Defining a global research and policy agenda for betel quid and areca nut

Abstract

Betel quid and areca nut are known risk factors for many oral and oesophageal cancers, and their use is highly prevalent in the Asia-Pacific region. Additionally, betel quid and areca nut are associated with health effects on the cardiovascular, nervous, gastrointestinal, metabolic, respiratory, and reproductive systems. Unlike tobacco, for which the WHO Framework Convention on Tobacco Control provides evidence-based policies for reducing tobacco use, no global policy exists for the control of betel quid and areca nut use. Multidisciplinary research is needed to address this neglected global public health emergency and to mobilise efforts to control betel quid and areca nut use. In addition, future research is needed to advance our understanding of the basic biology, mechanisms, and epidemiology of betel quid and areca nut use, to advance possible prevention and cessation programmes for betel quid and areca nut users, and to design evidence-based screening and early diagnosis programmes to address the growing burden of cancers that are associated with use.

Full text

www.thelancet.com/oncology Vol 18 December 2017
e767
Policy Review
Defining a global research and policy agenda for betel quid
and areca nut
Hedieh Mehrtash*, Kalina Duncan*, Mark Parascandola*, Annette David, Ellen R Gritz, Prakash C Gupta, Ravi Mehrotra,
Amer Siddiq Amer Nordin, Paul C Pearlman, Saman Warnakulasuriya, Chi-Pang Wen, Rosnah Binti Zain, Edward L Trimble
Betel quid and areca nut are known risk factors for many oral and oesophageal cancers, and their use is highly
prevalent in the Asia-Pacific region. Additionally, betel quid and areca nut are associated with health eects on the
cardiovascular, nervous, gastrointestinal, metabolic, respiratory, and reproductive systems. Unlike tobacco, for which
the WHO Framework Convention on Tobacco Control provides evidence-based policies for reducing tobacco use, no
global policy exists for the control of betel quid and areca nut use. Multidisciplinary research is needed to address this
neglected global public health emergency and to mobilise eorts to control betel quid and areca nut use. In addition,
future research is needed to advance our understanding of the basic biology, mechanisms, and epidemiology of betel
quid and areca nut use, to advance possible prevention and cessation programmes for betel quid and areca nut users,
and to design evidence-based screening and early diagnosis programmes to address the growing burden of cancers
that are associated with use.
Introduction
Hundreds of millions of people worldwide are estimated
to consume betel quid or areca nut (the primary
ingredient in betel quid), or both, in some form.1
Consumption is especially prevalent in the Asia-Pacific
region, including in India, Bangladesh, Myanmar, Sri
Lanka, Taiwan, Papua New Guinea, Cambodia, and
Malaysia, and worldwide among emigrants of those
countries. Both betel quid and areca nut have been
classified as carcinogenic to human beings (Group 1) by
the International Agency for Cancer Research (IARC),2
and areca nut has been shown to be associated with
dependence in users.3,4 However, betel quid and areca nut
use has not received much attention from public health
researchers and policy makers. A large global movement
now exists to advance tobacco control through the WHO
Framework Convention on Tobacco Control and other
regulations, but so far these eorts have focused
primarily on smoking, with not as much progress seen
for smokeless tobacco use.5 Although tobacco-control
policies can apply to betel quid and areca nut products
containing tobacco, many people use these without
consuming tobacco as well. Moreover, the use of betel
quid and areca nut poses an especially complex and
widespread public health challenge because of the
scarcity of data on the wide variety of products and
practices associated with their use, and the emphasis on
local cottage-industry production, which can be dicult
to regulate. Other complicating factors include multiple
substance use (eg, the simultaneous use of tobacco, betel
quid, areca nut, and alcohol), use among individuals who
do not traditionally use tobacco or other substances, the
perception that betel quid and areca nut products are
socially and culturally important, the addictive nature of
betel quid and areca nut products, and the high oral
cancer incidence and mortality in the aected countries.
An international group of scientific and public health
leaders met in April, 2016, in Kuala Lumpur, Malaysia, to
identify research needs and discuss opportunities to
reduce the prevalence of betel quid and areca nut use and
the incidence of oral cancers related to their use. The
International Conference on Betel Quid and Areca Nut
was organised by the University of Malaya (Kuala
Lumpur, Malaysia), the US National Cancer Institute and
National Institute for Dental and Craniofacial Research
(Bethesda, MD, USA), the Taiwan Health Promotion
Administration (Taipei, Taiwan), and the MD Anderson
Cancer Center (Houston, TX, USA). The conference
addressed six key themes: the biology of betel quid and
areca nut related diseases, the epidemiology of betel quid
and areca nut use, factors that influence betel quid and
areca nut use and addiction, interventions for prevention
and cessation, screening and early diagnosis of betel
quid and areca nut related cancers, and policies for
control. In this Policy Review, we present the findings
from this meeting. Recommendations have been
supported by 130 meeting participants from 21 countries.
