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Review
Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer
Kamal Niaz1,2,3orcid, Faheem Maqbool1,2,3orcid, Fazlullah Khan1,2,3orcid, Haji Bahadar4orcid, Fatima Ismail Hassan1,2,3orcid, Mohammad Abdollahi1,2,3orcid
Epidemiol Health 2017;39:e2017009.
DOI: https://doi.org/10.4178/epih.e2017009
Published online: March 9, 2017
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  • 125 Scopus

1International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran

2Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

4Institute of Paramedical Sciences, Khyber Medical University, Peshawar, Pakistan

Correspondence: Mohammad Abdollahi Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran E-mail: mohammad.abdollahi@utoronto.ca
• Received: December 16, 2016   • Accepted: March 9, 2017

©2017, Korean Society of Epidemiology

This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.
The term “smokeless tobacco” refers to the consumption of unburned tobacco, in the form of chewing, spitting, dipping, and snuff. Consumers chew the tobacco in the mouth and spit out the juice that builds up. Nicotine and other constituents are absorbed in the lining of oral cavity. People of many regions, including India, Pakistan, other Asian countries, and North America, have a long history of smokeless tobacco use. Approximately 28 chemical constituents present in smokeless tobacco are carcinogenic in nature, among which nitrosamine is the most prominent [1].
People mostly use paan and gutkha due to a lack of awareness and education. They are not aware of the harmful effects associated with the use of these substances, and it has been reported that these products are consumed for perceived beneficial effects, such as mouth freshening, aid in digestion, germ-killing, astringency, mood enhancement, tension relief, and oral cleaning [1]. Gutkha is sweet in taste, and children consider it to be a form of candy. Many people believe that gutkha is a mouth freshener, but its pleasant taste and sweetness aggregate microbes, causing damage to teeth. The use of paan and gutkha is difficult to control in most countries where it is widespread, and their extensive use leads to oral cancer [2]. The consumption of smokeless tobacco and areca nut is high in South Asian countries in the form of paan. In various South Asian languages, paan simply means “leaf.” Various ingredients are wrapped in the betel leaf. The common components of paan are tobacco, seeds, quenched lime, spices, and areca nut enfolded in betel quid [2]. In many developed and developing countries, tobacco is widely used with other constituents, as shown in Table 1. Over three decades ago, a tobacco industry emerged in India producing gutkha, which consists of slaked lime, areca nut, chewing tobacco, spices, and catechu packed in tins or pouches [2].
Oral submucous fibrosis (OSMF) is a persistent disorder of the oral cavity characterized by irritation and progressive fibrosis of the superficial and deep connective tissues. Oral cancer has been commonly observed in India, Pakistan, Sri Lanka, Taiwan, China, Indonesia, and Malaysia [3,4]. It is believed that the pathogenesis of OSMF is multifactorial, and is associated with nutritional deficiencies; the consumption of smokeless areca nuts, chilies, and lime; genetic abnormalities; betel quid; tobacco smoking; herpes simplex virus; human papilloma virus (HPV); chronic candidiasis; and immunological depression [5]. Oral cancer is the sixth most predominant type of cancer worldwide, affecting both genders equally, although it is particularly common in men in developing countries [6].
Smokeless tobacco and areca nut consumption in various forms is part of traditional culture in the US and in South Asian countries. Essentially, areca nut is the fruit derived from Areca catechu. It is produced in a chewable form and is also the main component of various products used daily by the younger population. Areca nut contains tannins (11 to 26%), which act as stimulants, and alkaloids (0.15 to 0.67%), mainly arecoline [2].
Areca nuts are extensively used, and have noxious and stimulant effects. Studies have reported that areca nut leads to diminished hunger, enhanced digestion, altered concentration, and relaxation, and sometimes also increases alertness [2]. The use of gutkha has been shown to have genotoxic and clastogenic properties [1]. In some cases, alcohol plays an important role in oral cancer, rather than smoking [7]. The use of smokeless tobacco products together with alcoholism and smoking increases the chance of oral cancer. In this study, our main focus was on the consumption of paan and gutkha, which are common smokeless products, and their role in the induction of OSMF, which ultimately leads to oral cancer.
A bibliographic search for the current review was conducted on PubMed, Scopus, and Google Scholar for articles on oral cancer due to paan and gutkha consumption. First, a PubMed search was conducted for the following terms: “presence of smokeless tobacco in Taiwan,” “prevalence in India,” “prevalence in Pakistan,” “presence of smokeless in Asia,” “occurrence of paan and gutkha in Tanzania,” “epidemiological prevalence and presence of smokeless tobacco in Indonesia and Malaysia,” “prevalence and presence of paan and gutkha in Cambodia,” and “prevalence of paan and gutkha in migrated peoples.”
Scopus was searched for terms including: “oral cancer due to paan and gutkha,” “genotoxic effect of paan,” “paan and gutkha chewers,” “betel quid compounds,” “risk factor of oral cancer,” “prevalence of oral cancer,” “paan associated with oral cancer,” “smokeless products lead to oral cancer,” and “gutkha usage.” Google Scholar was searched for keywords such as “carcinogenic effect of betel,” “mechanism of oral cancer due to paan and gutkha,” “ban of paan and gutkha,” and “OSMF mechanism and etiopathogenesis.” The data included in this article were filtered to ensure that they were specifically related to human beings and some laboratory animals. Most studies that investigated the toxicity of tobacco in other systems were excluded. Furthermore, articles were excluded if the data on oral cancer were associated with other brain and neck cancers. Studies that focused on single or limited cases with adverse effects but did not show a clear role of smokeless tobacco in the pathogenesis were also excluded. Eventually, a total of 90 reports indexed in Google Scholar and/or PubMed were found to satisfy the inclusion criteria. Studies not indexed in PubMed were obtained by manual searching in Google Scholar, and 10 such reports that satisfied the inclusion criteria were additionally retrieved. Therefore, a total of 100 studies were included in this review (Figure 1).
The habit of chewing areca nut in various products has been reported in many countries, such as Thailand, Sri Lanka, Bangladesh, Pakistan, Malaysia, Cambodia, China, Indonesia and New Guiana. In addition, it is also widespread in the migrant populations in places such as the UK, South and East Africa, Australia, and North America [4]. In New Guiana, people use betel quid separately, with lime kept in the commissure of the mouth [8]. In Southeast Asian countries, tobacco is often used with betel quid, and smoking is also common. Inhabitants of the mountains of Cambodia, Myanmar, Thailand, and Laos add areca to the roots of other local plants, such as cinnamon and cloves, in the betel quid for consumption [9]. Approximately 390,000 cases of oral and/or pharyngeal cancers occur annually worldwide, of which around 58% are in South and Southeast Asian countries [2]. Some countries in which smokeless tobacco is consumed are discussed below.
Taiwan
Traditionally, tobacco has been consumed as part of the culture in some countries of the world. However, in Taiwan, an increase in the consumption of paan, gutkha and other smokeless tobacco products has been reported, especially among children and teenagers. Many epidemiological studies have been conducted in Taiwan, where betel leaves or betel inflorescence is used with areca nut. The prevalence of smokeless tobacco use among men and women is 9.8 and 1.6%, respectively [10]. In 1991, a survey-based study was conducted among the residents of Kaohsiung in Taiwan; among 1,162 individuals aged 15 years and above, 13.3% consumed betel quid and 2.8% were daily chewers [11]. The increase in the usage of betel quid has been investigated in many studies. The phenomenon appears due to the surplus in markets and shops selling ready-made quid. In more than 53% of cases, use of these products started among family members influenced by the grandfather and father [10]. In another school-based survey in Taiwan, the consumption of betel quid was higher, especially among boys rather than girls. It was also common amongst those who used to drink alcohol or smoke tobacco [10,12]. Betel quid use was common in professional schools rather than senior or junior high-school [12,13].
India
According to the National Report of Global Adult Tobacco Survey conducted in India and Bangladesh, the current prevalence of smokeless tobacco use is 25.9 and 27.2%, respectively. There are 30 different types of smokeless products available in these countries, including zarda, which contains dried and boiled tobacco leaves, limes, areca nut, additives, spices, and tannins [14]. Oral cancer accounts for 30 to 40% of cancer cases reported in India, and the most obvious cause is the extensive use of tobacco products, consumed via smoking and/or smokeless chewing products [15]. In addition, oral cancer occurrence is especially high in Uttar Pradesh in north India due to the extraordinary rate of consumption of smokeless tobacco products, such as paan and gutkha [16].
In India, the prevalence of oral cancer is high. It has been previously documented that besides other factors, the extensive use of paan, gutkha, and zarda could also contribute to the development of oral cancer [2]. In India, mostly children and teenagers chew gutkha occasionally or regularly. In Mumbai, 40% of school students and 70% of college students have been reported to regularly consume gutkha. Although some states of India have banned gutkha consumption due to its carcinogenic properties and other hazardous effects, it is still actively sold on the black market [2]. In addition, the widespread habit of paan and gutkha use is not limited to the Indian subcontinent, but extends to immigrants living in US and Europe [17-20]. In the Indian city of Wardha, gutkha was found to be used by approximately 46.4% of men and 20% of women [18].
Pakistan
After India, Pakistan is the second prominent country in which these smokeless tobacco products are consumed, with a prevalence among Pakistani men and women of 21.3 and 19.3%, respectively. More than 90% of oral cancer cases have been reported to be associated with the use of tobacco products, indicating that they are vital factors triggering oral cancer. A study reported that women who chewed tobacco more than 10 times a day had a higher risk of oral cancer than non-tobacco chewers [21]. A study conducted by Muwonge et al. [22] reported that smokeless tobacco users were at a higher risk of oral cancer, along with other abnormalities, than tobacco smokers.
Worldwide, almost 600 million people consume areca nut as part of traditions and/or everyday life. Many epidemiological studies in India and Pakistan have reported that 3.3 to 37.0% of people chewed paan. In Pakistan and India, oral cancer is the most common type of cancer, after breast and lung cancer. Breast cancer is mostly observed among women [23]. The incidence of mouth, tongue, hypopharynx, nasopharynx, and lip cancer was found to be equal between men and women in Karachi, Pakistan [16,24-26].
