|Year : 2016 | Volume
| Issue : 2 | Page : 51-62
An overview of oral carcinogenesis
Shanmugam Manoharan1, Sekar Karthikeyan2, Musthafa Mohamed Essa3, Asokan Manimaran2, Renganathan Selvasundram2
1 Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, India
2 Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India
3 Department of Food Science and Nutrition, Sultan Qaboos University, Muscat, Sultanate of Oman
|Date of Web Publication||11-Apr-2016|
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Chidambaram - 608 002, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Cancer, a life-threatening global burden, is characterized by clonality, autonomy, anaplasia, invasion, and metastasis. Each and every year, the incidence of cancer is increasing worldwide. Most of the cancers arise due to changes in the lifestyle, including tobacco, smoking, and alcohol abuse. Although 100 different types of cancers were reported so far worldwide, oral cancer, skin cancer, mammary cancer, lung cancer, and cervical cancer are the most predominant cancers. Cancer of the oral cavity remains life-threatening disease for more than 50% of the newly diagnosed patients. Lack of awareness, delay in diagnosis, and patient's delay are attributed to the high incidence of oral cancer, despite easy physical examination of the oral cavity. Moreover, the survival outcome of oral cancer patients was not drastically improved despite recent advancement in the treatment of oral cancers. The present review presents the epidemiology and etiology of oral cancer in detail. Furthermore, the biochemical and molecular changes occurring in oral carcinogenesis are also explored. The chemopreventive agents that are evaluated against experimental carcinogenesis are also briefly summarized.
Keywords: Alcohol, chemoprevention, oral cancer, tobacco
|How to cite this article:|
Manoharan S, Karthikeyan S, Essa MM, Manimaran A, Selvasundram R. An overview of oral carcinogenesis. Int J Nutr Pharmacol Neurol Dis 2016;6:51-62
|How to cite this URL:|
Manoharan S, Karthikeyan S, Essa MM, Manimaran A, Selvasundram R. An overview of oral carcinogenesis. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2023 Jan 29];6:51-62. Available from: https://www.ijnpnd.com/text.asp?2016/6/2/51/179964
| Introduction|| |
Cancer, a life-threatening global burden, is characterized by clonality, autonomy, anaplasia, invasion, and metastasis. It comprises a large group of diseases and affects all age groups. Although 100 different types of cancers were reported so far worldwide, oral cancer, skin cancer, mammary cancer, lung cancer, and cervical cancer are the most predominant cancers. The symptoms of cancer depend on its location, size, invasion, and metastasis. Early detection and diagnosis could definitely improve the survival rate as well as the life quality of the patients. Cancer patients, depending on the nature and location of tumors, are subjected to surgery, chemotherapy, radiotherapy, gene therapy, or immunotherapy. ,
Each and every year, the incidence of cancer is increasing worldwide. Most of the cancers arise due to changes in the lifestyle, including tobacco, smoking, and alcohol abuse.  Bacteria, viruses, and other environmental factors are also responsible for rapid increase in the incidence of cancers.  Cancer, a burgeoning threat to the world health, has profound economic and social consequence for people worldwide. According to Ferlay et al. 14.1 million new cancer cases were diagnosed in the year 2012 worldwide.  They also reported that 8.2 million deaths occurred due to cancer in 2012. Epidemiological studies from the USA reported that around 1,658,370 newly diagnosed cancer cases and 589,430 deaths due to these cancers are projected to occur by the year 2015.  In UK, cancer affects around 530 males and 510 females per 100,000 cases every year.  Cancer registry reports from Russia reported that approximately 2.1% of the total country populations are affected by cancer every year.  In Russia, malignant cancers accounts for 15% of all deaths.  Around 2.8 million newly diagnosed cancer cases and 1.96 million cancer-related deaths are reported from China every year. 
In India, cancer is responsible for increased morbidity and mortality and each year around 1 million new cancer cases are diagnosed and around 600,000-700,000 Indians died due to cancer by the year 2012.  Epidemiological studies highlighted that overall cancer incidence in India was lower as compared to developed countries.  At the same time, these studies focused that the relative rates of cancer mortality were higher in India.  The Indian council of medical research recently pointed out that 2.5 million Indians live with a clinical history of cancer. In India, 92.4/100,000 men and 97.4/100,000 women are affected by cancer each year. 
| Oral Cancer|| |
Oral cancer, the cancer of the oral cavity, arises due to the accumulation of multiple genetic alterations in the squamous cells of the oral cavity. Squamous cell carcinoma is the predominant form of oral cancer and accounts for 90% of all oral cancers.  Cancer of the oral cavity remains a life-threatening disease for more than 50% of the newly diagnosed patients. Despite readily available diagnostic tools, lack of awareness, and delayed prognosis have heightened the incidence of oral cancer.  Most of the oral cancer patients' survival outcome depend on the location and stages of the tumors.  It is predicted that the 5 years survival outcome is still at 50% for oral cancer patients, and the survival years have decreased for tongue cancer patients.  Moreover, the survival outcome of oral cancer patients was not drastically improved despite recent advancement in the treatment of oral cancers. Thus, the only key criteria, which could reduce the morbidity and mortality of oral cancer is the early diagnosis.
| Epidemiology Of Oral Cancer|| |
Epidemiological studies from various countries pointed out that around 300,000 people are newly diagnosed with oral cancer every year worldwide and of these two-thirds are from developing countries.  Global variance in the annual incidence rate of oral cancer is due to variation in the consumption or exposure to the risk factors such as tobacco and alcohol.  Cancer of the oral cavity is the sixth most common cancer in the USA, where the annual incidence rate is 10/100,000.  Furthermore, around 8000 deaths due to oral cancer are reported from the USA each year. Around 35,000 Americans are newly diagnosed with oral cancer every year.  The annual incidence rate for oral cancer for men and women together is 10.5/100,000 in the USA. Oral cancer together with pharyngeal cancer attained 7 th position in the incidence in the European Union, where 70,000 new cases are reported each year.  It has been estimated that 1.17% Europeans have lifetime risk for oral cancer development.  Higher oral cancer incidences are reported from France, Hungary, Slovakia, Slovenia, Brazil, and Uruguay every year.  South and Southeast Asia have been pointed out as high incidence regions for oral cancer. India, Bangladesh, Sri Lanka, and Pakistan are regarded as high-risk countries, where oral carcinoma constitutes around 40-50% of all malignancies.  Oral cancer incidence is found to be higher in some of the regions of Hong Kong, Brazil, and Europe.  In Brazil, the annual incidence of oral cancer has been estimated to be 13 cases/100,000.  Taiwan reports that the annual incidence of oral cancer is increasing rapidly and this form of cancer is responsible for the major cause of death in males, ranging in ages between 25 and 44.  In the UK and Canada, oral cancer affects approximately 4000 individuals each year.  In African countries, the incidence of oral cancer is very low and, therefore, it is not a serious problem. However, a study from Sudan reported men are affected by oral cancer more than women.  The incidence and mortality rate of oral cancer was found to be 3.5/100,000 and 1.5/100,000, respectively in China.  The World Health Organization highlighted India as a global epicenter of oral cancer and pointed out oral cancer as a major health challenge and burden in this country.  Furthermore, oral carcinoma accounts for 40% of all cancer-related deaths in India.  In India, every year around 70,000 new cases emerge, and around 48,000 deaths due to oral carcinoma are reported.  In India, the annual incidence is estimated to be 19/100,000, according to databases. 