We also aim to provide a call to action to reduce betel
quid and areca nut use and its associated global oral
cancer burden, by acting on the existing evidence and
addressing important research gaps.
Products, patterns of use, and cancer effects
Areca nut is among the most widely used psychoactive
substances worldwide along with tobacco, alcohol, and
caeine. The Asian Betel Quid Consortium (ABC) study
(undertaken in 2009–10 in Taiwan, mainland China,
Malaysia, Indonesia, Nepal, and Sri Lanka) found that
the prevalence of betel quid and areca nut chewing in the
adult population varied from 10·3% in Malaysia to 43·6%
in Nepal for men, and from 2·3% in mainland China to
47·8% in Indonesia among women.6 In Malaysia and
Indonesia, use was higher for women (32·1% and 47·8%,
respectively) than for men (10·3% and 12·4%,
respectively). However, unlike for tobacco use, no
systematic global or regional surveillance exists for betel
quid and areca nut use in their various forms. A previous
report7 estimated that 600 million people use betel quid
Lancet Oncol 2017; 18: e767–75
*Contributed equally
National Cancer Institute,
National Institutes of Health,
Rockville, MA, USA
(H Mehrtash MPH,
K Duncan MPH,
M Parascandola PhD,
P C Pearlman PhD,
E L Trimble MD); Health
Partners LLC, Tamuing, GU,
USA (A David MD); MD
Anderson Cancer Center,
University of Texas, Houston,
TX, USA (E R Gritz PhD); Healis
Sekhsaria Institute for Public
Health, Mumbai, India
(P C Gupta ScD); National
Institute of Cancer Prevention
and Research and WHO-FCTC
Smokeless Tobacco Global
Knowledge Hub, Uttar Pradesh,
India (R Mehrotra, MD);
Department of Oral Medicine,
King’s College London and
WHO Collaborating Centre for
Oral Cancer and Precancer,
London, UK
(S Warnakulasuriya PhD);
National Health Research
Institutes, Zhunan, Taiwan
(C-P Wen MD); Graduate
Institute of Biomedical
Sciences, College of Medicine
and Department of Medical
Research, China Medical
Univerity, Taichung, Taiwan
(C-P Wen); and Faculty of
Medicine
(A S Amer Nordin MPM) and
Oral Cancer Research and
Coordinating Centre, Faculty of
Dentistry (R B Zain MS),
University of Malaya, Kuala
Lumpur, Malaysia
Correspondence to:
Ms Hedieh Mehrtash, National
Cancer Institute, National
Institutes of Health, Rockville,
MD 20850, USA
hedieh.mehrtash@nih.gov

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and areca nut, but given the paucity of data available such
estimates have a substantial degree of uncertainty.7
Betel quid and areca nut are used to prepare a wide
variety of products (table). Betel quid and areca nut
products are typically a mixture of areca nut and slaked
lime wrapped in a betel leaf with added flavourings. The
areca nut is the seed of the areca palm, and the betel leaf
comes from the Piper betle vine; areca nut is sometimes
incorrectly referred to as betel nut.2 The addition of
slaked lime increases the pH of the product and results
in increased delivery and absorption of psychoactive
ingredients such as arecoline and, in products containing
tobacco, nicotine. A wide variety of flavouring ingredients
can be used that vary by geographical region and local
tastes, including traditional spices (eg, cardamom,
saron, cloves, anise, turmeric, and mustard), sweeteners
(eg, coconut and dried dates), and other flavourings (eg,
menthol and mint).11 Areca nut is used in other
preparations as well—eg, in some areas of mainland
China the husk of the areca nut is chewed without
tobacco or other flavourings, and in India areca nut
appears in mouth fresheners and other products.2 The
use of areca nut wrapped in betel leaf is common in the
Federated States of Micronesia and Cambodia, whereas
the use of areca nut without the betel leaf is more
common in other Pacific islands,8 and the whole unripe
areca fruit is consumed by Pacific Islanders and in
Taiwan. Betel quid and areca nut products (eg, pan
masala) are often locally produced without
standardisation. Toxic industrial dyes used as colourants
have been found in imported betel quid and areca nut
products (Mozek A, New York State Agriculture, personal
communication). Little information is available about the
characteristics of dierent product formulations.5,12
Both betel quid and areca nut have been classified as
carcinogenic to human beings (Group 1) by the IARC,
both when used with or without tobacco.2 In particular,
the 2004 IARC monograph concluded that evidence is
sucient to show that betel quid and areca nut products
without tobacco cause oral cancer, whereas betel quid
and areca nut products with tobacco cause oral cancer
and cancer of the pharynx and oesophagus.2 Oral cancer
is the 11th most common cancer in the world, with an
estimated 300 000 new cases and 145 000 deaths in
2012.13 Incidences of oral cancer vary geographically and