The use of these products is considered to be a normal cultural practice. paan, gutkha, chaalia, naswar, and toombak are widely used, but ultimately lead to OSMF and oral cancer. Various studies have suggested that in Pakistan, India, and Nepal, 20 to 30% of adults and teenagers use these products [27-29]. In Karachi, Pakistan, 40% of the populations have used chewable betel, areca, and tobacco products in their daily life [30]. The overall prevalence of the use of the above products in men and women was 50.3 and 28.5%, respectively. A study conducted among school children in Karachi, Pakistan, reported that more than 74% of students used chewable products on a daily basis [31]. According to a report in 2006, the general use of paan, chaalia, gutkha, naswar, and toombak was determined to be 34.3, 34.7, 46.0, and 50.0% in the Sindh, Punjab, Pathan, and Mohajir provinces, respectively [19].
The prevalence of paan and gutkha has been reliably documented, although fluctuating results have been reported in investigations of specific communities. A study conducted one decade previously found that 46% of the residents of Karachi, Pakistan consumed gutkha habitually [32]. Similarly, in another study it was found that 35% of the patients visiting a health care center in Karachi, Pakistan, were habitual consumers of paan, gutkha, and/or other smokeless tobacco products [17].
Tanzania
In Tanzania, 7% of the native inhabitants were found to use gutkha on a daily basis [41]. In addition to paan and gutkha, other risk factors were found to be involved in the development of oral cancer, as shown in Table 2 [21,42,43].
Cambodia
In Cambodia, most users add tobacco to quid, and another practice is to rub it into the gum after chewing betel quid. The consumers of smokeless tobacco were mostly elder women [44]. In an epidemiological study, it was reported that 32.6% of women and 0.8% of men above 15 years of age chewed betel quid. Most of the men were approximately 50 years of age, and most of the women chewers were over the age of 39 in that study. Overall, smoking was prevalent in men (43%), but rare in women (4.5%) [45].
In the Pacific island of Palau, areca nut is chewed in a green unripe state, with other spices and flavoring ingredients. A population-based study conducted in 1991 revealed that 80% of women and 70% of men chewed areca nut or betel quid, 80% of whom included tobacco in the betel quid [46].
Indonesia and Malaysia
The use of smokeless tobacco is different in these countries. In Indonesia, first the betel quid is chewed, and finally a fine-cut tobacco is used to clean the teeth, while keeping it in the mouth for a moment [8]. In Malaysia, use of paan and gutkha is high among some native groups, who use betel quid with tobacco.
Usage in migrant communities
The high risk of oral cancer among migrants in the UK is due to the massive consumption of betel quid and other smokeless products. People who have migrated from Pakistan, India, Bangladesh, and Sri Lanka to the UK are the major communities in which betel quid use is widespread [47]. Various studies have found that over 80% of adults from Bangladesh in London used betel quid and other products, with no gender differences. The use of tobacco, in smoking or in smokeless forms, is common among men and women [48,49]. The usage of these products is becoming well known in these communities. Studies conducted on betel quid and tobacco use among South Asian emigrants to Western countries have pointed out the lack of awareness of oral cancer risk regardless of gender, age, national group, and social class. Individuals tend to be more aware of smoking, but not attentive to other habits that pose a risk of oral cancer, such as paan and gutkha.
paan, gutkha, and zarda are taken by mouth, chewed, sucked, or applied to the teeth and gums. The World Health Organization has classified smokeless tobacco products as human carcinogenic compounds, in particular tobacco-specific nitrosamines, which account for 76 to 91% of the total N-nitroso compound (NOC) burden [14]. These products have been associated with oral and pancreatic cancers, cardiovascular disease, periodontal disease, asthma, and deformities in the women reproductive system [1]. The mechanisms of paan and gutkha that have been proposed for humans are summarized in Figure 2 [42,43]. Studies have shown that tobacco users who include slaked lime in betel quid or with areca nut experience carcinogenic and genotoxic effects in human oral epithelium cells. These products generate reactive oxygen species (ROS) in the oral cavity of chewers [50]. A study conducted in India reported that the greatest extent of DNA disruption was observed in gutkha consumers who smoked, with the following order of the extent of DNA denaturation: gutkha+smoking>paan+ smoking>gutkha only>paan only> smoking only> no tobacco use [51].
The different ingredients used in paan and gutkha have their own detrimental effects, such as catechu, which consists of tannin and polyphenols, which have a high tendency to cause esophageal cancer and are characterized by mutagenicity and clastogenicity [52-54]. The lime (calcium hydroxide) used can result in an alkaline pH, triggering ROS release and causing irritation of the oral mucosa and hyperplasia [55]. Areca nut consists of phenolic compounds, and tobacco releases various nitrosamines in the mouth that are responsible for proliferative abrasions and damage to DNA and fibroblasts [42,56].
A Mexican study conducted in 2006 indicated that single-cell gel electrophoresis is a safe method of determining DNA damage in human populations [57]. When the amount of ROS production in cells is increased in the presence of a normal detoxification system, oxidative stress leads to cellular damage, along with DNA damage [58]. DNA destruction may occur in the form of doublestrand or single-strand DNA breaks [59]. Areca nut is the main component of paan and gutkha, while the areca nut used in gutkha leads to OSMF [60]. The incidence of micronuclei (MN) was observed among OSMF patients who chewed gutkha [51]. Studies have shown that ROS production triggered OSMF [61]. NOCs extracted from areca nuts, which contain the active substance 3-(methylnitrosamino)proprionitrile, have been found to cause genotoxicity and cytotoxicity responsible for tumors in the buccal cavity of smokeless tobacco consumers [62]. The long-lasting and frequent presence of paan and gutkha in the mouth around the gums leads to inflammation of the oral mucosa, which causes the activation of T-cells and macrophages, and ultimately the release of prostaglandins (PGs). PG production occurs in keratinocytes of the buccal cavity due to areca nut extract, and this plays a significant role in oral tissue fibrosis and cancer. Cytokines such as interferon-α, tumor necrosis factor (TNF), interleukin-6, and growth factor-like transforming growth factor-beta have been found to be produced at the sites of irritation [63]. These chemical substances make important contributions to OSMF and premalignancy (Figure 3) [53,63].
Genotoxic effects occur from paan and gutkha mostly due to the presence of nitrosamine, as shown in Table 3. The nitrosamine in the chewers’ saliva undergoes nitration during betel quid chewing when it reacts with nitrite in the presence of a catalyst [42,64]. The nitrosamine in tobacco undergoes metabolic activation by cytochrome P450 enzymes, which may lead to the formation of N-nitrosonornicotine, a major carcinogen [65], which further leads to DNA damage and ultimately oral cancer. MN are small chromatin bodies that appear during cell division in the cytoplasm due to the condensation of whole chromosomes or acrocentric chromosomes; this is the only biomarker used to identify genotoxicity during sister chromatid exchange and chromosomal aberrations [66]. Multiple genes are involved in the breakdown of carcinogens, and the most frequently observed evidence has suggested that cytochrome polymorphisms (CYPs) affect the risk of oral cancer. Arecaidine, arecoline, and other similar ingredients of betel quid exist in minute quantities in human blood, and arecoline levels have been associated with the use of betel quid [67]. We have summarized the effects of CYPs, which are connected with the chewing of betel quid and lead to cancer of the oral cavity and pharynx, in Figure 4 [90,91]. Among the CYPs, CYP1A1 and CYP2E1 may trigger nitrosamines, which ultimately affect the mouth, potentially leading to malignant disorders [91]. In particular, μ-glutathione-stransferase was found to enhance TNF-α. Meanwhile, MN have been used for decades as a biomarker of genotoxic effects. The prolonged use of chewing or masticatory products such as supari, paan, and gutkha can lead to the development of different types of oral cancer. It is therefore necessary to evaluate the population at high risk due to using these products at high doses on a daily basis. paan and gutkha have been found to have carcinogenic effects in laboratory animals, causing tumors in various organs, such as the liver, mouth, pharynx, and larynx. paan acts as a cancer-promoting agent in mice [92]. A study was conducted in which mice that were fed with paan or gutkha exhibited tumors in the testes, ovary, liver, kidney, stomach, and lung. This suggests that gutkha and paan are not only carcinogenic for the oral cavity, but may also exert deleterious effects on other organs [93].
Studies have shown that paan and gutkha comprise trace elements, such as magnesium, chlorine, calcium, sodium, manganese, copper, bromine, and vanadium. The copper content in these two products is more than other nuts consumed. The average content of copper in these processed products existing in betel nuts was 18± 9 µg/g, which is sufficient to exert deleterious effects on human health. According to the Indian Food Report, this concentration was 2.5 times greater than in raw betel nuts. The cellular metabolism of betel nuts and quid leads to the production of ROS, such as hydrogen peroxide and superoxide anion radicals, at a pH of more than 9.5 [43]. Saliva has the potential to inhibit the production of these ROS and other free radicals from the constituents of betel quid. Nonetheless, hydrogen peroxide and oxygen production occurs due to the alkaline pH that arises from the addition of slaked lime when chewing these products [73,94].
It seems that there is an association between oral inflammatory conditions and the age of individuals who use smokeless tobacco products [95]. However, paan and gutkha may also expose the consumers to other oral mucosal disorders at any stage of life. Javed et al. [32] reported that gutkha chewers 45-65 years of age had more periodontal inflammation. A study that investigated the effects of smokeless tobacco on blood flow response showed that tobacco significantly increased gingival blood flow, arterial blood pressure, and heart rate [96]. In addition, paan and gutkha chewers also have been found to exhibit reduced salivation and mucus formation, thereby reducing the normal microflora of the oral cavity and exposing the mouth to pathogens such as Aspergillus species [97]. For this reason, reduced salivation may also permit pathogens to accumulate in the supragingival and subgingival areas, thus increasing periodontal inflammation in gutkha chewers compared to non-chewers [98].