| Age And Sex Distribution|| |
The persons aged between 40 and 70 years are mainly affected by oral cancer. It has been pointed out that oral cancer patients are mostly at sixties of life at the time of diagnosis.  Male preponderance than female has been reported for oral cancer incidence worldwide.  This might be due to the habits such as tobacco and alcohol use, which are more prevalent in males. Oral cancer affects more men than women in USA.  However, in developing countries such as India, the male-female ratio is closer to 1:1.  The male-female ratio for oral cancer in Japan is estimated to be 3:2. 
| Site Distribution|| |
While tongue cancer is the most predominant cancer among USA and European populations, buccal cancer is found to be more common in Asian countries including India.  Lip, floor of mouth, palate, and gingivae are other less common intraoral sites of the cancer of the oral cavity.
| Risk Factors Of Oral Cancer|| |
The substance or agents that enhance the chances of getting a particular disease are represented as risk factors. Long-term abuse of tobacco and alcohol are identified as the major risk factors in the oral cancer pathogenesis [Figure 1]. Tobacco and betel quid chewing, tobacco, bidi and cigarette smoking and alcohol consumption are important risk factors of oral cancer in India.  Other contributing factors including viral pathogens, increased exposure to sun, nutritional deficiency stemming from low socioeconomic status are recognized as additional risk factors of oral cancer. 
Tobacco, in the form of smoking and chewing, is widely prevalent irrespective of age groups and genders worldwide. Teenagers and youngsters adopt these detrimental habits either from their parents or from the society (friends and relatives etc.).  Despite mounting evidences highlighted the serious health problems associated with tobacco smoking, chewing, and alcohol abuse, these risk factors are still responsible for 30-40% of all cancer-related deaths.  Tobacco contains life-threatening chemicals such as benzo(a)pyrene and nitrosamines. These chemicals cause extensive damage to DNA, contributing to malignant transformation.  A firm association was established between tobacco use and the duration of habits as well as the frequency of tobacco smoking or chewing. 
Worldwide, one billion men and 250 million women are identified as daily smokers.  Cigarette and bidi smokers are 3-4 times more at of developing oral cavity cancers.  Passive smokers are also at increased risk if they were exposed for 10-15 years.  The frequency and the duration of the bidi smoking has been correlated well with the incidence of oral cancer.  Bidi smokers have 3-fold risk to develop oral cancer as compared to cigarette smokers.  The higher amount of nicotine and tar released during bidi smoking is responsible for oral carcinogenesis.  Worldwide meta-analysis data warned that the current smokers have the relative risk rate of 3.43 to get oral carcinoma.  Pipe smoking mainly causes lip cancer and the malignant transformation occurs in the lip area that touches the pipe stem.  Around 100 million Indians are habituated to bidi smoking. The habits of bidi and cigar smoking are more common in rural regions of India. 
Smokeless tobacco refers to the habits of tobacco use other than smoking. Smokeless tobacco includes tobacco chewing, betel quid chewing, and snuffs. Smokeless tobacco has around 25 powerful carcinogens, which can cause extensive damage to DNA. Some of the potent carcinogens in smokeless tobacco include tobacco-specific nitrosamines, formaldehyde, and benzo(a)pyrene.  It has been reported that smokeless tobacco consumption is highly prevalent in Indian populations as compared to tobacco smoking and alcohol consumption.  Long-term smokeless tobacco usage increased the oral cancer risk and is mainly attributed to the presence of tobacco-specific nitrosamines. 
Betel quid chewing
In many parts of the world, especially South Asia and South East Asia, the habits of betel quid (made up of areca nut and lime wrapped in a betel leaf) chewing is commonly prevalent and is accepted as a social custom.  It has been reported that those who are habituated to betel quid chewing for 20 years and chewing 10 times daily have an increased risk to get oral cancer.  Betel quid chewing enhances the risk of oral cancer development to a several fold. Betel quid mediates carcinogenic process through carcinogenic nitrosamines and by generating excess reactive oxygen species (ROS) in the oral cavity.  Excessive ROS generation is due to auto-oxidation of polyphenols present in the areca nut. Areca nut chewing is also recognized as an important risk factor of oral cancer.  It has been pointed out that keeping the betel quid for a longer time in the mouth enhance the risk to a greater extent. 
World health organization reported that around 2 billion people are habituated to alcohol consumption worldwide. Approximately, 80 million people worldwide are affected by alcohol-induced disorders.  Alcohol drinkers have a 3-fold increased risk for oral cancer than nondrinkers.  It has been documented that heavy alcohol drinking accounts for 7-19% of all oral cancers.  Acetaldehyde, the carcinogenic metabolite of alcohol, is responsible for oral carcinogenesis.  A case study highlighted that 70% of oral cancer patients are heavy consumers of alcohol.  Alcohol in combination with tobacco profoundly enhances the risk of oral cancer development.  Habituation or addiction to tobacco and alcohol use is on the rise in younger generations.  A 35-40-fold increase in risk was reported in subjects who are habituated to both alcohol consumption and tobacco use.  In India, tobacco and alcohol use together, are recognized as the primary behavioral risk factors in more than 75% of oral cancer.  An Indian study reported that the synergetic risk of tobacco and alcohol to induce oral cancer was 24-fold. 
Diet and nutrition
Poor nutrition, lack of exercise, and obesity accounts for 30-40% of all cancers. A diet deficient in antioxidants, vitamins, minerals, and trace elements predisposes toward oral cancer development.  People who do not consume enough vegetables and fruits are at increased risk of oral cancer development.  High consumption of red meat and low intake of leafy vegetables enhance the risk of developing oral cancer.  Fish and milk consumption reduced the risk of oral cancer. 
Human papillomaviruses (HPV), especially the subtypes HPV 16 and HPV 18, and herpes simplex viruses are significantly associated with the development of oral cancer.  The biopsy from 25% of the oral cancer patients revealed the presence of HPV. 
Other risk factors of oral cancer
A significant positive association has been reported between periodontal disease and oral cancer risk.  Dry snuff use has been associated with an increased risk than moist snuff.  Individuals who work outdoors are constantly exposed to ultraviolet (UV) rays from sunlight. Lip cancer is the predominant form of cancer in these outdoor workers.  Some of the unproven or controversial risk factors of oral cancer include mouthwash use and irritation from poorly fitting dentures.  Immunocompromised individuals were found to be more susceptible to oral cancer.  Reports pointed out that patients' first-degree relatives are more susceptible to develop oral cancer.  Individuals with a defect in enzymes involved in the xenobiotic metabolizing pathway could be at enhanced risk to develop oral carcinoma. 
| Precancerous Lesions|| |
The sequential histological alterations occurring in oral malignant transformation involves alterations from normal to hyperkeratosis, hyperplasia, and dysplasia and then to carcinoma in situ and invasive malignant cancer. 
Oral malignant cancer proceeds in a step-wise manner and usually emerges as precancerous lesions such as leukoplakia, erythroplakia, and oral submucous fibrosis.  The term oral leukoplakia represents a white patch in the mouth which cannot be eliminated by scraping and can either transform into invasive carcinoma or regress spontaneously.  It has been pointed out that the rate of leukoplakia transformation into malignant cancer varies between 17% and 24% in the United States.  However, lower rates of malignant transformation have been reported in developing countries.  Around 10% of leukoplakia turn into malignant cancer, according to Jayanthi et al.  It has been reported that 53% of patients with Candida positive leukoplakia developed oral carcinoma. 