are especially high in countries in the Asia-Pacific region
where betel quid and areca nut use is most common.7,13,14
Estimates also suggest that betel quid and areca nut use
could account for up to 50% of oral cancers in some
countries, of which two-thirds are in low-income and
middle-income countries.13–15 In addition, India alone
accounts for a fifth of all oral cancer cases and a quarter
of all oral cancer deaths worldwide.13 In a large cohort
study16 in India, all oral cancers developed from
potentially malignant oral disorders or precancerous
lesions and were seen among users of betel quid, areca
nut, or tobacco-based products, or all of these. Potentially
malignant oral disorders related to betel quid and areca
nut product use include oral submucous fibrosis, oral
leukoplakia and erythroplakia, and oral lichenoid
lesions.13 The relative risk of developing oral cancer
among individuals with such lesions compared with
Countries of use5,8 Product definitions (form and type of tobacco and added ingredients)
Areca nut husk without
tobacco9
Mainland China Custom-made or handmade product that consists of the husk of the Piper betle plant mixed with other
ingredients (eg, dried grapes)
Betel quid with tobacco
(eg, paan)5,10
Bangladesh, Cambodia, China, Indonesia, India, Federated
States of Micronesia, Laos, Malaysia, Maldives, Myanmar,
Papau New Guinea, Nepal, Pakistan, Palau, Singapore, Sri
Lanka, Taiwan, Thailand, United Arab Emirates, UK, Vietnam
Commercial or vendor-prepared packaged product, or handmade or home prepared by the user with
tobacco; contains areca nut, slaked lime, betel leaf, and often catechu; other ingredients are added that
differ regionally such as cardamom, saffron, cloves, aniseed, turmeric, mustard, sweeteners, rosewater,
aniseed, mint, or other spices
Betel quid (without
tobacco)5,3
Taiwan, Papau New Guinea, Solomon Islands Custom-made or handmade product that is a combination of betel leaf, areca nut, or fruit of a pepper
plant (Piper betle), and powdered lime; other ingredients and spices can be added to enhance
flavouring; often prepared by wrapping the areca nut, and part of the betel pepper vine with or without
the other ingredients in a Piper betle leaf
Gutkha or gutka5,10 Bangladesh, India, Myanmar, Nepal, Pakistan, Sri Lanka Commercially manufactured and packaged form of tobacco product containing crushed areca nut and
catechu that are mixed together with various flavourings and sometimes sweeteners
Khaini, khoini5,10 Bangladesh, Bhutan, India, Nepal Commercially prepared or custom-made product containing powdered tobacco mixed with slaked lime
paste and sometimes areca nut
Mainpuri5Uttar Pradesh, India Handmade or custom-made product containing tobacco, areca nut, camphor, and cloves
Mawa, kharra5Gujarat, Maharashtra, India Handmade or custom-made product or locally produced and wrapped in cellophane, containing small
pieces of areca nut (95%) that are mixed with tobacco flakes and slaked lime, then the mixture is
rubbed together to combine
Naswar (niswar)5,10 Afghanistan, India, Pakistan Custom-made form of tobacco that is a combination of ingredients including slaked lime, ash, oil,
sometimes flavourings (most commonly menthol and cardamom), and a colouring agent (such as indigo)
Zaarda or zarda5,10 Bangladesh, Bhutan, India, Myanmar, Nepal, UK, Yemen Commercially produced product containing tobacco, lime, spices, vegetable dyes, and sometimes areca
nut; processed with broken tobacco leaves boiled with lime and spices; the mixture is dried and
coloured with vegetable dyes, then sometimes mixed with areca nut
Table: A selection of key betel quid and areca nut products, their common forms, and countries of use

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tobacco users without such lesions is extremely high
(ranging from 15·8 for oral lichen planus to 3243·1 for
nodular leukoplakia).17 In addition to several types of
cancer, a systematic review18 found that areca nut use
aects almost all organs of the human body and causes
or worsens conditions such as myocardial infarction,
cardiac arrhythmias, hepatotoxicity, asthma, obesity, type
2 diabetes, metabolic syndrome, hypothyroidism,
infertility, and adverse reproductive outcomes.18 Similar
to many carcinogens, a dose-dependent association has
been shown for betel quid and areca nut use and
potentially malignant oral disorders (or precancerous
lesions), including oral, pharyngeal, and oesophageal
cancers.19,20
For smokeless tobacco use, a well-documented
conceptual model21 exists to explain the carcinogenesis
process, including ingestion of carcinogens such as
N-nitrosonornicotine and nicotine-derived nitro samine
ketone, subsequent metabolic activation of carcinogens
and formation of DNA adducts, and mutations that could