OSMF was an infrequent disease/condition during the 1960s and 1970s, with a prevalence in older individuals of approximately 0.1-0.5%. Subsequently, in the Indian subcontinent, the consumption of areca nut mixtures in products such as paan and gutkha has led to an epidemic of OSMF in adolescents [99,100]. Case-control studies in New Delhi, Maharashtra, Gujarat, Nagpur, and Bhavnagar have reported that more than 70% of cases of OSMF occurred in people under 35 years of age [2,69,99,100]. paan and gutkha chewers develop this condition more frequently than betel quid chewers. The incidence of OSMF is 75% after 4.5 and 9.5 years of use of paan and betel quid, respectively. The lack of betel quid leaf in paan and the higher levels of areca nuts may facilitate the development of OSMF in paan and gutkha users [21].
Areca nuts mixed with tobacco are not an etiological agent contributing to the development of submucous fibrosis. However, it is thought that the high occurrence of OSMF is due to its effect of enhancing addiction, leading to greater exposure to areca nut chewing. In a range of studies, OSMF was recognized as an extremely hazardous precancerous state. In a cohort study, 12,212 tobacco consumers with OSMF were at a higher risk of malignant transformation than tobacco users without any precancerous lesions [61,69,99]. Sufficient evidence has emerged that betel quid with tobacco, tobacco consumed by chewing with lime, betel quid with or without tobacco, and areca nuts are human carcinogens [69,73]. The use of these products has reached such a proportion that the government has no choice but to ban these products. In public health, banning such extensively used products is difficult and not ideal. In particular, betel quid should be banned, as paan and gutkha are items containing betel quid. The Central Committee of Food Safety of India has issued letters to the central government in support of a ban of betel quid, areca nut, paan, and gutkha.
The reasons for which the Central Committee of Food Safety consistently wants to ban the manufacturing and marketing of these products include: 1) adolescents and teenagers are becoming more addicted; 2) consumers develop OSMF, a precancerous condition, and cancer more quickly than smokers; and 3) women prefer smokeless tobacco due to the social disapproval of smoking and thereby become addicted to gutkha. Thus, in India, all legal evaluation processes necessary to ban gutkha nationally have been accomplished, but it continues to be manufactured and marketed in the black market and/or legally.
In the following states of India, gutkha and paan have been banned: Andhra Pradesh, Goa, Maharashtra (August 1, 2002), and Tamil Nadu (November 19, 2001). Certainly, gutkha producers are on the defensive [20]. Gutkha and paan producers have stated that these regulations were not catastrophic, as these products remain legal in the UK and Singapore, according to the Times of India. Thus, they continue to export paan and gutkha to the UK, Singapore [18,20], Middle East, Japan, and Australia, as well as across South Asia.
In the present study, it was concluded that the extensive use of smokeless tobacco in different forms leads to OSMF, which potentially transforms into a malignant condition in all age groups. The genotoxic and carcinogenic effects of smokeless tobacco in the oral cavity are due to the production of ROS and free radicals. These free radicals and ROS damage the normal DNA and RNA, leading to genotoxicity and, eventually, oral cancer. Previously described mechanisms explain the induction, maintenance, and progression of OSMF due to paan and gutkha. Strict cessation of smokeless tobacco use and follow-up should be implemented to reduce the incidence of oral cancer. Widespread use of these and other products by children, as well as adolescents, is mostly due to their pleasant taste, low cost, and easy availability. Oral cancer rates are increasing due to use of these smokeless tobacco products, in particular among the lower socioeconomic levels that constitute the large majority of the population. It is therefore important to establish appropriate data management, monitoring, and evaluation systems. In addition, oral cancer control policies should be implemented to change the lifestyle and behavior of high-risk populations.
The authors wish to thank the Iran National Science Foundation (INSF).

The authors have no conflicts of interest to declare for this study.

Figure 1.
Flow diagram of the included studies. The flow chart presents the number of citations and resources that were screened, excluded, and/or included in the review.
epih-39-e2017009f1.gif
Figure 2.
Roles of paan and gutkha in oral submucous fibrosis [42,43]. ROS, reactive oxygen species.
epih-39-e2017009f2.gif
Figure 3.
Initial events in the pathogenesis of mouth cancer [56,63]. IL-6, interleukin-6; If-α, interferon-alpha; TNF, tumor necrosis factor; TGF-β, transforming growth factor-beta.
epih-39-e2017009f3.gif
Figure 4.
Molecular mechanism of gutkha [90,91]. CYP, cytochrome polymorphism; GST-μ, μ-glutathione-s-transferase; TNF, tumor necrosis factor.
epih-39-e2017009f4.gif
Table 1.
Some common forms of oral smokeless tobacco and their constituents
Common/native name Ingredients Countries/populations
Toombak Sodium carbonate and tobacco Sudan
Shammah Tobacco, slaked lime, and ash Saudi Arabia
Naswar Tobacco, slaked lime, indigo, cardamom, oil, and menthol Iran, Afghanistan, Pakistan, Central Asia
Nass Tobacco, ash, cotton, and sesame oil Iran, Afghanistan, Pakistan, Central Asia
Mawa Areca nut, lime, and tobacco India
Gadakhu Tobacco and molasses Central India
Zarda Boiled tobacco India and Arab countries
Paan/betel quid Areca nut, betel leaf, slaked lime, spice, and catechu, with or without tobacco Indian subcontinent, New Guinea, Southeast Asia, and South America
Mishri Burned tobacco India
Table 2.
Summary of the risk factors for oral cancer in various Asian countries
Country Associated risk factors Study design No. of subjects Reference
Taiwan Quid without tobacco, smoking, alcohol, heavy metals, HPV, SEC Questionnaire-based 4906 [12]
Vietnam Quid with tobacco Visitors to cancer centers and institute of odontology, relevant publications in Vietnamese, interviews with betel quid vendors and individual betel quid users _ [33]
Pakistan Paan, gutkha, SEC, smokeless tobacco, bidi and cigarette smoking Structured questionnaires 425 [19]
Sri Lanka Betel quid, tobacco Cross-sectional community-based study 1,029 [34]
Yemen Cigarette smoking, smokeless tobacco, quid with tobacco History-based study 649 [35]
India Quid with or without tobacco, smokeless tobacco, alcohol, bidi and cigarette smoking, HPV, diet, SEC Nested case-control design 1,692 [22]
Philippines Quid, smoking Case-control study 566 [36]
Thailand Family history of cancer, alcohol, smoking, quid with tobacco Case-control study 104 [37]
Malaysia Malnutrition, HPV Research analysis of frozen samples of oral tissue 210 [38]
Nepal Bidi Epidemiological study Population aged more than 15 yr [39]
Turkey Malnutrition, alcohol, cigarette smoking, SEC Case-control study 140 [40]

HPV, human papillomavirus; SEC, socioeconomic conditions.

Table 3.
Studies of the genotoxicity of paan and gutkha
Study Source Endpoints
Paan/gutkha [67] BC MN
Tobacco [68] EOMC MN
Betel quid, areca, and tobacco [69] BC and PBL CA and MN
Tobacco [70] EBC and PBL MN and CA
Paan [71] CC CA, SCE, and MN
Paan/betel quid [72] TRP QBT
Lime [73] EOMC CT and MN
Slaked lime [74] PMB HE
Areca nut [75] STS Mutagenicity
Areca nut [76] HBEC CFFA, NRA, TRA
Paan [77] Ovary cells SCE and CA
Tobacco products [78] ME, CTLE Ames assay
Catechu [79] Liver tissue Ames assay
Arecoline [80] BMC SCE
Paan [81] Mice SCE
Paan [82] PBL SCE, CA, and MN
Paan, tobacco [83] HOK NHOKs
Paan [84] BPL MN, CA, and SCE
Tobacco [85] VTF DTT
Paan [86] Mice MA
Betel quid/paan [72] TRP QBT
Tobacco [87] SNT DTT
Gutkha/paan [88] BMC MN
Tobacco, areca nuts, and betel leaf [69] PBL and BC MN and CA
Tobacco [70] PBL and EBC CA and MN
Paan [89] Rats MEA

SCE, sister chromatid exchange; CA, chromosomal aberrations; STS, Salmonella typhimurium strains; PMB, popular band of paan; TRP, tobacco and its related products; CC, cultured cells; EBC, exfoliated buccal mucosal cells; PBL, peripheral blood lymphocytes; BC, buccal cells; MN, micronuclei; QBT, questionnaire about betel quid type; HBEC, human buccal epithelial cells; BMC, bone marrow cells; EOMC, exfoliated oral mucosal cells; ME, extract of masher; HOK, human oral keratinocytes; SNT, smoking and non-smoking forms of tobacco; CTLE, chewing tobacco and lime; MA, morphological abnormalities; NHOKs, normal human oral keratinocytes; CT, chemiluminescence technique; HE, histological examination; CFFA, colony-forming efficiency assay; VTF, various tobacco forms; NRA, neutral red uptake assay; TRA, trypan blue exclusion assay; MEA, marker of enzyme activities.

  • 1. Banerjee SC, Ostroff JS, Bari S, D’Agostino TA, Khera M, Acharya S, et al. Gutka and Tambaku paan use among South Asian immigrants: a focus group study. J Immigr Minor Health 2014;16:531-539.ArticlePubMedPMC
  • 2. Shah G, Chaturvedi P, Vaishampayan S. Arecanut as an emerging etiology of oral cancers in India. Indian J Med Paediatr Oncol 2012;33:71-79.ArticlePubMedPMC
  • 3. Gupta PC, Warnakulasuriya S. Global epidemiology of areca nut usage. Addict Biol 2002;7:77-83.ArticlePubMed
  • 4. Pillai R, Balaram P, Reddiar KS. Pathogenesis of oral submucous fibrosis. Relationship to risk factors associated with oral cancer. Cancer 1992;69:2011-2020.ArticlePubMed
  • 5. Johnson N. Tobacco use and oral cancer: a global perspective. J Dent Educ 2001;65:328-339.ArticlePubMed
  • 6. Changrani J, Gany F. Paan and Gutka in the United States: an emerging threat. J Immigr Health 2005;7:103-108.ArticlePubMed
  • 7. Thomas G, Hashibe M, Jacob BJ, Ramadas K, Mathew B, Sankaranarayanan R, et al. Risk factors for multiple oral premalignant lesions. Int J Cancer 2003;107:285-291.ArticlePubMed
  • 8. Murti PR. Global aspects of tobacco use and its implications for oral health. In: Gupta PC, Hammer JE, Murti RR, eds. Control of tobacco-related cancers and other disease. Proceedings of an International Symposium. 1990 Jan 15-19. Bombay. Bombay: Oxford University Press. 1992. 13-23.
