ORAL CANCER AND ITS EPIDEMIOLOGY, THERAPY AND RISK FACTORS, CASE STUDIES IN KARNATAKA: A REVIEW
HTML Full TextORAL CANCER AND ITS EPIDEMIOLOGY, THERAPY AND RISK FACTORS, CASE STUDIES IN KARNATAKA: A REVIEW
Poojitha B. Sridhara, S. Chandrashekar, Chandan Shivamallu, Kollur Shiva Prasad, D. Chandan, Sharanagouda S. Patil and S. M. Gopinath *
Department of Biotechnology, Davangere University, Shivagangotri, Davangere, Karnataka India.
ABSTRACT: Oral cancer is one of the lethal cancers, having first rank in India and sixth most deadly cancer in world and most of the time occurs due to improper lifestyle and adverse habits. Cancers of the lung, oral cavity, pharynx, larynx, esophagus, urinary bladder, renal, pelvic and pancreas are among the neoplastic diseases induced by smoking. Epidemiological studies have firmly identified the connection between smoking and oral cancer. In the review, we have discussed about the risk factor of oral cancer, recent advancement in treatment of oral cancer and cases in Karnataka state of India. We focused on the reason of oral cancer, as many studies suggested that tobacco (smokeless and smoking), excessive consumption of alcohol, and exposure of radiation are the main causing agents of oral cancer. People adopted tobacco socially in India and there is something to worry about that people are not aware that tobacco is primary causal factor of oral cancer. In present study, we focused on the treatment of oral cancer and what modification in DNA can lead the oral cancer and how to reverse the action of the cancerous cells to prevent the cancer.
Keywords: Oral cancer, ICMR, Karnataka, Smokeless tobacco, Alcohol consumption, Chemotherapy, Chemoradiotherapy
INTRODUCTION: Oral cancer has been attributed to being one of the most challenging and relevant form of cancer incidences. Despite enhanced prognosis and progress in therapy and research, the survival of Oral Cancer patients has still not significantly improved. Thus, this poses a severe challenge for the research related to biomedical sciences.
This paper targets to cover vital aspects of this particular cancer, underlying, histological, clinical, and molecular notes for a clearer picture of their biological framework. This would thus allow researchers to create a blueprint that could assist in bettering the patients with a superior prognosis. According to some research approximately two lakh people deceased yearly worldwide and about 46 thousand die in India by oral cancer 1. Some studies suggest a significant difference in the rate of mouth cancer in various areas of the world.
Oral cancer is the sixth most common cancer in the world. In Southeast Asia, oral cancer is the second most common cancer and second common cause of cancer death among males.
One‑third case of global oral cancer and one‑half of global mortality from oral cancer are described from Southeast Asia. Persons exposed to smoking, drinking, and betel quid chewing together are at high risk compared to individuals exposed to any one of these factors 2. In Southeast Asia, most cases of OSCC happen in the buccal and esophagus areas of the oral cavity 3. Oral cancer is considered one of the major health issues in the entire Indian subcontinent and is ranked third among the all kinds of cancer in the country.
Around 20 per 100,000 population, one that accounts for about 30% of all cancers in India are patients suffering from oral cancer 4, 5. The incidence difference of the disease and the pattern can be attributed to the demography of the region, along with prevalence difference in the regions because of disease-specific risk features 6. It is one of the highest concerning diseases in the country. First of all, later-stage diagnosis, resulting in poor treatment and cost burden to the patients below the poverty line 7. Moreover, there is limited health service in middle- and low-income countries and to trained providers 8. Earlier detection bids the best chance for a better and longer survival rate and improves treatment results and affordable healthcare 9. Thirdly, people of lower socioeconomic groups affected more by oral cancer because of more introduction to risk factors like tobacco, betel nut, etc 10. Lastly, the common cases presented to a healthcare center are way at advanced stages of cancer, and the chances of survival are minimum by then 11. Profound knowledge on the matter, aetiology and risk factors are the ways to curb the growth of oral cancer.
- Definition and Illustrations: Oral cancer is a neoplasia of the malignant nature, one that arises on the oral cavity or the lip. Oral cancer is predominantly known as squamous cell carcinoma (OSCC). This is because around the dental area, almost 90% of the cancers originate histologically in the squamous cell lining 12, 13. There are various stages of differentiation, along with a tendency to metastasize into the lymph node 14. The occurrence of OSCCs differs in various parts of the world and it is noticed that exposure to risk factor is also differ 15. A quantitative study of any disease depends on specific and constant definitions. This also stands true for cancer epidemiology, which includes explanations of topography, histo-pathology and tumour performance. In case of oral cancer, variations prevail in the anatomical subsites involved in both oral cavity and oropharynx groupings. Therefore, oral cancer is progressively being recognized as part of two different diseases: oral cavity cancer (OCC), also known as ‘mouth cancer’ and oropharyngeal cancer (OPP), also known as ‘throat cancer’.
Incidence rates the best measure the incidence (risk) burden of cancer in a population. Cancer incidence rates are the number of new cases diagnosed in the population over a given period (usually a year) expressed as a rate by dividing this by the total population at risk during that period (denominator). The denominator is usually adjusted to account for different age profiles in different populations referenced to a standard population, which has a known population age-structure – this is often the European Standard Population, which is a theoretical population adding up to a total of 100,000 persons.