ultimately lead to cancer. A similar model has not been
developed for betel quid and areca nut use, but there is a
substantial and growing literature base exploring the
related mechanisms of pathogenesis, particularly around
the biological eects of arecoline.22–25
The characteristics of a product can aect its toxicity to
users. For example, some data26 suggest mass-produced
products (eg, paan, gutka, and mawa), which tend to have
higher concentrations of areca nut than self-prepared
betel quid, are associated with a more rapid development
of oral submucous fibrosis—a potentially malignant oral
disorder. Betel quid and areca nut products that include
tobacco have elevated concentrations of nicotine and
tobacco-specific nitrosamines,27 and the products
containing tobacco are also associated with higher cancer
risks than those without tobacco.28 Other product
characteristics, such as the degree of nut ripeness,
method of processing, and presence of additional
ingredients, could also aect the product’s chemical
composition and the resulting toxicity and carcinogenicity.2
To fully characterise the public health burden of betel
quid and areca nut use and its related cancers, a range of
research questions should be addressed. Detailed
cataloguing of the diverse betel quid and areca nut
products in use and their associated ingredients is
needed to better understand product characteristics.
Systematic surveillance of betel quid and areca nut use,
the associated cancers, and other health eects is needed
as a minimum, and on a scale similar to what exists for
tobacco use. For example, betel quid and areca nut use
should be added to existing global surveillance systems,
including the Global Tobacco Control Surveillance
System, the WHO STEPwise approach to surveillance,
and Demographic Health Surveys Program. Qualitative
research studies are needed to better characterise use
patterns by gender and by dierent ethnic, cultural, and
social characteristics across countries in the Asia-Pacific
region, as well as among migrant groups in the USA and
Europe. Moreover, continued epidemiological studies are
necessary to further characterise the carcinogenic and
other potential health eects of areca nut, especially for
the use of products without tobacco to expand on the
2004 IARC monograph evaluation.
Dependence, prevention, and cessation
Areca nut, like tobacco, is addictive. Research3,29,30
suggests that a substantial proportion of betel quid and
areca nut users show signs of dependence, although
dependence is greater among those who use betel quid
and areca nut products with tobacco than among those
who use it without.3,29–31 Frequency of use has also been
reported to be higher for those people who used betel
quid and areca nut products with tobacco.32 The use of
slaked lime as an added ingredient is also associated with
higher dependency in users. A study33 across six Asian
communities (in Taiwan, mainland China, Indonesia,
Malaysia, Sri Lanka, and Nepal) found that non-tobacco
betel quid and areca nut users who added slaked lime
were much more likely to meet the criteria for
dependence from the Diagnostic and Statistical Manual
of Mental Disorders (fourth edition) than those who did
not add slaked lime (23·3–95·6% vs 4·0%, p≤0·001). A
betel quid and areca nut dependency syndrome among
Indian residents in London was first described by
Winstock and collegues,34 and a betel quid dependency
scale has been developed, similar to that used for
cigarette smoking, to assess the degree of dependence in
users of betel quid.29
However, the biological basis of betel quid and areca
nut dependence is not well understood. A range of CNS
and autonomic-nervous-system eects have been
documented in betel quid and areca nut users, including
increased heart rate, blood pressure, sweating, and body
temperature.35 Additionally, users report psychological
reactions from such products, such as a sense of
wellbeing, euphoria, a warm sensation over the body,
heightened alertness, and an increased capacity to work.
The predominant psychoactive agent in areca nut is
arecoline, an alkaloid that operates as an agonist at
muscarinic receptors, which probably accounts for the
observed CNS eects. However, research also suggests
that arecoline has an eect on select nicotinic
acetylcholine receptors, which might explain its
dependence-producing eects.36
Few studies have assessed the determinants and factors
that lead to betel quid and areca nut use. The ABC study6
found that lower education and tobacco or alcohol
consumption were associated with betel quid and areca
nut use. In some areas use begins at a very young age—
eg, one study37 in the Pacific island of Saipan found that
39% of children in ninth grade (mean age 14·7 [SD 1·0]
years) used betel quid and areca nut products.