  • 9. Awang M. Areca catechu (betel) nut and oral submucous fibrosis [dissertation]. London: University of London; 1983.
  • 10. Lu CT, Lan SJ, Hsieh CC, Yang MJ, Ko YC, Tsai CC, et al. Prevalence and characteristics of areca nut chewers among junior high school students in Changhua county, Taiwan. Community Dent Oral Epidemiol 1993;21:370-373.ArticlePubMed
  • 11. Chen JW, Shaw JH. A study on betel quid chewing behavior among Kaohsiung residents aged 15 years and above. J Oral Pathol Med 1996;25:140-143.ArticlePubMed
  • 12. Yang MS, Su IH, Wen JK, Ko YC. Prevalence and related risk factors of betel quid chewing by adolescent students in southern Taiwan. J Oral Pathol Med 1996;25:69-71.ArticlePubMed
  • 13. Ho CS, Gee MJ, Tsai CC, Lo CI, Wang SC. The prevalence of betel chewing among the students of the different senior high schools in southern Taiwan. Kaohsiung J Med Sci 2000;16:32-38.PubMed
  • 14. Tricker AR, Preussmann R. The occurrence of N-nitrosocompounds [corrected] in zarda tobacco. Cancer Lett 1988;42:113-118.ArticlePubMed
  • 15. Ali SM, Qureshi R, Jamal S. Prevalence of oral submucous fibrosis and use of tobacco and related products amongst school going males. Pak Oral Dent J 2011;31:384-387.
  • 16. Mehrotra R, Singh M, Gupta RK, Singh M, Kapoor AK. Trends of prevalence and pathological spectrum of head and neck cancers in North India. Indian J Cancer 2005;42:89-93.ArticlePubMed
  • 17. Ali NS, Khuwaja AK, Ali T, Hameed R. Smokeless tobacco use among adult patients who visited family practice clinics in Karachi, Pakistan. J Oral Pathol Med 2009;38:416-421.ArticlePubMed
  • 18. Dongre A, Deshmukh P, Murali N, Garg B. Tobacco consumption among adolescents in rural Wardha: where and how tobacco control should focus its attention? Indian J Cancer 2008;45:100-106.ArticlePubMed
  • 19. Mazahir S, Malik R, Maqsood M, Merchant KA, Malik F, Majeed A, et al. Socio-demographic correlates of betel, areca and smokeless tobacco use as a high risk behavior for head and neck cancers in a squatter settlement of Karachi, Pakistan. Subst Abuse Treat Prev Policy 2006;1:10.ArticlePubMedPMC
  • 20. Changrani J, Gany FM, Cruz G, Kerr R, Katz R. Paan and gutka use in the United States: a pilot study in Bangladeshi and IndianGujarati immigrants in New York City. J Immigr Refug Stud 2006;4:99-110.ArticlePubMedPMC
  • 21. 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;14:5567-5577.ArticlePubMedPDF
  • 22. 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;44:446-454.ArticlePubMed
  • 23. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-2917.ArticlePubMed
  • 24. Curado MP; International Agency for Research on Cancer (IARC); World Health Organization. Cancer incidence in five continents. Vol. IX. Lyon: IARC; 2007. p 258.
  • 25. Bhurgri Y, Bhurgri A, Hassan SH, Zaidi SH, Rahim A, Sankaranarayanan R, et al. Cancer incidence in Karachi, Pakistan: first results from Karachi Cancer Registry. Int J Cancer 2000;85:325-329.ArticlePubMed
  • 26. Bhurgri Y. Cancer of the oral cavity - trends in Karachi South (1995-2002). Asian Pac J Cancer Prev 2005;6:22-26.PubMed
  • 27. Gupta PC, Ray CS. Epidemiology of betel quid usage. Ann Acad Med Singapore 2004;33:31-36.ArticlePubMed
  • 28. Qidwai W, Saleheen D, Saleem S, Andrades M, Azam SI. Are our people health conscious? Results of a patients survey in Karachi, Pakistan. J Ayub Med Coll Abbottabad 2003;15:10-13.
  • 29. Mahmood Z. Smoking and chewing habits of people of Karachi-- 1981. J Pak Med Assoc 1982;32:34-37.PubMed
  • 30. Khawaja MR, Mazahir S, Majeed A, Malik F, Merchant KA, Maqsood M, et al. Knowledge, attitude and practices of a Karachi slum population regarding the role of products of betel, areca and smokeless tobacco in the etiology of head & neck cancers. J Pak Med Assoc 2005;55:S41.
  • 31. Shah SM, Merchant AT, Luby SP, Chotani RA. Addicted schoolchildren: prevalence and characteristics of areca nut chewers among primary school children in Karachi, Pakistan. J Paediatr Child Health 2002;38:507-510.ArticlePubMed
  • 32. Javed F, Altamash M, Klinge B, Engström PE. Periodontal conditions and oral symptoms in gutka-chewers with and without type 2 diabetes. Acta Odontol Scand 2008;66:268-273.ArticlePubMed
  • 33. Reichart PA, Nguyen XH. Betel quid chewing, oral cancer and other oral mucosal diseases in Vietnam: a review. J Oral Pathol Med 2008;37:511-514.ArticlePubMed
  • 34. Amarasinghe HK, Usgodaarachchi US, Johnson NW, Lalloo R, Warnakulasuriya S. Betel-quid chewing with or without tobacco is a major risk factor for oral potentially malignant disorders in Sri Lanka: a case-control study. Oral Oncol 2010;46:297-301.ArticlePubMed
  • 35. Sawair FA, Al-Mutwakel A, Al-Eryani K, Al-Surhy A, Maruyama S, Cheng J, et al. High relative frequency of oral squamous cell carcinoma in Yemen: qat and tobacco chewing as its aetiological background. Int J Environ Health Res 2007;17:185-195.ArticlePubMed
  • 36. Ngelangel CA, Javelosa MA, Cutiongco-de la Paz EM; Philippine Cancer Genetics Study Group. Epidemiological risk factors for cancers of the lung, breast, colon-rectum & oral cavity: a casecontrol study in the Philippines. Acta Med Philipp 2009;43:29-34.ArticlePDF
  • 37. Loyha K, Vatanasapt P, Promthet S, Parkin DM. Risk factors for oral cancer in northeast Thailand. Asian Pac J Cancer Prev 2012;13:5087-5090.ArticlePubMedPDF
  • 38. Saini R, Tang TH, Zain RB, Cheong SC, Musa KI, Saini D, et al. Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia. J Cancer Res Clin Oncol 2011;137:311-320.ArticlePubMed
  • 39. Karki YB, Pant KD, Pande BR. A study on the economics of tobacco in Nepal; 2003 [cited 2017 Mar 25]. Available from: https://escholarship.org/uc/item/7zj8q2dj#page-1.
  • 40. Güneri P, Cankaya H, Yavuzer A, Güneri EA, Erişen 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;41:1005-1012.ArticlePubMed
  • 41. Kaduri P, Kitua H, Mbatia J, Kitua AY, Mbwambo J. Smokeless tobacco use among adolescents in Ilala Municipality, Tanzania. Tanzan J Health Res 2008;10:28-33.PubMed
  • 42. Nair J, Ohshima H, Friesen M, Croisy A, Bhide SV, Bartsch H. Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis 1985;6:295-303.ArticlePubMedPDF
  • 43. Nair UJ, Floyd RA, Nair J, Bussachini V, Friesen M, Bartsch H. Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact 1987;63:157-169.ArticlePubMed
  • 44. Reichart PA, Schmidtberg W, Scheifele C. Betel chewer’s mucosa in elderly Cambodian women. J Oral Pathol Med 1996;25:367-370.ArticlePubMed
  • 45. Ikeda N, Handa Y, Khim SP, Durward C, Axéll T, Mizuno T, et al. Prevalence study of oral mucosal lesions in a selected Cambodian population. Community Dent Oral Epidemiol 1995;23:49-54.ArticlePubMed
  • 46. Ysaol J, Chilton JI, Callaghan P. A survey of betel nut chewing in Palau. Isla 1996;4:244-255.