This precancerous condition is diagnosed with fiery red patch on the mucosa. The red patch cannot be characterized clinically as any other definable diseases and more likely to turn into dysplasia or malignancy than leukoplakia. Bleeding occur if erythroplakia is scraped. 
Oral submucous fibrosis
Long-term betel quid chewing leads to a precancerous condition in the oral mucosa known as oral submucous fibrosis. This condition is more prevalent in India and South East Asia.  Oral submucous fibrosis, if untreated, definitely turn into malignant cancer. Oral submucous fibrosis is characterized by inflammation and fibrosis of the submucosa tissues with difficulty while opening mouth. 
| Signs And Symptoms Of Oral Cancer|| |
Although early precancerous and cancerous lesions are symptomless or unable to elicit symptoms, cancer patients with advanced tumor stage may suffer from significant pain, difficulty swallowing, chewing, and eating. An unheal sore in the mouth is the most common symptom of oral cancer. Red or white lesions in the mouth, voice hoarseness, and bad breath are other signs and symptoms of oral cancer. 
| Diagnosis|| |
Tumor tissues of various cancers have different blend of genetic and epigenetic alterations. The diagnostic modalities to confirm the presence of malignant tumors in the oral cavity include cytology and brush biopsy (oralCDx Brush Test), fine-needle aspiration, toludine blue staining, visualization based adjunctive techniques (optical coherence tomography, and autofluorescence technique), and imaging studies (computed tomography, magnetic resonance imaging and position emission tomography).  Self-examination by the individuals could help to detect oral cancer at an early stage. Routine screening exams on the oral cavity could help detect the abnormal lesions early.  Delay in the diagnosis often results either from the unsuspecting patient's neglect to have a check-up, or the clinician's late recommendation to further evaluate the suspected tissue.  The clinician should thoroughly check any abnormal findings, not only in the internal site but also in the extraoral head and neck tissues. The diagnostic delay could lead to poor life quality as well as low survival outcome.  Histopathological examinations in the suspected biopsy by the pathologist serve as the best diagnostic criteria to diagnose oral precancerous and cancerous lesions.  Recent advancement in molecular biology techniques could help detect the precancerous and cancerous lesions at an early stage. 
| Tumor Staging|| |
Tumor-lymph node-metastasis (TNM) staging is commonly employed to assess the tumor stage of the patients suffering from oral cancer. TNM assess the tumor stage based on the size of the tumor (T), lymph node involvement (N), and metastasis (M). The staging of TNM is given in [Figure 2].
|Figure 2: Clinical staging of oral cancer, treatment modalities, and prognosis by clinical stage|
Click here to view
| Biochemical And Molecular Changes In Oral Cancer|| |
Malignant tumors progress, invade and spread to other parts of the body through dysregulation in novel biochemical and molecular events such as apoptosis, cell proliferation, inflammation, and angiogenesis. Dysregulation in these mechanistic pathways could help the transformed cells to grow and progress further. Inactivation of tumor suppressor genes or amplification of oncogenes is documented as hallmark of several carcinogenesis. Overproductions of ROS accompanied by insufficient antioxidant potential and defect in Phase I and II detoxification mechanism could also contribute to neoplastic transformation. The molecular changes that are reported in oral carcinogenesis is given in [Table 1].
| Prevention|| |
Oral cancer development can be prevented by avoiding the use of tobacco, alcohol, and betel nuts. Quitting the habits of tobacco, bidi and cigarette smoking, and alcohol consumption could reduce the development of oral malignancy.  The risk of developing oral carcinoma can also be prevented by limiting the exposure to UV light and eating lots of fruits and leafy vegetables. 
| Treatment|| |
The anatomical constraint of the head and neck make the treatment of oral cancer difficult. The current treatment employed for oral cancer patients include surgery, radiation therapy, and chemotherapy. The treatment is recommended in combination or alone based on the severity of the tumor (tumor stage) and health status and life style of the patients.  The treatment plan is discussed and developed by multidisciplinary team, which include surgeons, oncologist, radiologist, dentists, and rehabilitation specialists.  Moreover, the concurrence from patient's family should also be obtained before beginning the treatment. The patients have to face a lot of problems such as changes in appearance and organ dysfunctions, even after a successful treatment.
| 7,12-Dimethylbenz(A)Anthracene Induced Oral Carcinogenesis|| |
The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), is commonly utilized as a carcinogen to induce tumors in the buccal pouches of golden Syrian hamsters. Buccal pouches, a pocket like anatomy, exposed to repeated topical application of DMBA resulted in well-developed oral squamous cell carcinoma. DMBA can cause neoplasm by inducing severe inflammation and dysplasia in the buccal pouches in addition to causing extensive oxidative damage to DNA.  Accumulated evidences pointed out that DMBA mediated oral carcinogenesis resembles human oral cancer in several aspects including at histological, morphological, biochemical, and molecular aspects.  DMBA induced hamster buccal pouch carcinogenesis is therefore preferred to study the tumor preventive potential of natural products and their bioactive constituents.
| Chemoprevention|| |
The strategy, which uses the natural products, phytoconstituents or synthetic entities to suppress, inhibit, reverse or regress the neoplastic transformation, is known as chemoprevention. Chemopreventive agents exert their anticarcinogenic potential through their diverse pharmacological efficacy, including anti-inflammatory, antioxidant, apoptotic, and anti-angiogenic properties.  Biomarkers, biochemical, or molecular markers, plays a vital role in determining the health status of the patients. The level or the status of a particular cancer biomarker could help assess the cancer stage as well as to plan the treatment strategy.  Biomarker status could also reflect the safety and efficacy of the chemopreventive agents.  Easy anatomical access of the oral cavity could help to assess and follow the chemopreventive potential of the test compound in various stages of tumorigenesis.  The chemopreventive agents evaluated against oral carcinogenesis is given in [Table 2].
|Table 2: Chemopreventive agents tested against experimental oral carcinogenesis |
Click here to view
| Conclusion|| |
Oral carcinoma, the cancer of the oral cavity, has multifactorial etiology and arises mainly due to tobacco and alcohol addiction, which cause divergent biochemical and molecular abnormalities in the oral cavity. Since it is a well-known fact that the risk factors of oral cancer are modifiable, the government should take intensive effort to create awareness on oral cancer among the society to control the incidence of oral cancer. Thus, this form of cancer not only imposes a significant health burden, but also affects the overall life quality of the oral cancer patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Are C, Rajaram S, Are M, Raj H, Anderson BO, Chaluvarya Swamy R, et al.
A review of global cancer burden: Trends, challenges, strategies, and a role for surgeons. J Surg Oncol 2013;107:221-6.
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al.
Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 2014;64:252-71.
McCormack VA, Boffetta P. Today′s lifestyles, tomorrow′s cancers: Trends in lifestyle risk factors for cancer in low- and middle-income countries. Ann Oncol 2011;22:2349-57.
Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al.
Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097-116.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al.
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.
Savage P, Sharkey R, Kua T, Papanastasopoulos P, McDonald-Burrows Z, Hassan S, et al.
Clinical characteristics and outcomes for patients with an initial emergency presentation of malignancy: A 15 month audit of patient level data. Cancer Epidemiol 2015;39:86-90.