Additionally, the likelihood of betel quid and areca nut
use could be increased by family and cultural traditions.

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Some betel quid and areca nut users describe chewing as
a positive behavioural trait associated with cultural
identity.38 Gutka users in India reported that they use
betel quid and areca nut products because they relieve
tension, aid concentration, combat bad breath, and
increase energy.39 Male betel quid and areca nut chewers
from Myanmar associated the practice with masculinity
and believed that chewing was important to social and
business interactions.40 A study41 of Bhutan health-care
providers found that individuals from families in which
more than 50% of family members used betel quid and
areca nut products were 14 times more likely to chew the
products than those from families with no chewers. In
many populations, betel quid and areca nut products are
also associated with social, cultural, and religious
rituals.42
Although evidence-based treatments exist for tobacco
dependence, evidence and proven strategies to promote
cessation in users of betel quid and areca nut products
are scare. Where data exist, quitting rates among betel
quid and areca nut users appear to be relatively low. In
Taiwan, for example, a quitting rate of only 8% was
reported among Taiwanese aborigines chewing betel
quid and areca nut products between June, 2003, and
May, 2004.43 Evidence43,44 also suggests that betel quid and
areca nut users who also smoke cigarettes or drink
alcohol regularly are less likely to successfully quit betel
quid and areca nut consumption. However, after
cessation the likelihood of developing oral lesions is
reduced.45 Moss and colleagues46 did a feasibility study of
a clinic-based cessation programme targeted at betel
quid and areca nut product users in Guam. They noted
that language, transportation, clinic accessibility, cultural
context, and the inclusion of family members were
important factors in developing a successful cessation
programme.46 Findings that arecoline acts on identical
receptors in the brain as nicotine does also raises the
possibility that treatments used for nicotine dependence
could also be eective against betel quid and areca nut
addiction.36 In line with those findings, WHO
recommends that the treatment of tobacco dependence
within health-care systems should also include
information on the dangers of areca nut use when
appropriate and oer similar behavioural and
pharmacotherapy treatments for betel quid and areca nut
cessation.8 Given the prevalence of betel quid and areca
nut use in rural and remote areas where clinic services
might be scarce but mobile phone use is high, mobile
SMS-based text-messaging interventions (mHealth)
could oer a promising method for delivering cessation
support, similar to programmes that have been developed
for tobacco cessation.47,48
Given the shortage of proven interventions tailored to
combat betel quid and areca nut use, the development
and testing of such interventions should be high-priority
research. Although interventions exist for smokeless
tobacco use, most of this work comes from high-income
countries and might not be directly applicable to regions
where betel quid and areca nut use is high.5 Although a
small number of instruments have been proposed in the
literature to assess betel quid and areca nut addiction,
they need further testing and evaluation across diverse
groups of users.49,50 A proposed scale of reasons for betel
quid and areca nut product chewing also shows promise
as a tool for future studies.50 Greater understanding of
the biological basis of areca nut dependence could aid in
the development of eective interventions. In addition to
treatment, the development and evaluation of prevention
programmes targeted at betel quid and areca nut use
among people aged 3–25 years are needed. A greater
understanding of the cultural and social conventions that
motivate the regular use of betel quid and areca nut is
also essential to inform the design of eective prevention
and intervention campaigns.42
Screening and early diagnosis of oral cancers
Screening and early diagnosis play important roles in the
management of oral cancers. Oral cancers are generally
preceded by potentially malignant disorders that can be
readily detected using conventional oral visual
examination.51 Oral visual examination is an established
method of oral cancer screening to detect the presence of
potentially malignant disorders done by trained health
professionals via a systematic visual inspection of the
oral cavity under a bright light.52,53 Early detection and
treatment of precancerous lesions can substantially
reduce cancer-specific morbidity and mortality.51,53
Alternatives to conventional oral visual examinations
include a number of established non-invasive adjunctive
screening aids, such as brush cytology, vital staining
using toluidine blue, and light-based systems.54,55
Additionally, experimental screening aids and diagnostic
tests are being developed to improve the outcome of early
diagnosis and for risk assessment and screening,
including DNA content, salivary proteomics, and
biomarkers.54–57 Evidence to support or reject these
adjunctive tools for use in screening is still insucient,
and further studies are needed to investigate their role in
oral cancer screening in primary care or community
settings.54,55 Further research is needed to select the
appropriate screening model for low-income and middle-
income countries, and evidence from a systematic
review53 and a randomised control study58 in India
suggest that screening high-risk individuals might be the
most appropriate approach.