  • 47. Warnakulasuriya S. Areca nut use following migration and its consequences. Addict Biol 2002;7:127-132.ArticlePubMed
  • 48. Bedi R, Gilthorpe MS. The prevalence of betel-quid and tobacco chewing among the Bangladeshi community resident in a United Kingdom area of multiple deprivation. Prim Dent Care 1995;2:39-42.PubMed
  • 49. Ahmed S, Rahman A, Hull S. Use of betel quid and cigarettes among Bangladeshi patients in an inner-city practice: prevalence and knowledge of health effects. Br J Gen Pract 1997;47:431-434.PubMedPMC
  • 50. Babu S, Sesikeran B, Bhat RV. Oral fibrosis among teenagers chewing tobacco, areca nut, and pan masala. Lancet 1996;348:692.Article
  • 51. Jyoti S, Khan S, Afzal M, Naz F, Siddique YH. Evaluation of micronucleus frequency by acridine orange fluorescent staining in bucccal epithelial cells of oral submucosus fibrosis (OSMF) patients. Egypt J Med Human Genet 2013;14:189-193.Article
  • 52. Morton JF. Further associations of plant tannins and human cancer. Q J Crude Drug Res 1972;12:1829-1841.Article
  • 53. Stich HF, Stich W. Chromosome-damaging activity of saliva of betel nut and tobacco chewers. Cancer Lett 1982;15:193-202.ArticlePubMed
  • 54. Giri AK, Banerjee TS, Talukder G, Sharma A. Induction of sister chromatid exchange and dominant lethal mutation by ‘Katha’ (catechu) in male mice. Cancer Lett 1988;38:357-364.ArticlePubMed
  • 55. Dunham LJ, Sheets RH, Morton JF. Proliferative lesions in cheek pouch and esophagus of hamsters treated with plants from Curacao, Netherland Antilles. J Natl Cancer Inst 1974;53:1259-1269.ArticlePubMedPDF
  • 56. Bhide SV, Gothoskar SV, Shivapurkar NM. Arecoline tumorigenicity in Swiss strain mice on normal and vitamin B deficient diet. J Cancer Res Clin Oncol 1984;107:169-171.ArticlePubMed
  • 57. Rojas E, Valverde M, Sordo M, Ostrosky-Wegman P. DNA damage in exfoliated buccal cells of smokers assessed by the single cell gel electrophoresis assay. Mutat Res 1996;370:115-120.ArticlePubMed
  • 58. Speit G, Witton-Davies T, Heepchantree W, Trenz K, Hoffmann H. Investigations on the effect of cigarette smoking in the comet assay. Mutat Res 2003;542:33-42.ArticlePubMed
  • 59. Katyal S, McKinnon PJ. DNA strand breaks, neurodegeneration and aging in the brain. Mech Ageing Dev 2008;129:483-491.ArticlePubMed
  • 60. Jyoti S, Khan S, Afzal M, Siddique YH. Micronucleus investigation in human buccal epithelial cells of gutkha users. Adv Biomed Res 2012;1:35.ArticlePubMedPMC
  • 61. Jeng JH, Chang MC, Hahn LJ. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol 2001;37:477-492.ArticlePubMed
  • 62. Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ. Interaction of collagen-related genes and susceptibility to betel quidinduced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev 2002;11:646-653.PubMed
  • 63. Kandasamy M, Anisa N, Rahman A, Rajan MA, Prakash A, Lal J. Etiopathogenesis of oral submucous fibrosis: review of literature. J Adv Med Dent Sci Res 2015;3:53-58.
  • 64. Nair J, Nair UJ, Ohshima H, Bhide SV, Bartsch H. Endogenous nitrosation in the oral cavity of chewers while chewing betel quid with or without tobacco. IARC Sci Publ 1987;465-469.PubMed
  • 65. 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;19:251-262.ArticlePubMedPDF
  • 66. Jyoti S, Afzal M, Siddique YH. Genotoxic effects of pan masala and gutkha: a review. World J Zool 2011;6:301-306.
  • 67. Fareed M, Afzal M, Siddique YH. Micronucleus investigation in buccal mucosal cells among pan masala/gutkha chewers and its relevance for oral cancer. Biol Med 2011;3:8-15.
  • 68. Jadhav K, Gupta N, Ahmed MB. Micronuclei: an essential biomarker in oral exfoliated cells for grading of oral squamous cell carcinoma. J Cytol 2011;28:7-12.ArticlePubMedPMC
  • 69. Sudha S, Mythili B, Balachandar V. Mixture of betel leaf, areca nut and tobacco chewing is a risk factor for cytogenetic damage in construction workers from south India. Braz J Oral Sci 2009;8:145-148.
  • 70. Patel BP, Trivedi PJ, Brahmbhatt MM, Shukla SN, Shah PM, Bakshi SR. Micronuclei and chromosomal aberrations in healthy tobacco chewers and controls: a study from Gujarat, India. Arch Oncol 2009;17:7-10.Article
  • 71. Jaju RJ, Patel RK, Bakshi SR, Trivedi AH, Dave BJ, Adhvaryu SG. Chromosome damaging effects of pan masala. Cancer Lett 1992;65:221-226.ArticlePubMed
  • 72. Gandhi G, Kaur R, Sharma S. Chewing pan masala and/or betel quid-fashionable attributes and/or cancer menaces. J Hum Ecol 2005;17:161-166.Article
  • 73. Nair UJ, Obe G, Friesen M, Goldberg MT, Bartsch H. Role of lime in the generation of reactive oxygen species from betel-quid ingredients. Environ Health Perspect 1992;98:203-205.ArticlePubMedPMC
  • 74. Sirsat SM, Kandarkar SV. Histological changes in the oral mucosa of the wistar rat treated with commercial lime (calcium hydroxide)- -an optical and submicroscopic study. Br J Cancer 1968;22:303-315.ArticlePubMedPMCPDF
  • 75. Shirname LP, Menon MM, Nair J, Bhide SV. Correlation of mutagenicity and tumorigenicity of betel quid and its ingredients. Nutr Cancer 1983;5:87-91.ArticlePubMed
  • 76. Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafström RC. Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res 1989;49:5294-5298.PubMed
  • 77. Adhvaryu SG, Dave BJ, Trivedi AH. An in vitro assessment of the genotoxic potential of pan masalas. Indian J Med Res 1989;90:131-134.PubMed
  • 78. Niphadkar MP, Bagwe AN, Bhisey RA. Mutagenic potential of Indian tobacco products. Mutagenesis 1996;11:151-154.ArticlePubMedPDF
  • 79. Nagabhushan M, Maru GB, Amonkar AJ, Nair UJ, Santhanam U, Ammigan N, et al. Catechin as an antimutagen: its mode of action. J Cancer Res Clin Oncol 1988;114:177-182.ArticlePubMed
  • 80. Panigrahi GB, Rao AR. Study of the genotoxicity of the total aqueous extract of betel nut and its tannin. Carcinogenesis 1986;7:37-39.ArticlePubMedPDF
  • 81. Mukherjee A, Chakrabarti J, Chakrabarti A, Banerjee T, Sarma A. Effect of ‘pan masala’ on the germ cells of male mice. Cancer Lett 1991;58:161-165.ArticlePubMed
  • 82. Dave BJ, Trivedi AH, Adhvaryu SG. Cytogenetic studies reveal increased genomic damage among ‘pan masala’ consumers. Mutagenesis 1991;6:159-163.ArticlePubMedPDF
  • 83. Bagchi M, Balmoori J, Bagchi D, Stohs SJ, Chakrabarti J, Das DK. Role of reactive oxygen species in the development of cytotoxicity with various forms of chewing tobacco and pan masala. Toxicology 2002;179:247-255.ArticlePubMed
  • 84. Yadav JS, Chadha P. Genotoxic studies in pan masala chewers: a high cancer risk group. Int J Hum Genet 2002;2:107-112.Article
  • 85. Chadda R, Sengupta S. Tobacco use by Indian adolescents. Tob Induc Dis 2002;1:111-119.ArticlePubMedPMC
  • 86. Kumar S, Nigam SK, Shaikh SA, Saiyed HN. Effect of pan masala on sperm morphology of a mouse. Bull Environ Contam Toxicol 2003;70:1184-1188.ArticlePubMed
  • 87. Singh R, Kour H, Jindal SK, Aggarwal AN, Gupta D, Khan GQ, et al. Global youth tobacco survey: a report from Jammu and Kashmir. JK Sci J Med Educ Res 2008;10:65-69.
  • 88. Siddique YH, Ara G, Beg T, Afzal M. Micronucleus investigation in oral mucosal cells of gutkha/pan masala chewers. Indian Biol 2008;40:1-5.
  • 89. Sarma AB, Chakrabarti J, Chakrabarti A, Banerjee TS, Roy D, Mukherjee D, et al. Evaluation of pan masala for toxic effects on liver and other organs. Food Chem Toxicol 1992;30:161-163.ArticlePubMed
  • 90. Wu IC, Chen PH, Wang CJ, Wu DC, Tsai SM, Chao MR, et al. Quantification of blood betel quid alkaloids and urinary 8-hydroxydeoxyguanosine in humans and their association with betel chewing habits. J Anal Toxicol 2010;34:325-331.ArticlePubMedPDF
  • 91. Lin CY, Pan TS, Ting CC, Liang SS, Huang SH, Liu HY, et al. Cytochrome p450 metabolism of betel quid-derived compounds: implications for the development of prevention strategies for oral and pharyngeal cancers. Scientific World Journal 2013;2013:618032.ArticlePubMedPDF
  • 92. Ramchandani AG, D’Souza AV, Borges AM, Bhisey RA. Evaluation of carcinogenic/co-carcinogenic activity of a common chewing product, pan masala, in mouse skin, stomach and esophagus. Int J Cancer 1998;75:225-232.ArticlePubMed
  • 93. Nigam SK, Kumar A, Sheikh S, Saiyed HN. Toxicological evaluation of pan masala in pure inbred Swiss mice: a preliminary report on long-term exposure study. Curr Sci 2001;80:1306-1309.
  • 94. Stich HF, Anders F. The involvement of reactive oxygen species in oral cancers of betel quid/tobacco chewers. Mutat Res 1989;214:47-61.ArticlePubMed
  • 95. Javed F, Näsström K, Benchimol D, Altamash M, Klinge B, Engström PE. Comparison of periodontal and socioeconomic status between subjects with type 2 diabetes mellitus and non-diabetic controls. J Periodontol 2007;78:2112-2119.ArticlePubMed
  • 96. Mavropoulos A, Aars H, Brodin P. The acute effects of smokeless tobacco (snuff) on gingival blood flow in man. J Periodontal Res 2001;36:221-226.ArticlePubMed
  • 97. Avasn Maruthit Y, Rao RS, Palivela H, Thakre S. Impact of gutkha chewing & smoking on microbial environment of oral cavity: a case study on slum dwellers of selected areas in Visakhapatnam. J Environ Sci Eng 2004;46:268-273.PubMed
  • 98. Tseng YH, Chang KW, Liu CJ, Lin CY, Yang SC, Lin SC. Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells. J Periodontal Res 2008;43:490-499.ArticlePubMed
  • 99. Hazare VK, Goel RR, Gupta PC. Oral submucous fibrosis, areca nut and pan masala use: a case-control study. Natl Med J India 1998;11:299.