Given the relatively low volume of oral cancer and the long lag-time between exposure to risk factors and cancer diagnosis, case-control study designs are the mainstay of epidemiological investigations. In such case-control studies, a group of patients with oral cancer (‘cases’) and a comparable group of study participants without oral cancer (‘controls’) are recruited. Information on their histories of exposure to risk factors is collected and compared. The epidemiology of the cancer sheds light into an interesting fact that among ethnic groups, this cancer is prevalent more in men than in women [http://seer.cancer.gov/statfacts/html/oral cav.html]. In worldwide reports, cancers of all regions of the oral cavity and pharynx are grouped and collectively represent the sixth most common cancer in the world.
The most common symptoms of oral cancer are as follows: it is seen in an oral cancer patient that they have swellings or thickenings, lumps, crusts on the lips and gums inside the mouth. Even the texture of teeth changes due to oral cancer. Sometimes red or white patches develop inside the mouth, and they bleed. The oral cancer causes loss of feeling or numbness but sometimes it is also seen that it pains in the area of mouth. While some patients feel persistent sores on the neck and mouth that bleed, and the wounds do not heal quickly. Even a sore throat becomes chronic which results in hoarseness and a change in voice. Oral cancer patients have difficulty swallowing and chewing, speaking, and moving the jaw and tongue. Ear pain and dramatic weight loss are also symptoms of oral cancer.
- Causing Agents: Oral cancer is noticed different part of the oral cavity like lips, tongue, salivary glands, soft palate and oropharynx. Multiple studies suggest that oral cancer-causing agents contain dietary factors, smokeless tobacco chewing (Gutka, Pan etc.), tobacco smoking (Beedi, Cigarette etc), alcohol drinking, Human Papilloma Virus (HPV) infections and exposure to carcinogenic agents 16. Oral cancer is the most common cancer in India amongst men (16.1% of all cancers) and second most common cancer in amongst women (10.4% of all cancer). According to a survey, due to tobacco use, mortality is estimated at upwards of 3.5 thousand persons per day. The “India Against Cancer”works against cancer in India, which is run under the doctors and researchers at the National Institute of Cancer Prevention and Research (NICPR), a premier institute under the Indian Council of Medical Research (ICMR).
According to “India Against Cancer”, due to tobacco (smoked and smokeless), approximately 3,17,928 deaths (men and women) were recorded in 2018 in India. It is reported (Consolidated report of hospital-based cancer registries 2007-2011, National Cancer Registry Programme (ICMR), Bangalore) that tobacco contribute in oral cancer about 80-90% of all cancer.
Vishma et al., reported in her studies that she collected 479 sample of oral cancer from Mandaya, Karnataka17. She reported that 36.7% of the total oral patients supposed that oral cancer can be prevented by treatment, 41.8% believed that it can be treated, 35.1% of the patients supposed that oral cancer is increased with the age, while 18.6% patients think that oral cancer is infectious. In the similar study conducted in Gorakhpur, Uttar Pradesh18 it is noticed that 74.1% of the total patients said that oral cancer is curable, 40.9% did not agreed with risk for oral cancer increases with the age, where 10.8% believed that oral cancer is infectious.
Survey was conducted in rural Bangalore and mentioned in his paper that only 19.28% of the total patients thought that oral cancer is preventable 19.
The most common symptoms are ulcer and lump in the mouth mentioned that in their studies that 40% of the total (479) respondents did not know the oral cancer’s symptoms. In different studies conducted in Gorakhpur (40%), Portugal (10%), Chennai (31.7%), and Turkey (20.8%) of the patients did not know about the common symptoms of oral cancer. Only 8.1% of the responders believed that smokeless tobacco is the causing agent, only 0.8% of the total responders thought that smoking is the factor for oral cancer, while 43% of the responders knew that more than three (chewing of tobacco, smoking and alcohol consumption, etc.) causing agents of oral cancer. A study suggested that around 90% of the total responders believed that smokeless tobacco is a risk factor of oral cancer and 75.4% patients believed that smoking is risk factors for oral cancer. According to monteiro 20, 21, 22 studies that 89.5% of the responders believed that tobacco (89.5%) is risk factor for oral cancer and 32.3% responders said that alcohol is risk factor for oral cancer.
Sathyanarayana et al., 23 found that with regard to risk factors, 50% of the respondents knew that cigarette smoking was a risk factor for oral cancer. Other Risk factors for the growth of oral cancer includes, smoked tobacco (cigarette, cigar, and pipe) people have 6 times more cancer than the non-smoker people. Smokeless tobacco (snuff, dip, and chewing tobacco) users are 50 times more likely to develop cancers of the cheek, gums and lining of the lips. Excessive consumption of alcohol is also a high-risk factor of oral cancer which causes 6 time more in drinker then non-drinker. It is also reported that who has family history of oral cancer, is at high risk of cancer. The human papillomavirus (HPV) also causes oral cancer. To avoid oral cancer, self-examination should be conducted at least once in a month. If any lumps are presented in the area of the mouth, then should consult with a dentist. The American Cancer Society mentioned oral cancer screening tests should be done in every 3 years who over age 20 and annually for those who over age 40.
