more common, but unilateral radiation may be used where tongue base lesions are lateralised.
Getting rid of "H. pylori" in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.
Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.
Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made.
Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.
Current dietary recommendations to prevent colorectal cancer include increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat and processed meats. Higher physical activity is also recommended. Physical exercise is associated with a modest reduction in colon but not rectal cancer risk. High levels of physical activity reduce the risk of colon cancer by about 21%. Sitting regularly for prolonged periods is associated with higher mortality from colon cancer. The risk is not negated by regular exercise, though it is lowered. The evidence for any protective effect conferred by fiber and fruits and vegetables is, however, poor. The risk of colon cancer can be reduced by maintaining a normal body weight.
Cancer of the stomach, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally. Eastern Asia (China, Japan, Korea, Mongolia) is a high-risk area for gastric cancer, and North America, Australia, New Zealand and western and northern Africa are areas with low risk. The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. Important factors that may contribute to the development of gastric cancer include diet, smoking and alcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example, "Helicobacter pylori" or Epstein-Barr virus) and pernicious anemia. Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.
Laboratory cats have been used in research for a wide range of diseases including stroke and diabetes to AIDS. Less than 1% of research on animal illnesses have been dedicated to cats.
Despite opposition from organizations such as those advocating animal rights, controversial animal testing is still used in cancer research centers. These research practices are continually being conducted on the basis that its benefits to humans outweigh the costs to humans, despite the unfair costs to innocent non-human animals. In some US states, animal testing laboratories get some of their feline test subjects from animal shelters.
According to Kim Sterling, associate teaching professor of oncology at the University of Missouri College of Veterinary Medicine, the use of small animals in predicting human health care procedures is of significant benefit to humans because they are affected in similar, but not exactly the same, ways by the same diseases. This is the same analogy used in reference to cats and their unwilling role in advancing human cancer treatment research.
It is research like this that has led to a potential link between cat parasites and brain cancer in humans. Cats carry the parasite toxoplasma gondii. According to research ecologist Kevin Lafferty, of the University of California, Santa Barbara, this parasite is known to “behave in ways that could stimulate cells towards cancerous states”.
Therefore, research on cats with this parasite can help to better understand the risks of brain cancer for humans in contact with such cats.
Cats have also been used to further studies in the field of Cancer stem cell research. Small animals, like cats, experience faster rates of cancer development. As a result, they are good preclinical models for understanding processes like immortalization and its role in promoting cancerous tumors. The absence of immortalization means a cell can no longer undergo malignant transformation. Since these transformations are the basis for cancerous cell reproduction, this research can prove useful for future cancer treatments and understanding how to stop the spread of cancer in the body.
However, feline cancer research is not limited to what laboratory cats can do for other animals, there is also research being done by humans to see what can be done to improve treatment options for feline cancer. Advances, though slower than that in other animals, are being made in the field of feline cancer. This includes advances in chemotherapy research, immunization protocols and radiation therapy. In addition, there are clinical trials offering trial research treatment options for cats with cancer.
One of such treatments is the cat's claw. Although they share the same name, the cat’s claw (also known as "Uncaria tomentosa" or uña de gato) refers not to the animal cat but to a native plant of the Amazon Rainforest in Peru, South America. Cat's claw is still under research for its immunotherapic, antiproliferative abilities in suppressing cancer proliferation in humans; however, it has been deemed suitable for cat cancer treatment.
Nonetheless, feline cancer research into this, as well as other treatment options, remains an ongoing process.
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer. It is not recommended in those at average risk. There is tentative evidence for calcium supplementation, but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer.
The prevention of feline cancer mainly depends on the cat's diet and lifestyle, as well as an ability to detect early signs and symptoms of cancer prior to advancement to a further stage. If cancer is detected at an earlier stage, it has a higher chance of being treated, therefore lessening the chances of fatality. Taking domesticated cats for regular checkups to the veterinarian can help spot signs and symptoms of cancer early on and help maintain a healthy lifestyle. Further, due to advancements in research, prevention of certain types of feline illnesses remains possible. A widely known preventative of feline leukemia virus is the vaccine which was created in 1969. Subsequently, an immunofloures-cent antibody (IFA) test for the detection of FeLV in the blood of infected cats was formulated. The IFA test was mainly used to experiment the chances of felines being exposed to cancer. The results showed that 33% of cats who were exposed to FeLV related diseases were at a higher risk for acquiring it, while the cats that were left unexposed were left unaffected. FeLV is either spread through contagion or infection and once infected it is possible for cats to stay that way for the rest of their lives.
Interaction with other Cats
Interaction with other cats with strains or diseases related to FeLV can be a great risk factor for cats attaining FeLV themselves. Therefore, a main factor in prevention is keeping the affected cats in quarantine from the unaffected cats. Stray cats, or indoor/outdoor cats have been shown to be at a greater risk for acquiring FeLV, since they have a greater chance of interacting with other cats. Domesticated cats that are kept indoors are the least vulnerable to susceptible diseases.
Vaccines
Vaccines help the immune system fight off disease causing organisms, which is another key to prevention. However, vaccines can also cause tumors if not given properly. Vaccines should be given in the right rear leg to ease tumor removal process. Vaccines given in the neck or in between the shoulder blades are most likely to cause tumors and are difficult to remove, which can be fatal to cats. Reducing the number of vaccinations given to a cat may also decrease the risk for it developing a tumor.