  • 100. Gupta PC, Mehta FS, Daftary DK, Pindborg JJ, Bhonsle RB, Jalnawalla PN, et al. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 1980;8:283-333.Article

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      Amanjot Kaur, Neeti Rustagi, Shruti Khatana, P. G. Gigi, Aparna Ganesan, Pravin Kumar, Kirti Chaudhry
      Journal of Maxillofacial and Oral Surgery.2023;[Epub]     CrossRef
    • Evaluation of Risk Factors in Patients with Head and Neck Cancer: A Case Control Study
      Zohreh Dalirsani, Zahra Delavarian, Atessa Pakfetrat, Fateme Akbarzade Mahlabani, Mahboobeh Taherizadeh, Ala Ghazi
      Addiction and Health.2023; 15(1): 1.     CrossRef
    • The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories
      Amanda Ramos da Cunha, Kelly Compton, Rixing Xu, Rashmi Mishra, Mark Thomas Drangsholt, Jose Leopoldo Ferreira Antunes, Alexander R. Kerr, Alistair R. Acheson, Dan Lu, Lindsey E. Wallace, Jonathan M. Kocarnik, Weijia Fu, Frances E. Dean, Alyssa Pennini, H
      JAMA Oncology.2023; 9(10): 1401.     CrossRef
    • Global health trends of human papillomavirus‐associated oral cancer: A review
      Kehinde Kazeem Kanmodi, Jimoh Amzat, Jacob Njideka Nwafor, Lawrence Achilles Nnyanzi
      Public Health Challenges.2023;[Epub]     CrossRef
    • Utility of salivary biomarkers for diagnosis and monitoring the prognosis of nicotine addiction - A systematic review
      S. Shreya, Manoj Annamalai, Vasanti Lagali Jirge, Sneha Sethi
      Journal of Oral Biology and Craniofacial Research.2023; 13(6): 740.     CrossRef
    • Assessment of oral health status amongst the Sevayats of Shree Jagannath Temple, Puri, Odisha: A cross sectional study
      Gunjan Kumar, Samikshya Jena, Payal Dash, Yagnaseni Mandal, Alok Kumar Sethi
      National Journal of Maxillofacial Surgery.2023; 14(3): 460.     CrossRef
    • Comparative analysis of two arecoline‐induced oral submucous fibrosis models
      Shijie Tang, Lanxin Jiang, Ying Zhou, Tong Zhou, Yang Peng, Shuting Zhou, Yuan Yue, Xiaoqiang Xia, Jing Li, Qianming Chen, Yuchen Jiang, Xiaodong Feng
      Oral Diseases.2023;[Epub]     CrossRef
    • Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants
      Rafia Shah, Feriha Fatima Khidri, Yar Muhammad Waryah, Roohi Nigar, Amber Mahmood, Hina Shaikh, Muhammad Qasim Awan, Ikram Din Ujjan, Ali Muhammad Waryah
      BioMetals.2023;[Epub]     CrossRef
    • Awareness of Oral Cancer Among Users of Smokeless Tobacco: A Cross-Sectional Study
      Fahd Alharbi, Hatim Alsaedi, Nader S Alharbi, Rawan Alharbi , Hussain Alharbi, Abdullah Alazmi, Fahad Alghamdi
      Cureus.2023;[Epub]     CrossRef
    • Repercussions of Smokeless Tobacco on Buccal Mucosa: A Community Based Observational Study at a Tertiary Care Centre in Western Rajasthan
      Navneet Agarwal, Mohammed Nadeem Shaikh, Anisha Banu, Paridhi Ahuja
      Indian Journal of Otolaryngology and Head & Neck Surgery.2023;[Epub]     CrossRef
    • Prevalence and Determinants of Substance Use Among Indigenous Tribes in South India: Findings from a Tribal Household Survey
      Anvar Sadath, Kurian Jose, KM Jiji, VT Mercy, G Ragesh, Ella Arensman
      Journal of Racial and Ethnic Health Disparities.2022; 9(1): 356.     CrossRef
    • Evidence of Association of CYP1A1 Expression in Blood Lymphocytes and Clinicopathological Variables in Oral Cancer
      R. D. Singh, K. A. Patel, J. B. Patel, S. J. Pandya, P. S. Patel
      Indian Journal of Clinical Biochemistry.2022; 37(2): 178.     CrossRef
    • Oral cancer risk behaviours of Indian immigrants in Australia: a qualitative study
      Nidhi Saraswat, Neeta Prabhu, Rona Pillay, Bronwyn Everett, Ajesh George
      Australian and New Zealand Journal of Public Health.2022; 46(1): 87.     CrossRef
    • Oral lesions associated with smokeless tobacco users in Saudi Arabia: Single center cross-sectional study
      Nada Binmadi, Louae Harere, Ajwad Mattar, Suad Aljohani, Nada Alhindi, Sarah Ali, Soulafa Almazrooa
      The Saudi Dental Journal.2022; 34(2): 114.     CrossRef
    • A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia
      Jagannath Pal, Yogita Rajput, Shruti Shrivastava, Renuka Gahine, Varsha Mungutwar, Tripti Barardiya, Ankur Chandrakar, Pinaka Pani Ramakrishna, Sovna Shivani Mishra, Hansa Banjara, Vivek Choudhary, Pradeep K. Patra, Masood A. Shammas
      Molecular Oncology.2022; 16(8): 1650.     CrossRef
    • Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents—Does Fibroblast Senescence Play a Role?
      Pangzhen Zhang, Nathaniel Quan En Chua, Simon Dang, Ashleigh Davis, Kah Wee Chong, Stephen S. Prime, Nicola Cirillo
      International Journal of Molecular Sciences.2022; 23(3): 1637.     CrossRef
    • Top 100 most-cited articles on intraoral squamous cell carcinoma and its risk factors: a bibliometric study
      Gilberto Melo, Carolina Simão Flausino, Isadora Koepp Darella, Andressa Fernanda Paza Miguel, Paulo Antônio Martins Júnior, Elena Riet Correa Rivero
      Brazilian Oral Research.2022;[Epub]     CrossRef
    • Association between smokeless tobacco use and cigarette smoking amount by age
      Jin-Won Noh, Min-Hee Kim, Yejin Lee, Young Dae Kwon, Kyoung-Beom Kim, Hae-Jeung Lee, Ki-Bong Yoo
      BMC Public Health.2022;[Epub]     CrossRef
    • Toxic effects of smokeless tobacco on female reproductive health: A review
      C. Laldinsangi
      Current Research in Toxicology.2022; 3: 100066.     CrossRef
    • Smokeless tobacco use and reproductive outcomes among women: a systematic review
      A.G. Radhika, Sutapa B. Neogi, Preetha GS, Sumant Swain, Jaswinder Kaur, Jagdish Kaur
      F1000Research.2022; 10: 1171.     CrossRef
    • Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis
      Nicola Cirillo, Peter Hung Duong, Wee Teng Er, Casey Thao Nhi Do, Manikkuwadura Eranda Harshan De Silva, Yining Dong, Sok Ching Cheong, Elizabeth Fitriana Sari, Michael J. McCullough, Pangzhen Zhang, Stephen S. Prime
      Biomolecules.2022; 12(5): 664.     CrossRef
    • Influence of E-Cigarette and Cannabis Vaping on Orthodontically Induced Tooth Movement and Periodontal Health in Patients Undergoing Orthodontic Therapy
      Dimitrios Michelogiannakis, Irfan Rahman
      International Journal of Environmental Research and Public Health.2022; 19(11): 6518.     CrossRef
    • Knowledge, Attitudes and Practices of Indian Immigrants in Australia towards Oral Cancer and Their Perceived Role of General Practitioners: A Cross-Sectional Study
      Nidhi Saraswat, Bronwyn Everett, Rona Pillay, Neeta Prabhu, Amy Villarosa, Ajesh George
      International Journal of Environmental Research and Public Health.2022; 19(14): 8596.     CrossRef
    • The Burden of Cancer, Government Strategic Policies, and Challenges in Pakistan: A Comprehensive Review
      Anwar Ali, Muhammad Faisal Manzoor, Nazir Ahmad, Rana Muhammad Aadil, Hong Qin, Rabia Siddique, Sakhawat Riaz, Arslan Ahmad, Sameh A. Korma, Waseem Khalid, Liu Aizhong
      Frontiers in Nutrition.2022;[Epub]     CrossRef
    • IMPACT OF COVID-19 PANDEMIC ON HEAD AND NECK CANCER SURGERY IN CENTRAL INDIA
      Nitin Tomar, Ayush Naik, Ramesh Arya, Abhishek Pratap Singh, Preety Jain
      INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH.2022; : 22.     CrossRef
    • Trends in the global burden of oral cancer joint with attributable risk factors: Results from the global burden of disease study 2019