- Tobacco: In the year 2007, IARC decided “there is quite an evidence to establish that snuff smoke is carcinogenic, and for example, it causes cancer of the oral cavity and pancreas” (World Health Organization, 2007) 24. Risk for oral cancer is 3 times more in smokers as compared to nonsmokers 25. Immunity weakens in case of Cigarette smoking in the oral cavity because of the risk of periodontitis, gingivitis, oral cancer 26. It contains various elements enhancing cancer that are mostly: nitrosamines, benzopyrenes, and aromatic amines. Such chemicals are termed pre-carcinogens that must go through coordinated alterations triggered by oxidative enzymes. The final product thus becomes depleted of electrons to be covalently bound to the DNA. This generates an adduct mutated area, free radicals, with unpaired electrons make them reactive and are being capable of enhancing mutations by complex mechanisms 27.
India is known as a global capital for smokeless tobacco because, according to the Global Adult Tobacco Survey- 2010, smokeless tobacco is consumed by more than one-third (35%) adult population in India. Therefore, it is a common community health problem in India. Out of 35% population, 21% are used only smokeless tobacco products, while 9% are used only smoking, and 5% adult population are addicted to both smokeless and smoking tobacco products (GATS India 2009-2010) 28. 20.6% of the adult population is addicted in the United States of America. In western countries, smokeless tobacco use is similar to India. According to World Health Organization, tobacco use is high risk factor for oral cancer which is responsible for 22% of cancer death in over the world. According to the International Agency for research on cancer (IARC), smokeless tobacco is associated with oral cancer only. Gajalakshmi et al., 29 reported in his paper that due to oral cancer, the death rate has increased by 5times in smokeless tobacco users than non-tobacco users. The larynx, pharynx, esophagus, cervix, and stomach were also found among the smokeless tobacco users.
- Alcohol: Alcohol is both considered a local and systemic risk factor. This is seen as augmented permeability of mucosa in the oral region, epithelial lipid dissolving that causes epithelial atrophy and DNA synthesis interference. It also has genotoxicity and mutagenic effects that cause low salivary flow. It affects the ability of the liver to deal with carcinogenic compounds. Their chronic use is associated with damage of immunity that results in increased probability of infections and neoplasms 30.
- Other Factors: Human papillomavirus is mainly linked with the carcinoma of the oropharynx 31 along with ultraviolet radiation (UV). HPV18 is a possible cause of oral cancer 32. HPV-related head and neck squamous cell carcinoma (HNSCC) common sites are tonsils and the base of the tongue inside the oropharynx. The presence of HPV is an established prognostic biomarker of favorable outcome in locally advanced oropharyngeal cancers 33. HPV contributes to carcinogenesis with the help of two virus-encoded proteins: E6 protein p53 tumor suppressor gene degradation; E7 tumor suppressor gene pRb degradation (retinoblastoma protein) 34, leading to an inhibitor overexpression of cyclin-dependent kinase. UVB also causes `lip cancer.
- Tumor Microenvironment (TME): The Tumor Microenvironment (TME) of OSCC includes immune cells, cancer-associated fibroblasts (CAFs). Oncogenic changes regarding gene expressions lead to microenvironmental changes such as overproduction of cytokines, ROS accumulation, epithelial-mesenchymal transition.
The immune response in OSCC is suppressed by induced apoptosis by T cells, overexpression of cytokines, and alterations in antigen processing machinery 35. Transforming growth factor-β (TGF-β) offers to EMT and immunosuppression, along with the evolution of CAFs. OSCC uses the glycolytic and oxidative metabolism to feed tumor genesis through mechanisms which are coupled between regions of cancer cell (parenchyma) and TME cells (stroma) 36.
- Case in Karnataka: Reasons for Late Diagnosis: A study on oral cancer was conducted based on hospital records by Karnataka Cancer Treatment and Research Centre (KCTRI), Karnataka, India Priyadarshini selected 1113 oral cancer patients, who were registered in hospital between January, 2001 to December, 2005 for the treatment for oral cancer 37. This study suggested that North Karnataka people did not become aware of the reason for oral cancer. The study was done on the basis of socio-economic status of oral cancer patients, she selected from three different regions of Karnataka-rural, urban and semi-urban. Almost 98% of the patients used tobacco, betel nut etc., which habit tobacco chewing habit was significantly higher (p<0.001) compared to other habits of patients. Approximately 33.5% of the patients were suffered from buccal mucosa carcinoma and 28.5% of the patients were suffered with tongue carcinoma. It is also reported in some literature that tongue carcinoma was most common site for oral cancer after the buccal mucosa carcinoma 38, 39, 40.
De Vita discussed the reason for oral cancer; tobacco, alcohol, and radiation exposure are the most general risk factor for the occurrence of oral cancer 41. Prolonged oral cancer can cause death 42, 43. The cancer patients in South Karnataka based on their type of cancer, patient’s age, lifestyles, and diabetes. It is reported that glucose inhibits DNA synthesis in cultured hepatocytes, a prerequisite for cellular proliferation 44. Hence diabetics should show a certain amount of immunity against cellular proliferative diseases like cancer 45, 46.