Cost utility and cost-eectiveness are important
considerations in visual screening. Visual screening of
the oral cavity has been widely studied for its feasibility,
safety, acceptability, and accuracy to detect precancerous
lesions and cancer, and ecacy and cost-eectiveness in
reducing oral cancer mortality.52 However, for other non-
adjunctive and experimental screening aids, the
assessment of their feasibility, clinical utility, cost-
eectiveness, and eectiveness in reducing oral cancer

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Policy Review
mortality requires large-scale population-based studies.59
A study60 published in 2016 compared the health state
utility values associated with potentially malignant oral
disorders and oral cancer in Sri Lanka using a generic
quality-of-life instrument. Future studies should assess
the performance and cost-eectiveness of adjunctive
tests in cross-sectional and longitudinal studies.
Given the strong evidence of increased risk of oral (and
other) cancer with betel quid and areca nut use, users of
these products comprise a high-risk target population
who might benefit from early screening.58 For high-risk
groups, education and counselling to discourage the use
of betel quid, areca nut, and tobacco products, as well as
alcohol, are key prevention strategies.58
Health-care professionals play an important role in
contributing to prevention by assessing betel quid and
areca nut use particularly among high-risk individuals,
communicating established health risks, advising and
assisting them to stop, and documenting their usage and
outcomes.61 An Indian study45 with 5-year and 10-year
follow-ups has shown that educational interventions
reduce betel quid and areca nut chewing and decrease
the incidences of potentially malignant disorders. A
series of studies in India61 and Sri Lanka62–64 emphasised
the feasibility of utilising primary health-care workers for
the early detection of oral cancer and precancerous
lesions. In one of these studies,63 the ability to detect
these lesions was shown by the 58% positive predictive
value for a referable lesion.
Malaysia and Taiwan have taken steps to implement
national-screening programmes. The lessons that have
been learned from these programmes should be applied
to other settings where few programmes exist.
Additionally, Sri Lanka has had several ad-hoc screening
programmes over several decades and the experience
and skills gained from these activities can be built on to
help create a national screening programme.64 Malaysian
researchers65 have launched an oral cancer awareness
campaign delivered through mass media to increase
awareness about oral cancer and the importance of
screening. Although researchers found that the campaign
increased awareness around oral cancer, the proportion
of respondents who could identify the signs or symptoms
of oral cancer was still small.
The Taiwan Health Promotion Administration has
implemented a multicentre-screening programme for
oral cancer that oers free biennial oral cancer screening
to individuals in high-risk groups (older than 30 years
who are smokers or have an areca nut chewing habit).
The trial screening programmes were initiated in 1985,
and outreach services were scaled up nationally in 1999.
Data collected from these screening programmes are
integrated into a national-level screening database that
can be used for cancer surveillance.66
Given the general shortage of national oral cancer
screening programmes in low-income and middle-
income countries, two major research recommendations
have been proposed to initiate screening and early
diagnosis programmes for oral cancers. First, health-
care workforces in low-income and middle-income
countries should be assessed to determine which health-
care professions and facilities are best suited to
managing community-based and national-screening
programmes. Better training and calibrated programmes
are needed for the oral health community to
systematically check users’ oral cavities for cancer and
precancerous lesions when feasible.67 Second, formal
assessments of existing national-screening programmes
in Taiwan and Malaysia are needed, to provide
information on the successes and challenges of their
implementation. The assessment of the performance
and eectiveness of the national-screening programme
should assess factors related to the performance of
providers (eg, coverage and accuracy) and the benefits of
screening. The dierences in chewing and smoking
behaviours between people being screened and those
not being screened, and the dierent status of findings
among those being screened, should be compared.
Other factors to be considered for assessment include
improving participation, improving detection requiring
referral, increasing attendance (compliance) from
referrals, and obtaining regular reports on the sensitivity
and specificity achieved by dierent categories of health
workers. In countries that have traditionally reported
high incidences of oral cancer, screening should be
prioritised as an important preventive measure in the
delivery of public health.
Policy and economics
Unlike tobacco control, which is guided by the WHO
Framework Convention on Tobacco Control and WHO
MPOWER measures, no global policy treaty or
framework exists to provide an evidence-based platform
for reducing the burden of betel quid and areca nut use.