Kaprin AD, Starinsky VV, Petrova GV. Status of oncology care in Russia in 2012. In: The state of cancer care in Russia in 2012, Moscow: Herzen Moscow Research Cancer Institute Publishing; 2013. p. 112-86.
Chissov V, Starinsky V, Petrova G. In: Cancer Statistics in Russia in 2011. Moscow: Herzen Moscow Research Cancer Institute Publishing; 2013. p. 8-86.
Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, Fan L, Li J, Chavarri-Guerra Y, et al.
Challenges to effective cancer control in China, India, and Russia. Lancet Oncol 2014;15:489-538.
Mallath MK, Taylor DG, Badwe RA, Rath GK, Shanta V, Pramesh CS, et al.
The growing burden of cancer in India: Epidemiology and social context. Lancet Oncol 2014;15:e205-12.
Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer risk and diet in India. J Postgrad Med 2003;49:222-8.
National Cancer Registry Programme (Indian Council of Medical Research). Development of an Atlas of Cancer in India. Ch. 4. Available from: http://www.canceratlasindia.org/chapter4_1.aspx
. Maintained by National Cancer Institute (NCI, USA). [Last updated on 2015 Mar 02].
Bagan J, Sarrion G, Jimenez Y. Oral cancer: Clinical features. Oral Oncol 2010;46:414-7.
Esmaelbeigi F, Hadji M, Harirchi I, Omranipour R, vand Rajabpour M, Zendehdel K. Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran. Arch Iran Med 2014;17:253-7.
Jones KR, Lodge-Rigal RD, Reddick RL, Tudor GE, Shockley WW. Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity. Arch Otolaryngol Head Neck Surg 1992;118:483-5.
Chinn SB, Myers JN. Oral cavity carcinoma: Current management, controversies, and future directions. J Clin Oncol 2015;33:3269-76.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45:309-16.
Agrawal M, Jain S, Maitin N, Gupta T, Maitin S. Prevalence and predictors of tobacco use among general public of Gorakhpur district, India. J Oral Biol Craniofac Res 2015;5:16-20.
Feller L, Lemmer J. Oral squamous cell carcinoma: Epidemiology, clinical presentation and treatment. J Cancer Ther 2012;3:263-8.
Rosebush MS, Rao SK, Samant S, Gu W, Handorf CR, Pfeffer LM, et al.
Oral cancer: Enduring characteristics and emerging trends. J Mich Dent Assoc 2012;94:64-8.
Garavello W, Bertuccio P, Levi F, Lucchini F, Bosetti C, Malvezzi M, et al.
The oral cancer epidemic in central and eastern Europe. Int J Cancer 2010;127:160-71.
Warnakulasuriya S. Living with oral cancer: Epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol 2010;46:407-10.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: Differences by country, sex and anatomic site. Oral Oncol 2014;50:387-403.
Carvalho Mde V, Iglesias DP, do Nascimento GJ, Sobral AP. Epidemiological study of 534 biopsies of oral mucosal lesions in elderly Brazilian patients. Gerodontology 2011;28:111-5.
Lian IeB, Tseng YT, Su CC, Tsai KY. Progression of precancerous lesions to oral cancer: Results based on the Taiwan National Health Insurance Database. Oral Oncol 2013;49:427-30.
Canadian Cancer Society′s Steering Committee on Cancer Statistics. Canadian Cancer Statistics 2012. Toronto, ON: Canadian Cancer Society; 2012.
Idris AM, Ahmed HM, Mukhtar BI, Gadir AF, el-Beshir EI. Descriptive epidemiology of oral neoplasms in Sudan 1970-1985 and the role of toombak. Int J Cancer 1995;61:155-8.
Center CNC. Oral Cavity and Pharynx but Nasopharynx. Chinese Cancer Registry Annual Report, 2011. Beijing: MMS Press; 2012. p. 38-40.
Gupta B, Ariyawardana A, Johnson NW. Oral cancer in India continues in epidemic proportions: Evidence base and policy initiatives. Int Dent J 2013;63:12-25.
Khandekar SP, Bagdey PS, Tiwari RR. Oral cancer and some epidemiological factors: A hospital-based study. Indian J Community Med 2006;31:157-9.
Elango JK, Sundaram KR, Gangadharan P, Subhas P, Peter S, Pulayath C, et al.
Factors affecting oral cancer awareness in a high-risk population in India. Asian Pac J Cancer Prev 2009;10:627-30.
National Cancer Registry Programme. Three-year Report of Population-based Cancer Registries 2006-2008. Incidence and Distribution of Cancer. Bangalore: Indian Council of Medical Research; 2010.
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212-36.
Ries LA, Eisner MP, Kosary CL. SEER Cancer Statistics Review, 1975-2000. Bethesda, MD: National Cancer Institute; 2003.
American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society; 2013.
Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med 2001;345:1890-900.
Japan Society for Head and Neck Cancer Registry Committee. Report of head and neck cancer registry of Japan. Clinical statistics of registered patients, 2002. Jpn J Head Neck Cancer 2006;32:15-34.
Krishna Rao SV, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade - An update (2000-2012). Asian Pac J Cancer Prev 2013;14:5567-77.
Nagpal R, Nagpal N, Mehendiratta M, Marya CM, Rekhi A. Usage of betel quid, areca nut, tobacco, alcohol and level of awareness towards their adverse effects on health in a North Indian rural population. Oral Health Dent Manag 2014;13:81-6.
Conway DI, Petticrew M, Marlborough H, Berthiller J, Hashibe M, Macpherson LM. Socioeconomic inequalities and oral cancer risk: A systematic review and meta-analysis of case-control studies. Int J Cancer 2008;122:2811-9.
Sridharan G. Epidemiology, control and prevention of tobacco induced oral mucosal lesions in India. Indian J Cancer 2014;51:80-5.
Ram H, Sarkar J, Kumar H, Konwar R, Bhatt ML, Mohammad S. Oral cancer: Risk factors and molecular pathogenesis. J Maxillofac Oral Surg 2011;10:132-7.
Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biörklund A, et al.
Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: A population-based case-referent study in Sweden. Cancer 1998;82:1367-75.
Johnson N. Tobacco use and oral cancer: A global perspective. J Dent Educ 2001;65:328-39.
Petti S. Lifestyle risk factors for oral cancer. Oral Oncol 2009;45:340-50.
Wyss A, Hashibe M, Chuang SC, Lee YC, Zhang ZF, Yu GP, et al.
Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol 2013;178:679-90.
Radoï L, Paget-Bailly S, Cyr D, Papadopoulos A, Guida F, Schmaus A, et al.
Tobacco smoking, alcohol drinking and risk of oral cavity cancer by subsite: Results of a French population-based case-control study, the ICARE study. Eur J Cancer Prev 2013;22:268-76.
Jayalekshmi PA, Gangadharan P, Akiba S, Koriyama C, Nair RR. Oral cavity cancer risk in relation to tobacco chewing and bidi smoking among men in Karunagappally, Kerala, India: Karunagappally cohort study. Cancer Sci 2011;102:460-7.
Rahman M, Sakamoto J, Fukui T. Bidi smoking and oral cancer: A meta-analysis. Int J Cancer 2003;106:600-4.
Güneri P, Cankaya H, Yavuzer A, Güneri EA, Erisen L, Ozkul D, et al.