The Kasturba Medical Hospital, Mangalore, Karnataka treats cancer patients since the year 1999. Itagappa et al., 47 chose Kasturba Medical Hospital and took 400 cancer patients for his studies. 25.5% patients out of 400 cancer patients were observed with oral cancer, shown in Table 1. Ghose et al., 48 reported that tobacco is the primary causal agent for oral cancer in Indian subcontinent. Itagappa et al., reported that 28.4% of the total oral cancer patients were addicted to tobacco, and 64.7% of patients did not have addiction to alcohol, while only 6.9% of the total patients did not have any addiction history, shown in Table 2. In the ICMR report written by Ramachandran et al., 48% of male oral cancer patients and 20% of female oral cancer patients were addicted to tobacco in India 49. However, these reports indicate that oral cancer is higher in both sexes (male and female) than the other type of cancer. Excessive use of tobacco is a known primary causing agent for oral cancer in South Karnataka, India. Mukherjee et al. reported that tobacco products (Pan and gutka, etc.) chewing is a socially accepted practice among both sexes (male and female) in many regions of India 50.
TABLE 1: TYPE OF TUMOUR DISTRIBUTION AND SEGREGATION OF DIABETICS AND NON-DIABETICS
S. no. | Tumour | No of cases (n) | % of cases | Diabetic cases | Non-Diabetic cases |
1 | Oral | 102 | 25.5 | 2.0 | 100 |
2 | Breast | 73 | 18.2 | 1.0 | 72 |
3 | Cervix | 73 | 18.2 | 3.0 | 70 |
4 | Non- Hodgkins Lymphoma | 25 | 6.2 | - | 25 |
5 | Oesophagus | 24 | 6.0 | - | 24 |
6 | Ovary | 19 | 4.7 | 2.0 | 17 |
7 | Lung | 11 | 2.7 | - | 11 |
8 | Leukemia | 10 | 2.5 | - | 10 |
9 | Brain | 9 | 2.3 | - | 09 |
10 | Parotid | 8 | 2.0 | 1.0 | 07 |
11 | G.I.T. | 8 | 2.0 | 1.0 | 08 |
12 | Uterine | 7 | 1.7 | - | 06 |
13 | Multiple Myeloma | 6 | 1.5 | - | 06 |
14 | Liver | 5 | 1.3 | - | 05 |
15 | Thyroid | 5 | 1.3 | - | 05 |
16 | Kidney | 4 | 1.0 | - | 04 |
17 | Lymphoma | 3 | 0.8 | - | 03 |
18 | Prostate | 3 | 0.8 | - | 03 |
19 | Bladder | 2 | 0.5 | - | 02 |
20 | Vagina | 2 | 0.5 | - | 02 |
21 | Testis | 1 | 0.3 | - | 01 |
Total | 400 | 100 | 10 | 390 |
Note: This table has been adopted from the Itagappa and Rao, 2004.
TABLE 2: DISTRIBUTION % OF TUMOUR CASES AS PER PATIENTS’ ADDICTIVE HABITS
S. no. | Tumour | Tobacco user | Tobacco and alcohol user | No addiction |
1 | Oral | 64.7 | 28.4 | 6.9 |
2 | Breast | 26 | - | 74.0 |
3 | Cervix | 38.4 | - | 61.6 |
4 | Non- Hodgkins Lymphoma | 32 | 8 | 60 |
5 | Oesophagus | 41.7 | 45.8 | 12.5 |
6 | Ovary | 21.1 | - | 78.9 |
7 | Lung | 27.3 | 63.6 | 9.1 |
8 | Leukemia | 10 | - | 90 |
9 | Brain | 22.2 | 11 | 66.7 |
10 | Parotid | 37.5 | 50 | 12.5 |
11 | G.I.T. | - | 50 | 50 |
12 | Uterine | 14.3 | - | 85.7 |
13 | Multiple Myeloma | 16.7 | 50 | 33.3 |
14 | Liver | - | 60 | 40 |
15 | Thyroid | - | 20 | 80 |
16 | Kidney | 25 | 25 | 50 |
17 | Lymphoma | 66.7 | - | 33.3 |
18 | Prostate | 33.3 | 66.7 | - |
19 | Bladder | 50 | 50 | - |
20 | Vagina | 100 | - | - |
21 | Testis | - | - | 100 |
Total | 400 | 100 | 10 |
Note: No patients were found with alcohol addiction
There is a wide variable rate in the incidence of oral cancers in India; she recorded that oral cancer was established in all cancers, approximately 12% in men and around 8% in women. In oral cancer, the rate of survival is very less approximately 50%. But early diagnosis of oral cancer rises the chances of patient’s survival. Mouth is easily accessible for medical examination and self-examination.
Lack of information about the causes of oral cancer, their signs, and symptoms among the population are the common reasons for diagnosis at an advanced level. Moreover, if the patients know the risk factor for oral cancer, then it could be preventable or controllable 51. Gopinath noticed that rural people have not enough knowledge about oral cancer and its causes and preventions compared to urban people 52. This data was taken by Gopinath and his colleagues, as he collected data from the rural area of Dakshina Kannada district of Karnataka in October 2014 with the help of a questionnaire. In that survey, they took data of 267 people with the age group 12-80 years who came looking for dental treatment at Nitte University, Karnataka 53.
