Individual-level factors related to dependence

In this survey, irrespective of the criteria used to define dependence, men dominated the betel-quid dependency prevalence among Taiwanese and mainland Chinese chewers and women dominated the prevalence in Malaysia and Indonesia. One previous study that examined factors affecting beginning and quitting chewing behaviours reported that Malaysian women are more likely to start and less likely to stop the chewing habit. ^{Reference Ghani, Razak, Yang, Talib, Ikeda and Axell28} These results emphasise that women who chew betel-quid should not be overlooked. In contrast to the social constraints imposed on tobacco and alcohol consumption, betel-quid chewing is publicly accepted, including use by women. ^{Reference Strickland29} Within certain Asian communities cigarette smoking is considered a male prerogative and betel-quid chewing a female habit, and women have learned the use of this substance primarily from their mothers and grandmothers. ^{Reference Pickwell, Schimelpfening and Palinkas26}

Among Hunan men the youngest age group was most affected by betel-quid dependency. Hunan is a southern province of China where betel-quid chewing is becoming prevalent. ^{Reference Tang, Jian, Gao, Ling and Zhang30} There, betel-quid is consumed in dried husks of the areca fruit marinated with diverse flavoured ingredients. This style differs from usage patterns in other populations. Recent economic growth and heavier advertising have enhanced the popularity of betel-quid chewing in Hunan. One study showed that since the 1980s the number of those chewing has increased substantially. ^{Reference Zhang and Reichart31} Young people have adopted this substance in its mint, cinnamon and orange flavours. Because China's betel-quid manufacturers and workshops have congregated in Xiangtan City in Hunan, ^{Reference Zhang and Reichart31} easy availability, low price, attractive packaging and the lack of health risk warnings have formed the macro-environment that facilitates the development of dependency among those chewing betel-quid.

We found that countries have diverse domain-level symptoms of betel-quid dependency. In Taiwan and Hunan, spending considerable time chewing betel-quid was the central indicator endorsed by men, and blue-collar workers were the major users. Because betel-quid chewing can help focus, keep users awake, heighten alertness and increase capacity for work, ^{Reference Winstock21,Reference Chu32} workers who chronically consumed betel-quid probably sought these pharmacological effects. ^{Reference Ko, Chiang, Chang and Hsieh33} We also observed that all Nepalese chewers used tobacco-added betel-quid, and relative to the other samples clustered more with ‘tolerance’ and ‘withdrawal’ symptoms (the more biology-associated domains of dependence). Preceding studies have demonstrated that nicotine-containing betel-quid is an addictive admixture that is likely to predispose people to dependent use of these substances. ^{Reference Benegal, Rajkumar and Muralidharan24} In Malaysia, Indonesia and Sri Lanka, ‘craving’ was the most common domain endorsed by participants with any betel-quid dependency. This suggests craving as a critical component for measuring betel-quid dependent use in south-east and south Asian communities. Because craving appears in ICD-10 but not in DSM-IV criteria, the DSM-5 working group incorporated craving into the new diagnostic schema for a substance use disorder. ^{Reference O'Brien34} In a recent investigation conducted to determine whether craving fits with or improves the DSM-IV criteria set for alcohol use disorders, the inclusion of craving with the existing criteria better distinguished people with and without alcohol problems. ^{Reference Keyes, Krueger, Grant and Hasin35}

A linear trend towards increased risk of betel-quid dependency with less schooling was observed for both men and women in Taiwan, Malaysia and Sri Lanka. This presents a challenging task for health education against betel-quid use because of its pervasive culture-derived features and favourable pharmacological effects. Some ethnic groups even treat betel-quid as an innocuous substance like coffee or tea. ^{Reference Bhat, Blank, Balster and Nichter25} In one recent Sri Lankan survey, 76% of participants, primarily from lower socioeconomic groups, were unaware of any ill effects from areca nut use. ^{Reference Amarasinghe, Usgodaarachchi, Johnson, Lalloo and Warnakulasuriya36} In Indian communities, people were aware of higher cancer risks for gutka and tobacco use. However, awareness of detrimental health risks from betel-quid chewing remains limited. ^{Reference Gunaseelan, Sankaralingam, Ramesh and Datta37}

Alcohol drinking is a concomitant habit with betel-quid use in several cultures. ^{Reference Lee, Ko, Warnakulasuriya, Yin, Sunarjo and Zain1} We found that those who drank alcohol were more likely to be dependent on betel-quid in Taiwan, mainland China, Malaysia, Nepal and Sri Lanka (adjusted OR 2.1–12.7). Tobacco smoking was also found to predict betel-quid dependent use (adjusted OR 3.8–5.0) in the two Chinese populations. However, in Malaysia and Indonesia, where tobacco-added betel-quid is commonly used, smoking was associated with a lower probability of betel-quid dependency. Because tobacco-added betel-quid chewing was inversely correlated with tobacco smoking (r = –0.17 and –0.57 for Malaysia and Indonesia respectively; both P<0.001), such betel-quid consumption may competitively diminish tobacco smoking in betel-quid dependency.