The WHO MPOWER measures are intended to assist
countries in implementing eective policies and
interventions to reduce the demand for tobacco
products. These measures include: (M) monitoring
tobacco use and prevention policies; (P) protecting
people from tobacco-smoke exposure; (O) oering help
to quit tobacco use; (W) warnings about the dangers of
tobacco; (E) enforcing bans on tobacco advertising,
promotion, and sponsorship; and (R) raising taxes on
tobacco. Strategies to adapt and apply eective MPOWER
measures to betel quid and areca nut use should be
explored to reduce demand and the use of betel quid and
areca nut products.68
A few countries do provide examples of novel policies to
address betel quid and areca nut use; however, the
evaluation of the success of such policies remains scarce.
Following a 2004 Indian Supreme Court ruling that
classified gutka as a food product,69 most Indian states
have banned the sale of gutka under rules that prohibit
adding any harmful ingredients, including tobacco, to a

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food product. Although some states and territories have
been relatively successful in enforcing the ban on gutka,
reports suggest that manufacturers are circumventing
these bans by selling two primary gutka ingredients—pan
masala and tobacco—in separate pouches.70–72 Additionally,
some gutka users might switch to other tobacco products
that remain on the market. Countries such as Papua New
Guinea and Myanmar have either proposed or imposed
bans on chewing betel quid and areca nut products in
public spaces. These measures have been met with
substantial resistance and whether they can be successfully
implemented remains to be seen.73 The United Arab
Emirates has imposed a ban on the importation of betel
leaf and some betel-leaf related products.74 Singapore has
also banned gutka as part of a larger eort to control so-
called emerging tobacco products.75
In the control of tobacco, research76 has shown that
taxation is one of the most consistently eective
interventions to reduce consumption at a population
level, especially among those aged 13–25 years. However,
implementation of taxes on betel quid and areca nut
products remains weak in many countries, and evidence
on the potential impact of tax and price increases on
betel quid and areca nut initiation and use is scarce. One
small study77 in India suggested that a 10% increase in
the price of gutka would decrease consumption by 5·8%
and prevalence by 2·7% in the country. Other research78
suggests that combining taxation policies for cigarettes
and betel quid and areca nut products could have
beneficial eects on cessation because the two behaviours
are closely related. An assessment of the impact of tax
parity across smoked tobacco and betel quid and areca
nut products is needed.
Areca nut is a common agricultural product. The world
production of areca nut is increasing with production
quantity varying between countries.79 India produces the
largest amount of areca nut, followed by Indonesia,
Myanmar, Bangladesh, Sri Lanka, Taiwan, and Thailand.79
Production of betel quid and areca nut is encouraged in
some countries as a commodity for both local
consumption and for export, and has become a great
source of income for some Pacific-island countries.8
Because some countries depend, to some extent, on their
income from the export and sales of areca nut, crop
substitution should be considered in any policy approach
to reduce areca nut uptake and use. Similar to work being
done in tobacco-control research,80 exploratory research
should be undertaken to identify viable alternatives for
areca nut-crop substitution, and to maintain relations
between areca nut farmers and industry.
Betel quid and areca nut products are often homemade
or manufactured within a network of small locally owned
or cottage-scale businesses. The scarcity of product
standardisation and mass commercialisation, and the
high diversity in products make policies and regulations
especially dicult to implement and enforce in dierent
settings.5 Implementation and translational research is
needed to understand how best to apply policy inter-
ventions that have been proven to be eective for the
control of tobacco. The global experience in tobacco
control, utilising the WHO Framework Convention on
Tobacco Control and MPOWER, provides a template for
future action, but more evidence is needed on how these
policies might aect betel quid and areca nut use.
Furthermore, more comprehensive information on the
betel quid and areca nut product industry, the retail
environment, and existing tax and trade policies is
needed. This research should include an assessment of
the ecacy of existing betel quid and areca nut product
bans on their use, manufacture, sales, and agriculture,
existing tax and trade policies, and implementation
challenges to identify strategies for strengthening future
legislation and improving the enforcement of policies.