According to Gopinath, 13.1% people out of 267 people did not hear about the oral cancer, 4.9% people believed that oral cancer caused by hereditary, and some people believed it spreads by sexual and blood transfusion. While 6.7% of people said that sharing clothes and utensils are a major reason for oral cancer. Ramachandra also explained in his article that illiteracy is a common cause for increasing oral cancer incidences along with chewing habits. Rural patients were also confused with the question regarding oral cancer in AIDS patients 54. 3.4% of patients believed that most oral cancer is seen in HIV-positive patients. Argerak is expressed concern about psychosocial thoughts for the post-treatment of head and neck cancer patients. Ariyawardana's survey revealed that 5.9% of the population was not aware of treatment possibilities, and 5.4% believed that there is no treatment available for oral cancer 55. This may lead to a “loss of hope” type of situation, resulting in a delay in seeking treatment, or the patient may not seek treatment. Das expressed concern in his article about increase the awareness for health education and cancer prevention 56.
8. Recent Advances in Oral Cancer:
8.1 Chemotherapy: Chemotherapeutic agents or radioactive drugs are used in the treatment of oral and other cancers. Chemotherapy and immune therapy drugs play an important role in the treatment of oral cancer. Chemotherapy is used in the primary treatment of oral cancer and in combination with radiotherapy. Extension of survival is possible with only chemotherapy protocols. Survival rates of 30–60% at three to five years are now being reported. Patient selection for these intense treatment regimens must take careful consideration of the patient’s overall clinical status 57. Treatment by highly skilled physicians with multidisciplinary radiotherapy, medical, surgical, nursing and other supportive care is desired to tolerate these patients through such intense treatment protocols 58. Chemotherapy is considered especially for those patients who are ineligible for surgery. It is determined that associated targeted agents with radiotherapy combinations cause lower treatment-related toxicity, have low operating curability rates, or harbour tumours for which non-surgical therapy represents a more acceptable treatment. While adjuvant chemotherapy has not been significant used in the treatment of oral cancer patients after surgery. There is no evidence of the benefit of chemotherapy in the treatment of head and neck cancer.
8.2 New Approach in Chemotherapy: New chemotherapeutic drugs have been developed that may be more effective for the treatment of oral cancer. Intra-arterial chemotherapy has been examined in combination with radiation therapy for improving its effectiveness, in which drugs are injected directly into the bloodstream. Another new approach is introduced intra-lesional chemotherapy for head and neck cancers treatment, in which chemotherapy drugs are injected directly into the tumor. But, it has side effects that these drugs are tended to the nearby tissues and rest of the body. Therefore, its use is limited for treatment. To reduce the side effects of chemotherapy drugs, researches made a drug solution so that it can be made localized treatment.
8.3 Chemoradiotherapy: Chemoradiotherapy is the study of chemotherapy with the combination of radiation. In this process, chemotherapy acted as a radiation sensitizer and is used to reduce radiation resistance. Studies suggested that chemoradio-therapy is a better approach than radiotherapy alone in cancer patients, but it has a great risk of reappearance of cancer. In the European Organization for Research and Treatment of Cancer (EORTC), 334 patients were tested with either cisplatin 100mg/m2 with radiation and radiation alone at same time interval (day 1, day 22, and day 43) 59, 60. The same experiments were carried in Radiation Therapy Oncology Group (RTOG), which treated 459 patients 61, 62. Unfortunately, they came to different conclusions about the advantage of chemoradiation. Based on investigation of these two studies, adjuvant chemoradiation gave better results than only radiation. Therefore, chemo-radiotherapy can be applied on oral cancer patients. Radiotherapy is a local treatment in oral cancer and local control plays an important role in getting cure from cancer suppression 63, 64, 65. While metho-trexate (anti-metabolites) is commonly used for palliative chemotherapy, platinum chemotherapy is also most active drug compound for the treatment of head and neck cancer, however the survival time rate of cancer patients, is exceeded rarely six months 66. According to Leon 67, survival time is fallen to approximately three months in patients who had treated failed platinum-based therapies.
However, radiation has side effects. Chemotherapy is a systemic treatment that goes via bloodstream throughout the body and chemoradiotherapy is a localized treatment that is worked at a specific site. Therefore, radiation side effects have been seen in cancer patients at the part of body where radiation therapy is being given. While most cancer patients do not feel side effects like nausea or vomiting if stomach is not the part of the treatment (there are many medicines that are used to minimize the side effects of the radiation) and similarly hair loss is seen in the cancer patient which has been gone to treatment of head. Because of radiation therapy is area specific treatment; therefore, side effects also see at the area which has been undergone the treatment. For example, if male patients undergo radiotherapy in oral cancer, then he will loss teeth and bread hair permanently.
While some cancer patients feel fatigued during radiation therapy. Skin irritation and mucositis are most common side effects and get worse with time as treatment carries on. However, after treatment, the body starts to repair this harm, salivary begin functional.
8.4 Other Approaches:
8.4.1 DNA Changes in Oral Cancer: It is still an unknown factor what DNA modifications are responsible for causing cells of the oral cavity and oropharynx to become cancerous. Mutation in the p53 gene of the oral cavity is responsible for oral cancer. The protein product of the p53 gene commonly works to prevent cells from growing too much and helps to destroy cells with DNA damage too extensive for the cells to repair. The p53 DNA damage can lead to the overgrowth of abnormal cells and the formation of cancers. Multiple studies suggest that detection of the p53 gene can allow detecting cancer at a very early stage that can be treated at a time. These tests also provide margin to the doctors for checking that all cancer cells can be removed or not. Another DNA change was found in oral cancers, in which DNA of human papillomavirus (HPV) mixes together with the patient’s own DNA.