Spaying and Neutering
Spaying and neutering holds many advantages to cats, including lowering the risk for developing cancer. Neutering male cats makes them less subjected to testicular cancer, FeLV, and FIV. Spaying female cats lowers the risk for mammary cancer, ovarian, or uterine cancer, as it prevents them from going into heat. Female cats should be spayed before their first heat, as each cycle of heat creates a greater risk for mammary cancer. Spaying a female cat requires the removal of the ovaries and uterus, which would eliminate their chances of developing cancer in these areas.
Exposure to Sun
The risk of skin cancer increases when a cat is exposed to direct sunlight for prolonged periods. White cats, or cats with white faces and ears, should not be allowed out on sunny days. Between the hours of 10:00 am to 4:00 pm, it is recommended to keep domesticated cats indoors, as the sun is at its highest peak between these times. Sun block is also available for cats, which can help prevent skin irritation, and a veterinarian should be contacted to find out which brands are appropriate and to use on cats.
Exposure to Secondhand Smoke
Cats living in a smoker’s household are three times more likely to develop lymphoma. Compared to living in a smoke-free environment, cats exposed to secondhand smoke also have a greater chance of developing squamous cell carcinoma or mouth cancer. Cancer is also developed mostly due to the cat's grooming habits. As cats lick themselves while they groom, they increase chances of taking in the toxic, cancer-causing carcinogens that gather on their fur, which are then exposed to their mucus membranes.
Lifestyle
Providing a cat with the healthiest lifestyle possible is the key to prevention. Decreasing the amount of toxins, including household cleaning products, providing fresh and whole foods, clean and purified water, and reducing the amount of indoor pollution can help cats live a longer and healthier life. To lessen susceptibility to diseases, domesticated cats should be kept inside the household for most of their lives to reduce the risk of interacting with other stray cats that could be infected with diseases.
Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI tract) and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The symptoms relate to the organ affected and can include obstruction (leading to difficulty swallowing or defecating), abnormal bleeding or other associated problems. The diagnosis often requires endoscopy, followed by biopsy of suspicious tissue. The treatment depends on the location of the tumor, as well as the type of cancer cell and whether it has invaded other tissues or spread elsewhere. These factors also determine the prognosis.
Overall, the GI tract and the accessory organs of digestion (pancreas, liver, gall bladder) are responsible for more cancers and more deaths from cancer than any other system in the body. There is significant geographic variation in the rates of different gastrointestinal cancers.
Nasopharyngeal carcinoma (NPC) is caused by a combination of factors: viral, environmental influences, and heredity. The viral influence is associated with infection with Epstein-Barr virus (EBV). The Epstein-Barr virus is one of the most common viruses. 95 percent of all people in the U.S. are exposed to this virus by the time they are 30–40 years old. The World Health Organization does not have set preventative measures for this virus because it is so easily spread and is worldwide. Very rarely does Epstein-Barr virus lead to cancer, which suggests a variety of influencing factors. Other likely causes include genetic susceptibility, consumption of food (in particular salted fish) containing carcinogenic volatile nitrosamines. Various mutations that activate NF-κB signalling have been reported in almost half of NPC cases investigated.
The association between Epstein-Barr virus and nasopharyngeal carcinoma is unequivocal in World Health Organization (WHO) types II and III tumors but less well-established for WHO type I (WHO-I) NPC, where preliminary evaluation has suggested that human papillomavirus HPV may be associated. EBV DNA was detectable in the blood plasma samples of 96% of patients with non-keratinizing NPC, compared with only 7% in controls. The detection of nuclear antigen associated with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV can infect epithelial cells and is associated with their transformation. The cause of NPC (particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play an important role. More importantly, EBV DNA levels appear to correlate with treatment response and may predict disease recurrence, suggesting that they may be an independent indicator of prognosis. The mechanism by which EBV alters nasopharyngeal cells is being elucidated to provide a rational therapeutic target.
Treatment options vary and depend on the type and stage of cancer. Common treatments include surgery, chemotherapy, radiation therapy, amputation, and immunotherapy. A combination of therapies may be used. Knowledge and treatment of cancer have increased significantly in the past three decades. Survival rates have also increased due to the increase prevalence of canine cancer treatment centers and breakthroughs in targeted drug development. Canine cancer treatment has become an accepted clinical practice and access to treatment for owners has widely expanded recently. Cancer-targeting drugs most commonly function to inhibit excessive cell proliferation by attacking the replicating cells. However, there is still a prevalent pharmacy gap in veterinary oncology.
There is one canine tumor vaccine approved by the USDA, for preventing canine melanoma. The Oncept vaccine activates T-cell responses and antibodies against tumor-specific tyrosinase proteins. There is limited information about canine tumor antigens, which is the reason for the lack of tumor-specific vaccines and immunotherapy treatment plans for dogs.
Success of treatment depends on the form and extent of the cancer and the aggressiveness of the therapy. Early detection offers the best chance for successful treatment. The heterogeneity of tumors makes drug development increasingly complex, especially as new causes are discovered. No cure for cancer in canines exist.
Some dog owners opt for no treatment of the cancer at all, in which case palliative care, including pain relief, may be offered. Regardless of how treatment proceeds following a diagnosis, the quality of life of the pet is an important consideration. In cases where the cancer is not curable, there are still many things which can be done to alleviate the dog's pain. Good nutrition and care from the dog's owner can greatly enhance quality of life.