Primary oral cancer in a Turkish population sample: Association with sociodemographic features, smoking, alcohol, diet and dentition. Oral Oncol 2005;41:1005-12.
Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, et al.
Tobacco smoking and cancer: A meta-analysis. Int J Cancer 2008;122:155-64.
Bou Fakhreddine HM, Kanj AN, Kanj NA. The growing epidemic of water pipe smoking: Health effects and future needs. Respir Med 2014;108:1241-53.
Panchamukhi PR, Woolery T, Nayantara SN. Economics of bidis in India. In: Gupta PC, Asma S, editors. Bidi Smoking and Public Health. New Delhi: Ministry of Health and Family Welfare, Government of India; 2008. p. 167-95.
Grasso P, Mann AH. Smokeless tobacco and oral cancer: An assessment of evidence derived from laboratory animals. Food Chem Toxicol 1998;36:1015-29.
Madani AH, Dikshit M, Bhaduri D. Risk for oral cancer associated to smoking, smokeless and oral dip products. Indian J Public Health 2012;56:57-60.
International Agency for Research on Cancer. Smokeless Tobacco and Some Tobacco-specific N-nitrosamines. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 89. Lyon, France: World Health Organization, International Agency for Research on Cancer; 2007. p. 153-88.
Guha N, Warnakulasuriya S, Vlaanderen J, Straif K. Betel quid chewing and the risk of oral and oropharyngeal cancers: A meta-analysis with implications for cancer control. Int J Cancer 2014;135:1433-43.
Anand R, Dhingra C, Prasad S, Menon I. Betel nut chewing and its deleterious effects on oral cavity. J Cancer Res Ther 2014;10:499-505.
Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: A review of agents and causative mechanisms. Mutagenesis 2004;19:251-62.
Li YC, Chang JT, Chiu C, Lu YC, Li YL, Chiang CH, et al.
Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells. Mol Carcinog 2015. [doi: 10.1002/mc.22344].
Wen CP, Tsai MK, Chung WS, Hsu HL, Chang YC, Chan HT, et al.
Cancer risks from betel quid chewing beyond oral cancer: A multiple-site carcinogen when acting with smoking. Cancer Causes Control 2010;21:1427-35.
Balhara YP, Mathur S. Alcohol: A major public health problem-South Asian perspective. Addict Disord Their Treat 2012;11:101-20.
Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, et al.
Carcinogenicity of alcoholic beverages. Lancet Oncol 2007;8:292-3.
Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, et al.
Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst 2007;99:777-89.
Marttila E, Uittamo J, Rusanen P, Lindqvist C, Salaspuro M, Rautemaa R. Acetaldehyde production and microbial colonization in oral squamous cell carcinoma and oral lichenoid disease. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:61-8.
Turati F, Garavello W, Tramacere I, Pelucchi C, Galeone C, Bagnardi V, et al.
A meta-analysis of alcohol drinking and oral and pharyngeal cancers: Results from subgroup analyses. Alcohol Alcohol 2013;48:107-18.
Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, et al.
Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009;18:541-50.
Pawar HJ, Dhumale GB, Singh KK. Epidemiological determinants of oral cancer in a rural area of Maharashtra state, India. Int J Healthc Biomed Res 2014;2:186-94.
Ferreira Antunes JL, Toporcov TN, Biazevic MG, Boing AF, Scully C, Petti S. Joint and independent effects of alcohol drinking and tobacco smoking on oral cancer: A large case-control study. PLoS One 2013;8:e68132.
Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, et al.
Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer 2003;105:681-6.
Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J, et al.
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 Oncol 2008;44:446-54.
Popkin BM. Understanding global nutrition dynamics as a step towards controlling cancer incidence. Nat Rev Cancer 2007;7:61-7.
Warnakulasuriya S. Food, nutrition and oral cancer. In: Wilson M, editor. Food Constituents and Oral Health. Current Status and Future Prospects. Vol. 1: Woodhead Publishing Limited; Gread Abington, Cambridge; 2009. p. 273-95.
Helen-Ng LC, Razak IA, Ghani WM, Marhazlinda J, Norain AT, Raja Jallaludin RL, et al.
Dietary pattern and oral cancer risk - A factor analysis study. Community Dent Oral Epidemiol 2012;40:560-6.
Gangane N, Chawla S, Anshu, Gupta SS, Sharma SM. Reassessment of risk factors for oral cancer. Asian Pac J Cancer Prev 2007;8:243-8.
Deng Z, Uehara T, Maeda H, Hasegawa M, Matayoshi S, Kiyuna A, et al.
Epstein-Barr virus and human papillomavirus infections and genotype distribution in head and neck cancers. PLoS One 2014;9:e113702.
Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al.
Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709-20.
Javed F, Warnakulasuriya S. Is there a relationship between periodontal disease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol 2016;97:197-205.
Janbaz KH, Qadir MI, Basser HT, Bokhari TH, Ahmad B. Risk for oral cancer from smokeless tobacco. Contemp Oncol (Pozn) 2014;18:160-4.
Johnson NW, Warnakulasuriya S, Gupta PC, Dimba E, Chindia M, Otoh EC, et al.
Global oral health inequalities in incidence and outcomes for oral cancer: Causes and solutions. Adv Dent Res 2011;23:237-46.
Gandini S, Negri E, Boffetta P, La Vecchia C, Boyle P. Mouthwash and oral cancer risk quantitative meta-analysis of epidemiologic studies. Ann Agric Environ Med 2012;19:173-80.
Jewett A, Head C, Cacalano NA. Emerging mechanisms of immunosuppression in oral cancers. J Dent Res 2006;85:1061-73.
Burgaz S, Coskun E, Demircigil GC, Kocabas NA, Cetindag F, Sunter O, et al.
Micronucleus frequencies in lymphocytes and buccal epithelial cells from patients having head and neck cancer and their first-degree relatives. Mutagenesis 2011;26:351-6.
Sato M, Sato T, Izumo T, Amagasa T. Genetic polymorphism of drug-metabolizing enzymes and susceptibility to oral cancer. Carcinogenesis 1999;20:1927-31.
Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007;36:575-80.
Arnaoutakis D, Bishop J, Westra W, Califano JA. Recurrence patterns and management of oral cavity premalignant lesions. Oral Oncol 2013;49:814-7.
Nair DR, Pruthy R, Pawar U, Chaturvedi P. Oral cancer: Premalignant conditions and screening - An update. J Cancer Res Ther 2012;8 Suppl 1:S57-66.
Foy JP, Bertolus C, William WN Jr., Saintigny P. Oral premalignancy: The roles of early detection and chemoprevention. Otolaryngol Clin North Am 2013;46:579-97.
Lee JJ, Hong WK, Hittelman WN, Mao L, Lotan R, Shin DM, et al.
Predicting cancer development in oral leukoplakia: Ten years of translational research. Clin Cancer Res 2000;6:1702-10.
Jayanthi JL, Mallia RJ, Shiny ST, Baiju KV, Mathews A, Kumar R, et al.
Discriminant analysis of autofluorescence spectra for classification of oral lesions in vivo
. Lasers Surg Med 2009;41:345-52.
Rhodus NL, Kerr AR, Patel K. Oral cancer: Leukoplakia, premalignancy, and squamous cell carcinoma. Dent Clin North Am 2014;58:315-40.