      Shijie Zhu, Faxue Zhang, Gaichan Zhao, Xupeng Zhang, Xiaowei Zhang, Tianzhou Li, Chuanwei Hu, Wei Zhu, Dejia Li
      Oral Oncology.2022; 134: 106189.     CrossRef
    • Impact of ban on commercial smokeless tobacco products among users and vendors in West Bengal and Kerala states, India
      Nirmalya Mukherjee, Radhakrishnan Jayakrishnan, Paramita Bhattacharya, Raju Sarkar, Denny John, Arpita Mitra, Biswajit Pal, Pranay Lal
      Clinical Epidemiology and Global Health.2022; 18: 101160.     CrossRef
    • Oral Cancer Risk Assessment for Different Types of Smokeless Tobacco Products Sold Worldwide: A Review of Reviews and Meta-analyses
      Alpana K. Gupta, Mona Kanaan, Kamran Siddiqi, Dhirendra N. Sinha, Ravi Mehrotra
      Cancer Prevention Research.2022; 15(11): 733.     CrossRef
    • Assessing Long Non-coding RNAs in Tobacco-associated Oral Cancer
      Manish Kumar Mishra, Sachin Gupta, Shivangi, Shelly Sehgal
      Current Cancer Drug Targets.2022; 22(11): 879.     CrossRef
    • Flavor Classification/Categorization and Differential Toxicity of Oral Nicotine Pouches (ONPs) in Oral Gingival Epithelial Cells and Bronchial Epithelial Cells
      Sadiya Shaikh, Wai Tung, Cortney Pang, Joseph Lucas, Dongmei Li, Irfan Rahman
      Toxics.2022; 10(11): 660.     CrossRef
    • Histopathological Findings of Oral Mucosa in Smokeless Tobacco Users: Case Report
      Sintija Miļuna, Ričards Melderis, Māris Sperga, Ingus Skadiņš, Juta Kroiča, Dagnija Rostoka
      The Open Dentistry Journal.2022;[Epub]     CrossRef
    • Recent trends of tobacco use in India
      Akshita Chhabra, Showket Hussain, Shazia Rashid
      Journal of Public Health.2021; 29(1): 27.     CrossRef
    • Chewing tobacco may act as a risk factor for dysplastic transformation of squamous cells in Oral leukoplakia- A cytochemistry based approach
      Sayantan Bhattacharyya, Sudipta Ray, Depanwita Saha, Saunak Mitra Mustafi, Neyaz Alam, Aniruddha Sarkar, Nabendu Murmu
      Pathology - Research and Practice.2021; 218: 153287.     CrossRef
    • Use of Smokeless Tobacco Before Conception and Its Relationship With Maternal and Fetal Outcomes of Pregnancy in Thatta, Pakistan: Findings From Women First Study
      Sumera Aziz Ali, Umber Khan, Farina Abrejo, Brandi Vollmer, Sarah Saleem, K Michael Hambidge, Nancy F Krebs, Jamie E Westcott, Robert L Goldenberg, Elizabeth M McClure, Omrana Pasha
      Nicotine & Tobacco Research.2021; 23(8): 1291.     CrossRef
    • MANAGEMENT OF ORAL SUBMUCOSAL FIBROSIS (OSMF) WITH PANCHGAVYA SHUKTA SHODHAN GANDUSHA AS A DINACHARYA PROCEDURE
      Jaiminikumar Shashank Rasane, Sudeep Menon, Ashutosh B Patankar
      International Ayurvedic Medical Journal.2021; 09(1): 91.     CrossRef
    • Pattern of Tobacco consumption among urban slum population in Jammu region: A cross-sectional study
      Neha Choudhary, Sonika Sangra
      Journal of Family Medicine and Primary Care.2021; 10(3): 1193.     CrossRef
    • Oral cavity: An open horizon for nanopharmaceuticals
      Oanh Oanh Thi Nguyen, Khue Dan Tran, Nhan Thi Ha, Sang Minh Doan, Thi Thanh Hai Dinh, Tuan Hiep Tran
      Journal of Pharmaceutical Investigation.2021; 51(4): 413.     CrossRef
    • Modulator effect of mangiferin on biochemical characterization in 7,12‐dimethylbenz[a]anthracene induced oral cancer in experimental hamsters
      Min Liu, Chengquan Wen, Shengqi Pan
      Veterinary Medicine and Science.2021; 7(5): 2015.     CrossRef
    • Human papillomavirus: footprints in the population of western India
      Ashi Robert Thobias, Kinjal Ankit Patel, Supreet Dhananjay Bhatt, Kruti Ashvinkumar Mehta, Chetana Deepal Parekh, Pariseema Sharad Dave, Prabhudas Shankarbhai Patel
      Epidemiology and Health.2021; 43: e2021013.     CrossRef
    • Gabapentin for cessation of smoking and non-smoking tobacco habits in Indian population
      Akhilanand CHAURASIA, Saman ISHRAT, Rini TIWARI
      Minerva Dental and Oral Science.2021;[Epub]     CrossRef
    • Outcome and treatment toxicity in east-indian versus white-canadian patients with oral cavity cancer following postoperative (chemo-)radiotherapy delivered under similar multidisciplinary care: A propensity-matched cohort study
      Shivakumar Gudi, Brian O'Sullivan, Ali Hosni, Jie Su, Andrew Hope, Jolie Ringash, Katrina Hueniken, Geoffrey Liu, Li Tong, David Goldstein, John de Almeida, Aaron R. Hansen, Scott V. Bratman, John Cho, Meredith Giuliani, Ezra Hahn, John Kim, Wei Xu, John
      Oral Oncology.2021; 120: 105419.     CrossRef
    • Safe Delivery of Surgical Care in Head and Neck Cancer Patients During COVID-19—an Audit of Pattern of Presentation and Treatment Strategies in an Oncology Centre in the Northern India
      Dipti Daga, Aseem Mishra, Sudhendu Shekhar Sharma, Atul Kumar Rai, Sunil Kumar Valsareddy, Udai Singh, Uddalak Chattopadhyay, Gautam Prakash
      Indian Journal of Surgical Oncology.2021; 12(S2): 250.     CrossRef
    • Awake tracheal intubation during COVID-19 pandemic: An audit of 23 cases in a tertiary cancer centre
      Rudranil Nandi, Kruti Bhajikhav, Nandita Gupta, AngshumanRudra Pal, Neha Desai, Jyotsna Goswami
      Airway.2021; 4(2): 79.     CrossRef
    • Epidemiological Assessment of Oral Cancer Burden in PakistanEpidemiology of oral cancer in Pakistan
      Naila Malkani, Sara Kazmi, Muhammad Usman Rashid
      Cancer Investigation.2021; : 1.     CrossRef
    • Identification & correlation of bacterial diversity in oral cancer and long-term tobacco chewers- A case-control pilot study
      Shriya Sawant, Jinesh Dugad, Deepak Parikh, Sathiyaraj Srinivasan, Harinder Singh
      Journal of Medical Microbiology .2021;[Epub]     CrossRef
    • Perceptions and Practices of General Practitioners towards Oral Cancer and Emerging Risk Factors among Indian Immigrants in Australia: A Qualitative Study
      Nidhi Saraswat, Rona Pillay, Neeta Prabhu, Bronwyn Everett, Ajesh George
      International Journal of Environmental Research and Public Health.2021; 18(21): 11111.     CrossRef
    • Global, regional, and national burden and quality of care index (QCI) of lip and oral cavity cancer: a systematic analysis of the Global Burden of Disease Study 1990–2017
      Ahmad Sofi-Mahmudi, Masoud Masinaei, Erfan Shamsoddin, Marcos Roberto Tovani-Palone, Mohammad-Hossein Heydari, Shervan Shoaee, Erfan Ghasemi, Sina Azadnajafabad, Shahin Roshani, Negar Rezaei, Mohammad-Mahdi Rashidi, Reyhaneh Kalantar Mehrjardi, Amir Ali H
      BMC Oral Health.2021;[Epub]     CrossRef
    • New Scenarios in Pharmacological Treatments of Head and Neck Squamous Cell Carcinomas
      Cristina Porcheri, Thimios A. Mitsiadis
      Cancers.2021; 13(21): 5515.     CrossRef
    • Smokeless tobacco use and reproductive outcomes among women: a systematic review
      A.G. Radhika, Sutapa B. Neogi, Preetha GS, Sumant Swain, Jaswinder Kaur, Jagdish Kaur
      F1000Research.2021; 10: 1171.     CrossRef
    • Nasopharyngeal carcinoma: A new synthesis of literature data (Review)
      Daniela Jicman (Stan), Elena Niculet, Mihaela Lungu, Cristian Onisor, Laura Rebegea, Doinita Vesa, Laura Bezman, Florin Bujoreanu, Mihaela Sarbu, Raul Mihailov, Silvia Fotea, Alin Tatu
      Experimental and Therapeutic Medicine.2021;[Epub]     CrossRef
    • Association of Demographic Details with the Onset of Precancerous Lesions in Bengaluru Population
      Shweta Sharma, Karishma Jain, Dilip N., Puneet Shetty, Chethana T.