Chewing quantity and frequency were found to be the most significant factors for dependency, which was also observed in one Indian study as the chewing characteristics that contributed substantially to the DSM-IV criteria for areca nut dependence. ^{Reference Benegal, Rajkumar and Muralidharan24} For our Sri Lankan sample, using tobacco-added betel-quid conferred a higher risk of dependency than using tobacco-free mixtures. Such findings have been replicated ^{Reference Benegal, Rajkumar and Muralidharan24} and suggest that the addictive ingredient of tobacco (i.e. nicotine) may increase dependence on tobacco-added products. In Hunan, a family history of betel-quid use was another predictor of dependence. A previous study indicated that the father and grandfather are the most influential family members for inducing the first chewing habit in an adolescent. ^{Reference Lu, Lan, Hsieh, Yang, Ko and Tsai38} Family-based preventive programmes may be an effective approach to reducing betel-quid dependency in Hunan.

TABLE 4

Prevalence and odds ratios of oral potentially malignant disorders associated with divergent degree of betel-quid use

				Oral lichen planus					Oral submucous fibrosis					Oral leukoplakia					OPMD
	Sample size, n			Prevalence, %			ORFootnote a		Prevalence, %			ORFootnote a		Prevalence, %			ORFootnote a		Prevalence, %			ORFootnote a
	NC	NDC	DC	NC	NDC	DC	NDC v. NC	DC v. NC	NC	NDC	DC	NDC v. NC	DC v. NC	NC	NDC	DC	NDC v. NC	DC v. NC	NC	NDC	DC	NDC v. NC	DC v. NC
Taiwan	1300	38	29	0.1	6.5	6.4	60.5Footnote *	70.4Footnote *	0.0	6.5	11.4	7.6Footnote b	46.5Footnote * Footnote b	0.03	3.8	4.5	20.0Footnote *	26.7Footnote *	0.1	10.4	11.4	39.1Footnote *	51.5Footnote *
China	1991	199	98	0.1	0.0	1.1	NA	18.3Footnote *	0.05	4.5	6.0	138.5Footnote *	186.0Footnote *	0.1	1.0	0.0	13.1	NA	0.2	4.5	7.0	30.2Footnote *	47.8Footnote *
Malaysia	682	156	140	0.0	0.0	0.0	NA	NA	0.0	0.0	0.0	NA	NA	0.0	0.0	0.0	NA	NA	0.0	0.0	0.0	NA	NA
Indonesia	995	76	748	4.3	17.3	15.5	12.8Footnote *	12.4Footnote *	3.4	3.2	9.5	1.5	5.0Footnote *	6.0	2.7	19.0	1.5	16.5Footnote *	10.4	16.6	31.2	5.6Footnote *	16.2Footnote *
Nepal	624	4	374	0.0	0.0	0.0	NA	NA	0.1	0.0	0.0	NA	NA	0.1	0.0	0.9	NA	4.7	0.3	0.0	0.9	NA	2.5
Sri Lanka	854	151	38	0.0	0.0	0.0	NA	NA	0.03	0.0	0.0	NA	NA	0.0	0.0	1.9	NA	2.0b	0.03	0.0	2.0	NA	22.6Footnote *

DC, dependent chewers (defined as meeting either DSM-IV or ICD-10 criteria); NA, non-appreciable; NC, non-chewers; NDC, non-dependent chewers; OPMD, oral potentially malignant disorders.

^a Odds ratios adjusted for gender, age, alcohol drinking and tobacco smoking.

^b Odds ratios calculated using the median unbiased estimates with the aid of exact logistic regression.

^* P<0.05.

Environmental factors and dependency

Environmental access to betel-quid is a sociological concern. A report from India showed that betel-quid availability in a person's surroundings is closely associated with its use. ^{Reference Chaturvedi39} In this study we observed five environmental promotion factors, such as aggressive marketing of betel-quid products in Nepalese communities. All Nepalese chewers were found to be users of tobacco-added products. The greater addictive properties of tobacco-added betel-quid, combined with its easy availability, may partially explain the high prevalence of betel-quid dependency (39%) observed in Nepal.