Amagasa T. Oral premalignant lesions. Int J Clin Oncol 2011;16:1-4.
Palmer O, Grannum R. Oral cancer detection. Dent Clin North Am 2011;55:537-48, viii-ix.
Arakeri G, Brennan PA. Oral submucous fibrosis: An overview of the aetiology, pathogenesis, classification, and principles of management. Br J Oral Maxillofac Surg 2013;51:587-93.
American Cancer Society. Cancer Facts & Figures 2015. Atlanta, GA: American Cancer Society; 2015.
Mehrotra R, Gupta DK. Exciting new advances in oral cancer diagnosis: Avenues to early detection. Head Neck Oncol 2011;3:33.
Elango KJ, Anandkrishnan N, Suresh A, Iyer SK, Ramaiyer SK, Kuriakose MA. Mouth self-examination to improve oral cancer awareness and early detection in a high-risk population. Oral Oncol 2011;47:620-4.
Seoane J, Takkouche B, Varela-Centelles P, Tomás I, Seoane-Romero JM. Impact of delay in diagnosis on survival to head and neck carcinomas: A systematic review with meta-analysis. Clin Otolaryngol 2012;37:99-106.
Silverman S. In: Oral Cancer. 5 th
ed. Hamilton, ON, London: BC Decker; 2003. p. 1-128.
Poh CF, Ng S, Berean KW, Williams PM, Rosin MP, Zhang L. Biopsy and histopathologic diagnosis of oral premalignant and malignant lesions. J Can Dent Assoc 2008;74:283-8.
Mehrotra R, Gupta A, Singh M, Ibrahim R. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions. Mol Cancer 2006;5:11.
Noguti J, Alvarenga TA, Marchi P, Oshima CT, Andersen ML, Ribeiro DA. The influence of sleep restriction on expression of apoptosis regulatory proteins p53, Bcl-2 and Bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. J Oral Pathol Med 2015;44:222-8.
Camisasca DR, Honorato J, Bernardo V, da Silva LE, da Fonseca EC, de Faria PA, et al.
Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma. Oral Oncol 2009;45:225-33.
Zhang M, Zhang P, Zhang C, Sun J, Wang L, Li J, et al.
Prognostic significance of Bcl-2 and Bax protein expression in the patients with oral squamous cell carcinoma. J Oral Pathol Med 2009;38:307-13.
Zhang K, Jiao K, Xing Z, Zhang L, Yang J, Xie X, et al.
Bcl-xL overexpression and its association with the progress of tongue carcinoma. Int J Clin Exp Pathol 2014;7:7360-77.
Adachi M, Imai K. The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2. Cell Death Differ 2002;9:1240-7.
Kato K, Kawashiri S, Yoshizawa K, Kitahara H, Okamune A, Sugiura S, et al.
Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: Correlation with clinicopathological features and prognosis. J Oral Pathol Med 2011;40:693-8.
Basnaker M, Sp S, Bnvs S. Cyclin d1 gene expression in oral mucosa of tobacco chewers" - An immunohistochemical study. J Clin Diagn Res 2014;8:ZC70-5.
Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, et al.
Preclinical characterization of the CDK4/6 inhibitor LY2835219: In-vivo
cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs 2014;32:825-37.
Sun HB, Zheng HY, Yan X. Survivin silencing enhances radiosensitivity in oral squamous cell carcinoma cell. Eur Rev Med Pharmacol Sci 2014;18:2678-86.
Abid AM, Merza MS. Immunohistochemical expression of cyclin D1 and NF-kB, p65 in oral lichen planus and oral squamous cell carcinoma (Comparative study). J Baghdad Coll Dent 2014;26:80-7.
Johnson J, Shi Z, Liu Y, Stack MS. Inhibitors of NF-kappaB reverse cellular invasion and target gene upregulation in an experimental model of aggressive oral squamous cell carcinoma. Oral Oncol 2014;50:468-77.
Li TJ, Cui J. COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma. Asian Pac J Trop Med 2013;6:640-3.
Yang JS, Wu CC, Lee HZ, Hsieh WT, Tang FY, Bau DT, et al.
Suppression of the TNF-alpha level is mediated by Gan-Lu-Yin (traditional Chinese medicine) in human oral cancer cells through the NF-kappa B, AKT, and ERK-dependent pathways. Environ Toxicol 2015. [doi: 10.1002/mc.22127].
Chuang JY, Huang YL, Yen WL, Chiang IP, Tsai MH, Tang CH. Syk/JNK/AP-1 signaling pathway mediates interleukin-6-promoted cell migration in oral squamous cell carcinoma. Int J Mol Sci 2014;15:545-59.
Kishimoto K, Yoshida S, Ibaragi S, Yoshioka N, Okui T, Hu GF, et al.
Hypoxia-induced up-regulation of angiogenin, besides VEGF, is related to progression of oral cancer. Oral Oncol 2012;48:1120-7.
Aggarwal S, Devaraja K, Sharma SC, Das SN. Expression of vascular endothelial growth factor (VEGF) in patients with oral squamous cell carcinoma and its clinical significance. Clin Chim Acta 2014;436:35-40.
Patel BP, Shah PM, Rawal UM, Desai AA, Shah SV, Rawal RM, et al.
Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma. J Surg Oncol 2005;90:81-8.
Fan HX, Li HX, Chen D, Gao ZX, Zheng JH. Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: Relationships and prognostic implications. J Exp Clin Cancer Res 2012;31:90.
Manoharan S, Wani SA, Vasudevan K, Manimaran A, Prabhakar MM, Karthikeyan S, et al.
Saffron reduction of 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Asian Pac J Cancer Prev 2013;14:951-7.
Palanimuthu D, Baskaran N, Silvan S, Rajasekaran D, Manoharan S. Lupeol, a bioactive triterpene, prevents tumor formation during 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis. Pathol Oncol Res 2012;18:1029-37.
Baskaran N, Manoharan S, Karthikeyan S, Prabhakar MM. Chemopreventive potential of coumarin in 7,12-dimethylbenz[a] anthracene induced hamster buccal pouch carcinogenesis. Asian Pac J Cancer Prev 2012;13:5273-9.
Karthikeyan S, Srinivasan R, Wani SA, Manoharan S. Chemopreventive potential of chrysin in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Int J Nutr Pharmacol Neurol Dis 2013;3:46-53.
Manoharan S, Kavitha K, Balakrishnan S, Rajalingam K. Clerodendron inerme protects cellular integrity during 7,12-dimethylbenz[A]-anthracene induced hamster buccal pouch carcinogenesis. Afr J Tradit Complement Altern Med 2008;5:213-22.
Silvan S, Manoharan S, Baskaran N, Karthikeyan S, Prabhakar MM. Protective effect of apigenin on 7,12-dimethylbenz(a)anthracene induced glycoconjugates in the plasma and buccal mucosa of golden Syrian hamsters. Int J Pharm Sci Res 2011;2:1753-8.
Petersen PE. Oral cancer prevention and control - The approach of the World Health Organization. Oral Oncol 2009;45:454-60.
Chainani-Wu N, Epstein J, Touger-Decker R. Diet and prevention of oral cancer: Strategies for clinical practice. J Am Dent Assoc 2011;142:166-9.
Deng H, Sambrook PJ, Logan RM. The treatment of oral cancer: An overview for dental professionals. Aust Dent J 2011;56:244-52, 341.