      Kristu Jayanti Journal of Core and Applied Biology (KJCAB).2021; : 22.     CrossRef
    • Betel Nut (areca) and Smokeless Tobacco Use in Myanmar
      Roger L. Papke, Indraneel Bhattacharyya, Dorothy K. Hatsukami, Ingyin Moe, Sam Glatman
      Substance Use & Misuse.2020; 55(9): 1385.     CrossRef
    • Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration
      Alpana K. Gupta, Sonam Tulsyan, Nisha Thakur, Vishwas Sharma, Dhirendra N. Sinha, Ravi Mehrotra
      Regulatory Toxicology and Pharmacology.2020; 110: 104548.     CrossRef
    • Effects of silver and gold nanoparticles phytosynthesized with Cornus mas extract on oral dysplastic human cells
      Ioana Baldea, Adrian Florea, Diana Olteanu, Simona Clichici, Luminita David, Bianca Moldovan, Mihai Cenariu, Marcela Achim, Ramona Suharoschi, Sorina Danescu, Adriana Vulcu, Gabriela Adriana Filip
      Nanomedicine.2020; 15(1): 55.     CrossRef
    • Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer
      Gang Xue, Yao Feng, Jia-Bin Li
      World Journal of Clinical Cases.2020; 8(5): 874.     CrossRef
    • Management of early oral cavity squamous cancers
      Abhishek Chatterjee, Sarbani Ghosh Laskar, Devendra Chaukar
      Oral Oncology.2020; 104: 104627.     CrossRef
    • Cancer Prevention in Low-Resource Countries: An Overview of the Opportunity
      Sailaja Kamaraju, Jeffrey Drope, Rengaswamy Sankaranarayanan, Surendra Shastri
      American Society of Clinical Oncology Educational Book.2020; (40): 72.     CrossRef
    • Impact of COVID-19 on the early detection of oral cancer: A special emphasis on high risk populations
      Sadeq Ali AL-Maweri, Esam Halboub, Saman Warnakulasuriya
      Oral Oncology.2020; 106: 104760.     CrossRef
    • Status and strategies for the management of head and neck cancer during COVID‐19 pandemic: Indian scenario
      Anand Gupta, Vipin Arora, Deepa Nair, Nishant Agrawal, Yu‐xiong Su, F Christopher Holsinger, Jason Y K Chan
      Head & Neck.2020; 42(7): 1460.     CrossRef
    • Betel Quid, Health, and Addiction
      Roger L. Papke, Dorothy K. Hatsukami, Thaddeus A. Herzog
      Substance Use & Misuse.2020; 55(9): 1528.     CrossRef
    • Metal-induced oxidative stress: an evidence-based update of advantages and disadvantages
      Madiha Khalid, Shokoufeh Hassani, Mohammad Abdollahi
      Current Opinion in Toxicology.2020; 20-21: 55.     CrossRef
    • A qualitative study of gutka and paan masala use among Bhutanese and Burmese migrants in Georgia
      Elizabeth Thai Thanh Do, Milkie Vu, Neal Doran
      PLOS ONE.2020; 15(8): e0237266.     CrossRef
    • Interaction of human oral cancer and the expression of virulence genes of dental pathogenic bacteria
      Mansour Moghimi, Ronak Bakhtiari, Jalil Fallah Mehrabadi, Nagar Jamshidi, Nazanin Jamshidi, Abolghasem Siyadatpanah, Watcharapong Mitsuwan, Veeranoot Nissapatorn
      Microbial Pathogenesis.2020; 149: 104464.     CrossRef
    • Role of Oral Bacteria in the Development of Oral Squamous Cell Carcinoma
      Qinyang Li, Yao Hu, Xuedong Zhou, Shiyu Liu, Qi Han, Lei Cheng
      Cancers.2020; 12(10): 2797.     CrossRef
    • In Amarpur village, Uttar Pradesh, India, May 2019: A cross-sectional study
      AliJan Nazari, NaveenH Simon, Ajoke Akinola, Muskan Kaushik
      CHRISMED Journal of Health and Research.2020; 7(2): 115.     CrossRef
    • Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice
      Shannon Doherty Lyons, Jason L. Blum, Carol Hoffman-Budde, Pamela B. Tijerina, M. Isabel Fiel, Daniel J. J. Conklin, Francesca Gany, Joseph A. Odin, Judith T. Zelikoff
      International Journal of Environmental Research and Public Health.2020; 17(21): 7895.     CrossRef
    • Global impact of tobacco control policies on smokeless tobacco use: a systematic review protocol
      Monika Arora, Aastha Chugh, Neha Jain, Masuma Mishu, Melanie Boeckmann, Suranji Dahanayake, Jappe Eckhardt, Sarah Forberger, Rumana Huque, Mona Kanaan, Zohaib Khan, Ravi Mehrotra, Muhammad Aziz Rahman, Anne Readshaw, Aziz Sheikh, Kamran Siddiqi, Aishwarya
      BMJ Open.2020; 10(12): e042860.     CrossRef
    • Effect of Areca Nut on Oral Health: A Review
      M Shirzaiy, F Neshat
      Journal of Research in Dental and Maxillofacial Sciences.2020; 5(3): 1.     CrossRef
    • Patterns of Tobacco Use and its Relation to Oral Precancers and Cancers among Individuals Visiting a Tertiary Hospital in South India
      Ravikiran Ongole, Aarish Khan, Joanna Baptist, Natarajan Srikant, Fatema Lukmani
      The Journal of Contemporary Dental Practice.2020; 21(3): 304.     CrossRef
    • COVID-19 and Its Impact on Tobacco Use – Is India Prepared to Unlock the link?
      Radhakrishnan Jayakrishnan
      European Journal of Medical and Health Sciences.2020;[Epub]     CrossRef
    • Cisplatin Every 3 Weeks Versus Weekly With Definitive Concurrent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck
      Joshua M Bauml, Ravi Vinnakota, Yeun-Hee Anna Park, Susan E Bates, Tito Fojo, Charu Aggarwal, Sewanti Limaye, Nevena Damjanov, Jessica Di Stefano, Christine Ciunci, Eric M Genden, Juan P Wisnivesky, Rocco Ferrandino, Ronac Mamtani, Corey J Langer, Roger B
      JNCI: Journal of the National Cancer Institute.2019; 111(5): 490.     CrossRef
    • Differential expression of salivary S100A7 in oral submucous fibrosis
      Muhammad Arsalan Raffat, Naila Irum Hadi, Mervyn Hosein, Adnan Mustafa Zubairi, Sana Ikram, Zohaib Akram
      The Saudi Dental Journal.2019; 31(1): 39.     CrossRef
    • Grass roots approach to control levels of carcinogenic nitrosamines, NNN and NNK in smokeless tobacco products
      Alpana K. Gupta, Sonam Tulsyan, Mausumi Bharadwaj, Ravi Mehrotra
      Food and Chemical Toxicology.2019; 124: 359.     CrossRef
    • DARK Classics in Chemical Neuroscience: Arecoline
      Andrey D. Volgin, Alim Bashirzade, Tamara G. Amstislavskaya, Oleg A. Yakovlev, Konstantin A. Demin, Ying-Jui Ho, Dongmei Wang, Vadim A. Shevyrin, Dongni Yan, Zhichong Tang, Jingtao Wang, Mengyao Wang, Erik T. Alpyshov, Nazar Serikuly, Edina A. Wappler-Guz
      ACS Chemical Neuroscience.2019; 10(5): 2176.     CrossRef
    • Smokeless Tobacco and Its Adverse Effects on Hematological Parameters: A Cross-Sectional Study
      Anjani Kumar Shukla, Tanya Khaitan, Prashant Gupta, Shantala R. Naik
      Advances in Preventive Medicine.2019; 2019: 1.     CrossRef
    • GC-MS Analysis and Cytotoxicity Evaluation of Shammah (Smokeless Tobacco) Samples of Jazan Region of Saudi Arabia as Promoter of Cancer Cell Proliferation
      Asaad Khalid, Hassan A. Alhazmi, Ashraf N. Abdalla, Waquar Ahsan, Shahnaz Sultana, Mohammed Al Bratty, Sadique A. Javed, Zia ur Rehman
      Journal of Chemistry.2019; 2019: 1.     CrossRef
    • How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens—a Review Article
      Shajedul Islam, Malsantha Muthumala, Hirofumi Matsuoka, Osamu Uehara, Yasuhiro Kuramitsu, Itsuo Chiba, Yoshihiro Abiko
      Current Oncology Reports.2019;[Epub]     CrossRef
    • Oral Cavity Cancer in the Indian Subcontinent – Challenges and Opportunities
      N. Mummudi, J.P. Agarwal, S. Chatterjee, I. Mallick, S. Ghosh-Laskar
      Clinical Oncology.2019; 31(8): 520.     CrossRef
    • Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells
      Datta, Patil, Patel, Babu, Raja, Nanjappa, Mangalaparthi, Dhaka, Rajagopalan, Deolankar, Kannan, Kumar, Prasad, Mathur, Kumari, Manoharan, Coral, Murugan, Sidransky, Gupta, Gupta, Khanna-Gupta, Chatterjee, Gowda
      Cells.2019; 8(9): 949.     CrossRef
    • Association of smokeless tobacco with oral cancer: A review of systematic reviews
      Smita Asthana, Parul Vohra, Satyanarayana Labani
      Tobacco Prevention & Cessation.2019;[Epub]     CrossRef
    • Correlation of urinary cotinine with cardiovascular risk factors in pan masala tobacco users
      Sanjeeb Shrestha, Deebya Raj Mishra, Niraj Dhakal, Suresh Bhandari, Sagar Khanal, Madhab Lamsal
      Indian Heart Journal.2019; 71(6): 459.     CrossRef
    • Prevalence of Oral mucosal lesions and their association with Pattern of tobacco use among patients visiting a dental institution
      Swati Verma, Hunny Sharma
      Indian Journal of Dental Research.2019; 30(5): 652.     CrossRef
    • Smokeless tobacco products profile and pictorial warning labels in India: A review
      Fareeda Shaik, Narendra Maddu
      Population Medicine.2019;[Epub]     CrossRef
    • Patterns of Tobacco Consumption among Oral Squamous Cell Carcinoma Cases Attending a Tertiary Care Dental Hospital in Coastal Karnataka of India
      Sukanya Shetty, Shankaran V Sreelatha, Vimal K Karnaker, Chitta R Chowdhury
      World Journal of Dentistry.2019; 10(5): 350.     CrossRef
    • Oral Health Behavior and Factors Influencing the Selection of Oral Hygiene Products among the Adolescent Tobacco Consumers in Jharkhand
      Virendra K Prajapati
      The Journal of Contemporary Dental Practice.2019; 20(10): 1200.     CrossRef
    • Development of α-tocopherol surface-modified targeted delivery of 5-fluorouracil-loaded poly-D, L-lactic-co-glycolic acid nanoparticles against oral squamous cell carcinoma
      Saurabh Srivastava, Shalini Gupta, Shadab Mohammad, Irfan Ahmad
      Journal of Cancer Research and Therapeutics.2019; 15(3): 480.     CrossRef
    • A Study on Tobacco Use Among School Children
      Arun Kurupath, Pankaj Sureka
      Community Mental Health Journal.2018; 54(8): 1253.     CrossRef
    • A potential association between mutations in the iNOS cDNA 3′ stretch and oral squamous cell carcinoma - A preliminary study
      Sapna Khowal, Swatantra Kumar Jain, Saima Wajid
      Meta Gene.2018; 16: 189.     CrossRef
    • Areca Nut Chewing and the Risk of Re-hospitalization and Mortality Among Patients With Acute Coronary Syndrome in Pakistan
      Muhammad Tariq Karim, Sumera Inam, Tariq Ashraf, Nadia Shah, Syed Omair Adil, Kashif Shafique
      Journal of Preventive Medicine and Public Health.2018; 51(2): 71.     CrossRef
    • Cigarette smoke and chewing tobacco alter expression of different sets of miRNAs in oral keratinocytes
      Mohd Younis Bhat, Jayshree Advani, Pavithra Rajagopalan, Krishna Patel, Vishalakshi Nanjappa, Hitendra S. Solanki, Arun H. Patil, Firdous A. Bhat, Premendu P. Mathur, Bipin Nair, T. S. Keshava Prasad, Joseph A. Califano, David Sidransky, Harsha Gowda, Adi
      Scientific Reports.2018;[Epub]     CrossRef
    • Association ofDFNA5, SYK, andNELL1variants along with HPV infection in oral cancer among the prolonged tobacco-chewers
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    Epidemiol Health : Epidemiology and Health