8.4.2 Gene Therapy: Gene therapy is being used in cancer studies. In gene therapy, it is determined that how can be reversed DNA changes in oral cancer. Therefore, the results of the DNA changes can be stopped to become cancerous.
8.4.3 Tumour Growth Factors: Studies suggested that growth factors (hormone-like substances) promote cell growth in the body. The growth factor attaches to growth factor receptors to activate the cell for unlimited growth. One of the growth factors that have been linked to oral and oropharyngeal cancers is called epidermal growth factor (EGF). Oral and oropharyngeal cancers with too many EGF receptors tend to be especially aggressive 68.
8.4.4 Vaccines: Most people think of vaccines as a way to prevent infectious diseases such as polio or measles. However, vaccines are being studied as a way to treat people with cancer by helping their immune to recognize and attack the cancer cells. Since some oral and oropharyngeal cancers contain DNA from human papillomaviruses, vaccines against these viruses are being studied as a treatment for these cancers. Biological treatment alone and with radiotherapy can be a good approach for treatment than the other approaches. Researchers need to focus on targeted agents, such as the EGFR inhibitors and the VEGF inhibitor bevacizumab, which have added a new dimension to potential treatment 69.
CONCLUSION: Oral cancer is deadly cancer as it has the first rank in the Indian subcontinent. But still, there is no proper treatment and early-stage diagnosis. The most appropriate treatment is chemoradiotherapy. Intra-arterial and intra-letional chemoradiotherapy are new approaches for the treatment of oral cancer. Government should run an awareness program to the citizens. As many surveys suggested that people are no aware of the reason for oral cancer, and it can be preventable or not. They even do not know that it could be genetic. If oral cancer detects at an early stage, then it could be treated successfully. Therefore, it becomes a necessity to develop the method for early detection of oral cancer. As we also know oral cancer can be examined by self. So that it is compulsory that every person should to examine oral cancer once in a month.
ACKNOWLEDGEMENT: We would like to acknowledge Davangere University, JSS Academy of Higher Education & Research, Amrita School of Arts and Sciences, and National Institute of Veterinary Epidemiology and Disease Informatics for the infrastructure support.
CONFLICTS OF INTEREST: The author has no conflicts of interest in the present review
REFERENCES:
- Coelho KR: Challenges of the oral cancer burden in India. Journal of cancer epidemiology 2012; 17.
- Zeng J, Tang Y, Wu P, Fang X, Wang W, Fan Y, Li X and Zhao S: Alcohol consumption, tobacco smoking, betel quid chewing and oral health associations with hypopharyngeal cancer among men in Central South China: a case–control study. Cancer Management and Research 2019; 11: 6353.
- Kumar M, Nanavati R, Modi TG and Dobariya C: Oral cancer: Etiology and risk factors: A review. Journal of Cancer Research and Therapeutics 2016; 12(2): 458.
- Varshitha A: Prevalence of oral cancer in India. Journal of Pharmaceutical Sciences and Research 2015; 7(10): 845.
- Sharma S, Satyanarayana L, Asthana S, Shivalingesh KK, Goutham BS and Ramachandra S: Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. Journal of Oral and Maxillofacial Pathology: JOMFP 2018; 22(1): 18.
- Manoharan N, Tyagi BB and Raina V: Cancer incidences in rural Delhi-2004-05. Asian Pacific Journal Cancer Prevention 2010; 11: 73-7.
- Khandekar SP, Bagdey PS and Tiwari RR: Oral cancer and some epidemiological factors: A hospital-based study. Indian J Community Med 2006; 31: 157-9.
- Kumar S, Heller RF, Pandey U, Tewari V, Bala N and Oanh KT: Delay in presentation of oral cancer: A multifactor analytical study. Nat Med J Ind 2001; 14: 13-7.
- Fritz: International Classification of Diseases for Oncology. World Health Organization Geneva, Switzerland 2000; 3.
- Conway DI, Petticrew M, Marlborough H, BerthillerJ, Hashibe M and Macpherson LMD: Socioeconomic inequalities and oral cancer risk: a systematic review and meta-analysis of case-control studies. International Journal of Cancer 2008; 122(12): 2811-19.
- Allgar VL and Neal RD: Sociodemographic factors and delays in the diagnosis of six cancers: analysis of data from the National Survey of NHS Patients: cancer the British Journal of Cancer 2005; 1971-75.
- Vigneswaran N and Williams MD: Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral and Maxillofacial Surgery Clinics 2014; 26(2): 123-41.
- Lambert R, Sauvaget C, de Camargo-Cancela M and Sankaranarayanan R: Epidemiology of cancer from the oral cavity and oropharynx. European Journal of Gastroenterology & Hepatology 2011; 23(8): 633-41.
- Wong SY and Hynes RO: Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 2006; 5(8): 812-7.
- Yan L, Chen F, Liu F, Qiu Y, Wang J, Wu J, Bao X, Hu Z, Peng X, Lin X and Cai L: Differences in modifiable factors of oral squamous cell carcinoma in the upper and lower of oral fissure. Oncotarget 2017; 8(43): 75094.
- Niaz K, Maqbool F, Khan F, Bahadar H, Hassan FI and Abdollahi M: Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiology and Health 2017; 39.