Brody S, Omer O, McLoughlin J, Stassen L. The dentist′s role within the multi-disciplinary team maintaining quality of life for oral cancer patients in light of recent advances in radiotherapy. J Ir Dent Assoc 2013;59:137-46.
Manoharan S, Panjamurthy K, Pugalendi P, Balakrishnan S, Rajalingam K, Vellaichamy L, et al.
Protective role of withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a] anthracene induced oral carcinogenesis. Afr J Tradit Complement Altern Med 2008;6:94-102.
Nagini S. Of humans and hamsters: The hamster buccal pouch carcinogenesis model as a paradigm for oral oncogenesis and chemoprevention. Anticancer Agents Med Chem 2009;9:843-52.
Szumilo J, Podlodowska J, Podlodowski W, Staroslawska E, Burdan F. Chemoprevention of oral cancer - Clinical and experimental studies. Pol Merkur Lekarski 2012;32:138-42.
Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS. Cancer biomarkers - Current perspectives. Indian J Med Res 2010;132:129-49.
Rahman MA, Amin AR, Shin DM. Chemopreventive potential of natural compounds in head and neck cancer. Nutr Cancer 2010;62:973-87.
Gillenwater A, Papadimitrakopoulou V, Richards-Kortum R. Oral premalignancy: New methods of detection and treatment. Curr Oncol Rep 2006;8:146-54.
Cho JH, Shin JC, Cho JJ, Choi YH, Shim JH, Chae JI. Esculetin (6,7-dihydroxycoumarin): A potential cancer chemopreventive agent through suppression of Sp1 in oral squamous cancer cells. Int J Oncol 2015;46:265-71.
Kim DW, Ko SM, Jeon YJ, Noh YW, Choi NJ, Cho SD, et al.
Anti-proliferative effect of honokiol in oral squamous cancer through the regulation of specificity protein 1. Int J Oncol 2013;43:1103-10.
Li F, Shanmugam MK, Siveen KS, Wang F, Ong TH, Loo SY, et al.
Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers. Oncotarget 2015;6:5147-63.
Luo Q, Hu D, Hu S, Yan M, Sun Z, Chen F. In vitro
and in vivo
anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma. BMC Cancer 2012;12:517.
Hsu WH, Lee BH, Pan TM. Effects of red mold dioscorea on oral carcinogenesis in DMBA-induced hamster animal model. Food Chem Toxicol 2011;49:1292-7.
El-Rouby DH. Histological and immunohistochemical evaluation of the chemopreventive role of lycopene in tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Arch Oral Biol 2011;56:664-71.
Fong LY, Jiang Y, Rawahneh ML, Smalley KJ, Croce CM, Farber JL, et al.
Zinc supplementation suppresses 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis. Carcinogenesis 2011;32:554-60.
Lajolo C, Sgambato A, Maiorano E, Lucchese A, Capodiferro S, Favia G, et al.
Calcium glucarate inhibits DMBA-induced oral carcinogenesis in the hamster: Histomorphometric evaluation. Anticancer Res 2010;30:843-9.
Grawish ME, Zaher AR, Gaafar AI, Nasif WA. Long-term effect of Spirulina platensis
extract on DMBA-induced hamster buccal pouch carcinogenesis (immunohistochemical study). Med Oncol 2010;27:20-8.
Meier JD, Enepekides DJ, Poirier B, Bradley CA, Albala JS, Farwell DG. Treatment with 1-alpha, 25-dihydroxyvitamin D3 (Vitamin D3) to inhibit carcinogenesis in the hamster buccal pouch model. Arch Otolaryngol Head Neck Surg 2007;133:1149-52.
Li P, Ge HB, Sun Z. Inhibiting effects of GW2974 on DMBA-induced hamster buccal pouch carcinogenesis. Zhonghua Kou Qiang Yi Xue Za Zhi 2007;42:432-5.
Miller EG, Porter JL, Binnie WH, Guo IY, Hasegawa S. Further studies on the anticancer activity of citrus limonoids. J Agric Food Chem 2004;52:4908-12.
Bhuvaneswari V, Abraham SK, Nagini S. Combinatorial antigenotoxic and anticarcinogenic effects of tomato and garlic through modulation of xenobiotic-metabolizing enzymes during hamster buccal pouch carcinogenesis. Nutrition 2005;21:726-31.
Subapriya R, Bhuvaneswari V, Nagini S. Ethanolic neem (Azadirachta indica
) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3. Asian Pac J Cancer Prev 2005;6:515-20.
Balasenthil S, Arivazhagan S, Nagini S. Effect of garlic on circulatory oxidant and antioxidant status during 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis. Nutr Res 2000;20:1581-9.
Khafif A, Schantz SP, al-Rawi M, Edelstein D, Sacks PG. Green tea regulates cell cycle progression in oral leukoplakia. Head Neck 1998;20:528-34.
Nagini S, Manoharan S. Biomonitoring the chemopreventive potential of the plant products neem and turmeric in 4-nitroquinoline 1-oxide-induced oral carcinogenesis. J Clin Biochem Nutr 1997;23:33-40.
Makita H, Tanaka T, Fujitsuka H, Tatematsu N, Satoh K, Hara A, et al.
Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin. Cancer Res 1996;56:4904-9.
Mathew B, Sankaranarayanan R, Nair PP, Varghese C, Somanathan T, Amma BP, et al.
Evaluation of chemoprevention of oral cancer with Spirulina fusiformis
. Nutr Cancer 1995;24:197-202.
Garewal H. Chemoprevention of oral cancer: Beta-carotene and Vitamin E in leukoplakia. Eur J Cancer Prev 1994;3:101-7.
Azuine MA, Bhide SV. Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice. Nutr Cancer 1992;17:77-83.
Sugunadevi G, Suresh K, Vijayaanand MA, Rajalingam K, Sathiyapriya J. Anti genotoxic effect of Mosinone-A on 7,12-dimethylbenz[a] anthracene induced genotoxicity in male golden Syrian hamsters. Pathol Oncol Res 2012;18:69-77.
Baskaran N, Rajasekaran D, Manoharan S. Coumarin protects 7,12-dimethylbenz(a)anthracene-induced genotoxicity in the bone marrow cells of golden Syrian hamsters. Int J Nutr Pharmacol Neurol Dis 2011;1:167-73.
Manoharan S, Singh AK, Suresh K, Silvan S, Baskaran N, Prabhakar MM, et al
. Protective efficacy of andrographolide on 7,12-dimethylbenz(a)anthracene induced genotoxicity in bone marrow cells of golden Syrian hamsters. J Cell Tissue Res 2011;11:2751-8.
Sindhu G, Manoharan S. Anti-clastogenic effect of berberine against DMBA-induced clastogenesis. Basic Clin Pharmacol Toxicol 2010;107:818-24.
Balakrishnan S, Menon VP, Manoharan S, Rajalingam K. Antigenotoxic effect of ferulic acid in 7,12-dimethyl benz(a)-anthracene (DMBA) induced genotoxicity. Afr J Tradit Complement Altern Med 2007;5:32-8.
Mohan KV, Letchoumy PV, Hara Y, Nagini S. Combination chemoprevention of hamster buccal pouch carcinogenesis by bovine milk lactoferrin and black tea polyphenols. Cancer Invest 2008;26:193-201.