In addition to evidence-based public health policies
that can impact the prevalence of betel quid and areca
nut use, translational research is needed to convert data
into eective advocacy messages. To facilitate this eort,
countries with high betel quid and areca nut prevalence
should begin multisectorial consultations to mobilise
support for betel quid and areca nut policy interventions
and research. Additionally, aected regions should
consider biregional or triregional policy consultations to
delineate a policy-action agenda and to establish a
biregional or triregional network for policy advocacy and
research. WHO and member states, especially those in
the Asia-Pacific region, should include betel quid and
Panel: Recommendations for future research directions on
betel quid and areca nut use
• Characterisation of the types of betel quid and areca nut
products and their use across populations in the
Asia-Pacific region
• Strengthen the understanding of the biological and
behavioural basis of areca nut dependence to aid in the
development of effective prevention and cessation
interventions
• Development and evaluation of targeted betel quid and
areca nut use prevention and cessation methods that
include the evaluation of existing prevention campaigns
and messages, and defining the role of health-care
providers in prevention and cessation interventions
• Study of the cultural and social conventions that motivate
the use of betel quid and areca nut products
• Quantification of the dose-response relationships between
various betel quid and areca nut products, with and without
tobacco, and the risk of oral and oesophageal cancers
• Development, evaluation, and implementation of effective
screening and early diagnosis programmes for oral cancers
• Completion and implementation of translational
research to best apply effective policy interventions in
tobacco control to this diverse field to mitigate the
potential risk of disease

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Policy Review
areca nut use in high-level health agendas and ministerial
health meetings. This suggestion follows on from a
similar call by the WHO regional committee for
southeast Asia for the integration of oral health in the
context of non-communicable diseases into their health
agenda as part of the regional action plan for 2013–20.81
Conclusion
Evidence shows that betel quid and areca nut and their
products are widely used, particularly in the Asia-Pacific
region. Use of betel quid and areca nut products induces
oral precancerous lesions that have a high tendency to
progress to oral cancers. Betel quid and areca nut products,
both with and without tobacco, have been classified as
group 1 carcinogens (carcinogenic to human beings) by
IARC. To reduce the use of betel quid and areca nut
products, and the associated burden of oral cancer and
other adverse health eects, the research gaps must be
addressed. In this Policy Review we provide recom-
mendations on future directions for betel quid and areca
nut use (panel). Addressing betel quid and areca nut use is
a multidisciplinary challenge, requiring the engagement
of collaborators with diverse scientific expertise. A
balanced and comprehensive mix of economic
interventions (supply and demand reduction strategies
patterned after MPOWER), investments in surveillance
and clinical services, research, and policy considerations
are essential to address the fast-growing burden of oral
cancers associated with betel quid and areca nut products.
Contributors
KD, MP, and ELT developed the concept proposal for the International
Conference on Betel Quid and Areca Nut held in April, 2016, in Kuala
Lumpur, Malaysia. As part of the conference, HM, KD, RBZ, PCP, and
Search strategy and selection criteria
We did a systematic literature search between Feburary, 2016,
and April, 2016, in PubMed and Google Scholar to identify
studies of and all relevant articles on the following topics:
the effective prevention, cessation, and control of betel quid;
screenings for betel quid-related cancers; and policies and the
economic impact of areca nut and betel quid use. We
completed a search for articles published in English using the
following keywords: “areca” OR “betel quid” OR “areca”[title/
abstract] OR “betel nut” OR “betel” OR “gutka” OR “gutkha” OR
“ghutka” OR “paan” [title/abstract] OR “pan masala” OR “khilli
paan” OR “dohra” OR “mawa” OR “mainpuri” OR “tombol”. The
search was not limited by year of publication. We did a
preliminary review of abstracts to identify study relevance.
Studies that met the eligibility criteria were included for
further review of the full-text article. In addition to the
electronic search of keywords, we also searched the reference
list of all identified relevant studies and reviewed articles on
the subject. Additional studies were identified by the authors
and attendees of the International Conference on Betel Quid
and Areca Nut 2016 and incorporated into the Policy Review.
MP planned and coordinated activities for the inaugural conference.
Conference session chairs were identified to contribute to the
identification of key research areas for betel quid and areca nut control.
HM, KD, and MP developed the outline of the report. HM wrote the first
draft of all sections and edited subsequent drafts of the report, including
the final version. MP and KD edited, wrote, and reviewed various
sections of the subsequent draft. All session chairs (AD, ERG, PCG, PCP,
RM, ASAN, C-PW, RBZ) contributed to the recommendations, reviewed
the various sections of a subsequent draft of the report, and approved the
final Policy Review. MP, KD, SW, and ELT did a final review.
Declaration of interests
We declare no competing interests.
Acknowledgments
This Policy Review had no funding or grants. HM, KD, MP, PCP, and
ELT are employed by the US National Institutes of Health (NIH). No
authors have current active US NIH grants. C-PW is supported by the
Taiwan Ministry of Health and Welfare Clinical Trial and Research
Center of Excellence (MOHW104-TDU-B-212-113002), China Medical
University Hospital, Taiwan.
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