- Shashikantha SK: Awareness of oral cancer and its risk factors in a rural community in Mandya, Karnataka, India. International Journal of Community Medicine and Public Health 2016; 3(1): 347.
- Mangalath U, Aslam SA, Khadar AH, Francis PG, Mikacha MS and Kalathingal JH: Recent trends in prevention of oral cancer. Journal of International Society of Preventive & Community Dentistry 2014; 4(S3): S131.
- Shah SP and Praveen BN: Awareness of oral cancer in rural Bangalore population: A questionnaire-based study. International Journal of Scientific Study 2014; 1(6): 14-6.
- Agrawal M, Pandey S, Jain S and Maitin S: Oral cancer awareness of the general public in Gorakhpur city, India. Asian Pacific J of Cancer Preventi 2012; 13(10): 5195-9.
- Yadav D, Tarar S, Ghosh N, Tiwari RP, Bisen PS and Prasad GB: Incidence of Metabolic Syndrome and Diabetes Mellitus in Raipur City of Chattishgarh State-A Preliminary Study. Indian Journal of Public Health Research & Development 2013; 4(3): 58.
- Hatsukami DK, Ebbert JO, Feuer RM, Stepanov I and Hecht SS: Changing smokeless tobacco products: new tobacco-delivery systems. American Journal of Preventive Medicine 2007; 33(6): S368-78.
- Odukoya OO, Sekoni AO, Onajole AT and Upadhyay RP: Alcohol consumption and cigarette smoking pattern among brothel based female sex workers in two local government areas in Lagos state, Nigeria. African Health Sciences 2013; 13(2): 490-7.
- Lee PN and Hamling J: Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Medicine 2009; 7(1): 1-47.
- Gillison ML: Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck 2007; 29(8): 779-92.
- Phaniendra A, Jestadi DB and Periyasamy L: Free radicals: properties, sources, targets, and their implication in various diseases. Indian Journal of Clinical Biochemistry 2015; 30(1): 11-26.
- Bhattacharyya H, Pala S, Medhi GK, Sarkar A and Roy D: Tobacco: Consumption pattern and risk factors in selected areas of Shillong, Meghalaya. Journal of Family Medicine and Primary Care 2018; 7(6): 1406.
- Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J and Sankaranarayanan R: Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases. Oral Oncology 2008; 44(5): 446-54.
- El–Serag HB and Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132(7): 2557-76.
- Reidy J, McHugh E and Stassen LF: A review of the relationship between alcohol and oral cancer. Surgeon 2011; 9: 278-83.
- Dalianis T: Human papillomavirus and oropharyngeal cancer, the epidemics, and significance of additional clinical biomarkers for prediction of response to therapy (Review). Int J Oncol 2014; 44: 1799-1805.
- [http://monographs.iarc.fr/ENG/Classification/index.php].
- Kang H, Kiess A and Chung CH: Emerging biomarkers in head and neck cancer in the era of genomics. Nat Rev Clin Oncol 2015; 12: 11-26.
- Neville, Brad W, Douglas D, Damm, Carl M, Allen and Angela C: Chi: Oral and maxillofacial pathology. Elsevier Health Sciences 2015.
- Cavallo F, De Giovanni C, Nanni P, Forni G and Lollini PL: The immune hallmarks of cancer. Cancer Immunol Immunother 2011; 60: 319-26.
- Wendt MK, Allington TM and Schiemann WP: Mechanisms of the epithelial–mesenchymal transition by TGF-β. Future Oncology 2009; 5(8): 1145-68.
- Aruna DS, Prasad KV, Shavi GR, Ariga J, Rajesh G and Krishna M: Retrospective study on risk habits among oral cancer patients in Karnataka Cancer Therapy and Research Institute, Hubli, India. Asian Pac J Cancer Prev 2011; 12(6): 1561-6.
- Arifulla KM, Saeed MY, AM P, Vivekanand PH, Patil R, Qadir R and Shafi N: Study of oral squamous cell carcinoma in hospital based patients, Bijapur, Karnataka. International Journal of Current Medical and Applied Sciences. 2014; 3(2).
- Niaz K, Maqbool F, Khan F, Bahadar H, Hassan FI and Abdollahi M: Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiology and Health 2017; 39.
- Dhanuthai K, Rojanawatsirivej S, Thosaporn W, Kintarak S, Subarnbhesaj A, Darling M, Kryshtalskyj E, Chiang CP, Shin HI, Choi SY and Lee SS: Oral cancer: A multicenter study. Medicina Oral, Patologia Oral y Cirugiabucal 2018; 23(1): e23.
- Dhanuthai K, Rojanawatsirivej S, Subarnbhesaj A, Thosaporn W and Kintarak S: A multicenter study of oral malignant tumors from Thailand. J Oral Maxillofac Pathol 2016; 20: 462-6.
- Kademani D, Baltlai E, Lewis J and Keller E: Analysis of death certification in patients with early stage oral cavity squamous cell carcinoma. Journal of Oral and Maxillofacial Surgery 2007; 65(6): 1191-7.
- Zapata I, Alvarez M, Hidalgo R, Pajares B, Garcia-Anaya MJ, Toledo MD, Trigo JM, Lupiañez-Perez Y, Medina JA and Gomez-Millan JJ: Causes of death in patients with locally advanced head and neck cancer treated with radiotherapy and systemic therapy. BMC Cancer 2019; 19(1): 1-0.