Wang WH, Tyan YC, Chen ZS, Lin CG, Yang MH, Yuan SS, et al.
Evaluation of the antioxidant activity and antiproliferative effect of the jaboticaba (Myrciaria cauliflora
) seed extracts in oral carcinoma cells. Biomed Res Int 2014;2014:185946.
Manoharan S, Sindhu G, Vinothkumar V, Kowsalya R. Berberine prevents 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis: A biochemical approach. Eur J Cancer Prev 2012;21:182-92.
Silvan S, Manoharan S, Baskaran N, Anusuya C, Karthikeyan S, Prabhakar MM. Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Eur J Pharmacol 2011;670:571-7.
Sithranga Boopathy N, Kandasamy K, Subramanian M, You-Jin J. Effect of mangrove tea extract from Ceriops decandra
(Griff.) Ding Hou. on salivary bacterial flora of DMBA induced hamster buccal pouch carcinoma. Indian J Microbiol 2011;51:338-44.
Kowsalya R, Vishwanathan P, Manoharan S. Chemopreventive potential of 18 beta-glycyrrhetinic acid: An active constituent of liquorice, in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Pak J Biol Sci 2011;14:619-26.
Vinothkumar V, Manoharan S. Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Redox Rep 2011;16:91-100.
Thanusu J, Kanagarajan V, Nagini S, Gopalakrishnan M. Chemopreventive potential of 3-[2,6-bis(4-fluorophenyl)- 3-methylpiperidin-4-ylideneamino]-2- thioxoimidazolidin- 4-one on 7,12-dimethylbenz[a] anthracene (DMBA) induced hamster buccal pouch carcinogenesis. J Enzyme Inhib Med Chem 2010;25:836-43.
Suresh K, Manoharan S, Vijayaanand MA, Sugunadevi G. Chemopreventive and antioxidant efficacy of (6)-paradol in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Pharmacol Rep 2010;62:1178-85.
Priyadarsini RV, Manikandan P, Kumar GH, Nagini S. The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radic Res 2009;43:492-504.
Manoharan S, Balakrishnan S, Menon VP, Alias LM, Reena AR. Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med J 2009;50:139-46.
Manoharan S, Panjamurthy K, Balakrishnan S, Vasudevan K, Vellaichamy L. Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis. Pharmacol Rep 2009;61:719-26.
Srinivasan P, Suchalatha S, Babu PV, Devi RS, Narayan S, Sabitha KE, et al.
Chemopreventive and therapeutic modulation of green tea polyphenols on drug metabolizing enzymes in 4-nitroquinoline 1-oxide induced oral cancer. Chem Biol Interact 2008;172:224-34.
Vidjaya Letchoumy P, Chandra Mohan KV, Stegeman JJ, Gelboin HV, Hara Y, Nagini S. Pretreatment with black tea polyphenols modulates xenobiotic-metabolizing enzymes in an experimental oral carcinogenesis model. Oncol Res 2008;17:75-85.
Chandra Mohan KV, Subapriya R, Hara Y, Nagini S. Enhancement of erythrocyte antioxidants by green and black tea polyphenols during 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. J Med Food 2006;9:373-7.
Bharti V, Gupta UD, Das SN. Plumbago zeylanica
extract inhibits cyclin D1, NF-kB and induces apoptosis in oral cancer cells. J Pharm Res 2015;9:264-70.
Lee RH, Shin JC, Kim KH, Choi YH, Chae JI, Shim JH. Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1. Oncol Rep 2015;33:631-8.
Wang LJ, Zhou X, Wang W, Tang F, Qi CL, Yang X, et al.
Andrographolide inhibits oral squamous cell carcinogenesis through NF-kB inactivation. J Dent Res 2011;90:1246-52.
Yu FS, Yang JS, Yu CS, Lu CC, Chiang JH, Lin CW, et al.
Safrole induces apoptosis in human oral cancer HSC-3 cells. J Dent Res 2011;90:168-74.
Harish Kumar G, Vidya Priyadarsini R, Vinothini G, Vidjaya Letchoumy P, Nagini S. The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis. Invest New Drugs 2010;28:392-401.
Berta GN, Salamone P, Sprio AE, Di Scipio F, Marinos LM, Sapino S, et al.
Chemoprevention of 7,12-dimethylbenz[a] anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-beta-cyclodextrin. Oral Oncol 2010;46:42-8.
Balakrishnan S, Manoharan S, Alias LM, Nirmal MR. Effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Indian J Biochem Biophys 2010;47:7-12.
Li G, Wang Q, Qian Y, Zhao X. Antioxidant, antimutagenic, and in vivo
buccal mucosa cancer preventive effects of fructus malvae. Food Sci Biotechnol 2014;23:1341-8.
Lee HJ, Auh QS, Lee YM, Kang SK, Chang SW, Lee DS, et al.
Growth inhibition and apoptosis-inducing effects of cudraflavone B in human oral cancer cells via MAPK, NF-kB, and SIRT1 signaling pathway. Planta Med 2013;79:1298-306.
Kumar G, Tajpara P, Maru G. Dietary turmeric post-treatment decreases DMBA-induced hamster buccal pouch tumor growth by altering cell proliferation and apoptosis-related markers. J Environ Pathol Toxicol Oncol 2012;31:295-312.
Tsai RL, Ho BY, Pan TM. Red mold rice mitigates oral carcinogenesis in 7,12-Dimethyl-1,2-Benz[a] anthracene-induced oral carcinogenesis in hamster. Evid Based Complement Alternat Med 2011;2011:245209.
Zhu X, Xiong L, Zhang X, Shi N, Zhang Y, Ke J, et al
. Lyophilized strawberries prevent 7,12-dimethylbenz[a] anthracene (DMBA)-induced oral squamous cell carcinogenesis in hamsters. J Funct Food 2015;15:476-86.
Han HY, Kim H, Jeong SH, Lim DS, Ryu MH. Sulfasalazine induces autophagic cell death in oral cancer cells via Akt and ERK pathways. Asian Pac J Cancer Prev 2014;15:6939-44.
Yang JS, Lin CW, Hsieh YS, Cheng HL, Lue KH, Yang SF, et al. Selaginella tamariscina
(Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways. Food Chem Toxicol 2013;59:801-7.
Kuo YY, Lin HP, Huo C, Su LC, Yang J, Hsiao PH, et al.
Caffeic acid phenethyl ester suppresses proliferation and survival of TW2.6 human oral cancer cells via inhibition of Akt signaling. Int J Mol Sci 2013;14:8801-17.
Weng JR, Bai LY, Chiu CF, Wang YC, Tsai MH. The dietary phytochemical 3,3′-diindolylmethane induces G2/M arrest and apoptosis in oral squamous cell carcinoma by modulating Akt-NF-kB, MAPK, and p53 signaling. Chem Biol Interact 2012;195:224-30.
Hseu YC, Lee MS, Wu CR, Cho HJ, Lin KY, Lai GH, et al.
The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway. J Agric Food Chem 2012;60:2385-97.
Kim JY, An JM, Chung WY, Park KK, Hwang JK, Kim du S, et al.
Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis in hamsters. Phytother Res 2013;27:493-8.
Johnson TL, Lai MB, Lai JC, Bhushan A. Inhibition of cell proliferation and MAP kinase and Akt pathways in oral squamous cell carcinoma by genistein and biochanin A. Evid Based Complement Alternat Med 2010;7:351-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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