In campaigns against chewing, the Taiwan government designated 3 December as Betel Quid Prevention Day, alluding to the 123-fold increase in oral cancer risk for betel-quid chewers who concurrently consumed alcohol and cigarettes. ^{Reference Ko, Huang, Lee, Chen, Lin and Tsai12} The outcome of the campaigns was a 21% reduction in betel-quid production in 2010 (130 000 tonnes) relative to the year 2000 peak (165 000 tonnes). ⁴⁰ These actions explain the lower prevalence of betel-quid dependency found in Taiwan. However, in places where such health promotions do not yet exist, such as Hunan, betel-quid is widely marketed on television as a safe mouth freshener. In recent years, betel-quid has become one of the most important local industries, with an annual gross economic value approaching US$1.18 billion. If current trends continue unabated, the availability of betel-quid will create a new generation of chewers among young people. ^{Reference Lee, Ko, Warnakulasuriya, Yin, Sunarjo and Zain1}

Betel-quid dependency and OPMD

Most authorities agree that OPMD prevalence ranges from 1% to 5%, according to geographic region, population characteristics and patterns of substance use. ^{Reference Napier and Speight41} The annual proportion of OPMD that develops into oral squamous cell carcinoma remains undetermined, but the current best estimates are <0.1% for oral lichen planus, 0.5% for oral submucous fibrosis and 1% for oral leukoplakia. ^{Reference Van der Waal42} Evidence from previous studies shows that oral submucous fibrosis is a disorder not limited to the oral cavity; it may extend beyond the mouth to the oesophagus (66% of patients with oral submucous fibrosis show histological abnormalities in the oesophagus). ^{Reference Misra, Misra, Dwivedi and Gupta43} Consistent with the IARC report, ⁶ we observed that people who chewed betel-quid had high prevalence rates of OPMD, especially if they were dependent users. In area-combined data, dependency levels and OPMD risk demonstrated dose–effect findings, regardless of the criteria used. Despite progress in molecular biology, no single biomarker has been identified to predict OPMD malignant transformations. ^{Reference Van der Waal42} Our results showed that the risk of OPMD in participants with non-dependent betel-quid use (0–2 dependency domains) was 4.5–5.9 times greater than in the non-chewers group, increasing to 8.0–51.3 among those with dependency. These findings disclose the significance of considering people with betel-quid dependency as an important screening target in the prevention and control of OPMD, and stress that those whose betel-quid use is non-dependent should not be neglected in oral examination programmes.

TABLE 5

Prevalence and adjusted odds ratios of oral potentially malignant disorders associated with the number satisfying DSM-IV and ICD-10 domains for betel-quid dependence: combined results from six Asian populations

	Sample size, n	Prevalence of OPMD, %	ORFootnote a (95% CI)
Non-chewers	6451	4.3	1.0 (reference)
Current chewers
No. of DSM-IV domains
0-2 (non-dependence)	704	7.3	5.9 (2.8-12.7)
3-4	1040	16.9	8.0 (4.5-14.3)
5-6	280	42.4	27.5 (10.8-69.6)
7	36	47.8	51.3 (16.5-159.9)
P for linear trend		<0.001	<0.001
No. of ICD-10 domains
0-2 (non-dependence)	872	7.3	4.5 (2.4-8.6)
3-4	966	31.3	20.5 (8.7-48.2)
5-6	222	33.9	23.0 (11.0-48.2)
P for linear trend		<0.001	<0.001

OPMD, oral potentially malignant disorders (including oral lichen planus, oral submucous fibrosis and oral leukoplakia).

^a Adjusted for gender, age, alcohol drinking, tobacco smoking and study population.

Strengths and limitations

Because betel-quid chewing was publicly accepted in all groups in the study, participants were comfortable revealing their usage; therefore, this may have diminished underreporting of the extent of betel-quid dependent use. Because of the cross-sectional nature of the results, our study presents only a snapshot of betel-quid dependency for the study populations. Furthermore, chewing practices and ingredients diverge by area. The findings in this survey should not be generalised to other areas within the respective countries. However, the research methodology and network might be extended to countries where betel-quid usage is common, such as Cambodia, Laos and Vietnam.

Implications

This study draws immediate attention to the population-level psychiatric problems of betel-quid chewing in six Asian communities where it is widely consumed. The findings disclose the role of sociodemographic factors, other substance use and environmental approachability in betel-quid dependency, and its health impact on OPMD. An understanding of these factors can facilitate implementation of health promotion measures and the adequate management of the OPMD burden resulting from betel-quid chewing.