- Itagappa M and Rao SB: Cancer in south Karnataka and its paradoxical relation to diabetes mellitus. Indian Journal of Clinical Biochemistry 2004; 19(1): 6-9.
- Geerlings SE and Hoepelman AI: Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunology & Medical Microbiology 1999; 26(3-4): 259-65.
- Vigneri P, Frasca F, Sciacca L, Pandini G and Vigneri R: Diabetes and cancer. Endocrine-Related Cancer. 2009; 16(4): 1103-23.
- Abhinav RP, Williams J, Livingston P, Anjana RM and Mohan V: Burden of diabetes and oral cancer in India. Journal of Diabetes and its Complications 2020; 2: 107670.
- Park IK, Yang J, Jeong HJ, Bom HS, Harada I, Akaike T, Kim SI and Cho CS: Galactosylated chitosan as a synthetic extracellular matrix for hepatocytes attachment. Biomaterials 2003; 24(13): 2331-7.
- Neville BW and Day TA: Oral cancer and precancerous lesions. CA: a cancer journal for clinicians 2002; 52(4): 195-215.
- Awan KH and Patil S: Association of smokeless tobacco with oral cancer-evidence from the south Asian studies: a systematic review. J Coll Physicians Surg Pak 2016; 26(9): 775-80.
- Offenbacher S, Katz V, Fertik G, Collins J, Boyd D, Maynor G, McKaig R and Beck J: Periodontal infection as a possible risk factor for preterm low birth weight. Journal of Periodontology 1996; 67: 1103-13.
- Ramya NJ, Shekar PC and Reddy BV: Reporting frequency of potentially malignant oral disorders and oral cancer: A 10-year retrospective data analysis in a teaching dental institution. Journal of Dr. NTR University of Health Sciences 2020; 9(2): 124.
- Prabhu S, Shetty K, D’Cunha D and Karkada D: Study of prevalence of work-related stress and co-morbidities and its effect on work performance in KSRTC workers of Dakshina Kannada district, Karnataka, India. International J of Research in Medical Sciences 2015; 3(11): 3161.
- Gaglio BA: Assessing health literacy and health information needs of persons at risk for cardiovascular disease. University of Colorado at Denver 2010.
- Ariyawardana A and Vithanaarachchi N: Awareness of oral cancer and precancer among patients attending a hospital in Sri Lanka. APJCP 2005; 6(1): 58-61.
- Das S and Patro KC: Cancer care in the rural areas of India: a firsthand experience of a clinical oncologist and review of literatures. Journal of Cancer Research and Therapeutics 2010; 6(3): 299.
- Specenier PM and Vermorken JB: Recurrent head and neck cancer: current treatment and future prospects, Expert Rev Anticancer Ther 2008; 8(3): 375-91.
- Bernier J, Domenge C and Ozsahin M: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350: 1945-52.
- Bernier J and Schneider D: Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck. Eur J Cancer 2007; 43(1): 35-45.
- Cooper JS, Pajak TF and Forastiere AA: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350: 1937-44.
- Cooper JS, Zhang Q and Pajak TF: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012; 84: 1198-205.
- Calais G, Alfonsi M and Bardet E: Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst, 1999; 91(24): 2081-6.
- Adelstein DJ, Saxton JP and Lavertu P: Maximizing local control and organ preservation in stage IV squamous cell head and neck cancer with hyper fractionated radiation and concurrent chemotherapy. J Clin Oncol 2002; 20(5): 1405-10.
- Huguenin P, Beer KT and Allal A: Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy. J Clin Oncol 2004; 22(23): 4665–73.
- Schantz SP, Harrison LB and Forastiere A: Tumors of the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, and oropharynx. Philadelphia: Lippincott Williams & Wilkins 2001; 6.
- Leon X, Hitt R and Constenla M: A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy. ClinOncol (R Coll Radiol) 2005; 17(6): 418-24.
- Sunitkumar J, Durga SG and Shilpisrivastava: Genes and oral cancer: Indian J Hum Genet 2014; 20(1): 4-9.
- Chuan W, James D and Natalia S: Targeting head and neck cancer by vaccination, 2018.
- Gettinger S: Targeted therapy in advanced non-small-cell lung cancer. In Seminars in Respiratory and Critical Care Medicine 2008; 29(3): 291-301.
How to cite this article:
Sridhara PB, Chandrashekar S, Shivamallu C, Prasad KS, Chandan D, Patil SS and Gopinath SM: Oral cancer and its epidemiology, therapy and risk factors, case studies in Karnataka: a review. Int J Pharm Sci & Res 2021; 12(11): 5652-61. doi: 10.13040/IJPSR.0975-8232.12(11).5652-61.
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English
IJPSR
Poojitha B. Sridhara, S. Chandrashekar, Chandan Shivamallu, Kollur Shiva Prasad, D. Chandan, Sharanagouda S. Patil and S. M. Gopinath *
Department of Biotechnology, Davangere University, Shivagangotri, Davangere, Karnataka India.
gopinath@davangereuniversity.ac.in
28 September 2020
03 April 2021
25 May 2021
10.13040/IJPSR.0975-8232.12 (11). 5652-61
01 November 2021