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A review of betel quid chewing, oral cancer and precancer in Mainland China
Oral Oncology (2007) 43, 424– 430
available at www.sciencedirect.com
journal homepage: http://intl.elsevierhealth.com/journals/oron/
REVIEW
A review of betel quid chewing, oral cancer and precancer in Mainland China Xiaolin Zhang a, Peter A. Reichart
b,*
a
School and Hospital of Stomatology, Peking University, Beijing, China ´, Department of Oral Surgery and Dental Radiology, Center for Dental Medicine (CC3), Charite ¨tsmedizin Berlin, Campus Virchow Klinikum, CC3 fu ¨r Zahn-, Mund- und Kieferheilkunde, Abteilung fu ¨r Universita ¨rztliche Ro ¨ntgenologie Augustenburger Platz 1, 13353 Berlin, Germany Oralchirurgie und zahna b
Received 28 July 2006; accepted 29 August 2006 Available online 26 January 2007
KEYWORDS
Summary On the Chinese mainland, betel quid (BQ) chewing is common in the Hunan and Hainan provinces. The BQ chewing habit in Hunan consists of dried husks and betel nuts, which are sold as industrially packaged, areca nut-based products. In Hainan, the fresh nut is chewed. Tobacco is not added. Reported prevalence of BQ chewing in Hunan province is high (64.5– 82.7%). Oral diseases associated with BQ chewing are oral submucous fibrosis (OSF), oral leukoplakia (OL) and oral cancer. Reported prevalence of OSF among BQ chewers ranges from 0.9% to 4.7%. People most commonly affected are between the ages of 30 and 39 years, and 40 and 49 years. The reported prevalence of OL in Hainan ranges from 2.1% to 2.5%. In BQ chewers who also smoke, the reported prevalence is 20.3%. The prevalence of OL in Hunan province ranges from 0.1% to 0.5%. The prevalence of oral cancer among BQ chewers is low, ranging from 0.02% to 0.05%. In cases of OSF, reported prevalence is 2.6% and 1.2%. Presently, data on prevalence of BQ chewing in southern provinces of Mainland China is limited. BQ chewing habits, however, seem to differ between geographic areas. Future case–control studies are necessary to evaluate the risk for oral cancer and other associated oral mucosal diseases resulting from variations in BQ chewing habits. c 2006 Elsevier Ltd. All rights reserved.
Betel quid chewing; Oral submucous fibrosis; Oral cancer; Oral leukoplakia; PR China
Introduction
* Corresponding author. Tel.: +49 30 450 56 26 02; fax: + 49 30 450 56 29 01. E-mail address: [email protected] (P.A. Reichart).
The chewing of betel quid (BQ), including Areca catechu L., the betel leaf (Piper betle L.) and lime, is a habit of great antiquity in South and Southeast Asia. It is estimated that 600 million people chew BQ worldwide.1 BQ chewing, with and without tobacco, is carcinogenic.2 The habit is associ-
1368-8375/$ - see front matter c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2006.08.010
A review of betel quid chewing, oral cancer and precancer in Mainland China ated with oral cancer, oral leukoplakia and oral submucous fibrosis (OSF). An extensive number of studies on BQ chewing and associated oral diseases have been published in South and Southeast Asia, including Taiwan. However, little information is available on this habit in Mainland People’s Republic of China. The IARC monograph 852 only refers to two papers in the English language describing studies from the Southern provinces of China.3,4 As so little information is available in the international literature, we aimed to review Chinese language papers on BQ chewing and associated oral diseases in provinces of Mainland China, where BQ chewing is prevalent.
History and characteristics of betel quid chewing in Mainland China Betel (Areca catechu L.) has long been used in traditional Chinese medicine, mainly as an anthelmintic for parasites of the intestinal tract. BQ chewing was probably introduced to China during the Ming dynasty (A.D. 1368–1644). The habit is mainly concentrated in the southern provinces of Mainland China, including the provinces of Hunan, Hainan and Yunnan (Fig. 1).5,6
Betel quid chewing in the province of Hunan The BQ chewing habit of Hunan is different from that of other geographic areas where BQ chewing is prevalent.
425
As betel palms are not grown in the province of Hunan, areca nuts are imported either from Hainan or from Thailand. Dried areca nuts, including the husk, are processed as industrially packaged products. Processing consists of marinating the halved fruits with different flavoured substances. The final products for chewing are half fruits, including the husk in a dried state (Fig. 2).6,7 The nut alone is never chewed.5,7 The BQ is sold in small bags of different brands (Fig. 3). The substances for flavouring are declared on the surfaces of these bags. The following substances may be included: saccharine, malt sugar, edulcorant, cassia oil, peppermint, borneol, gelatin, lime, sodium bicarbonate, calcium carbonate, glacial acetic acid, acetylsulfa and calcium hydroxide. Lime is always used as a main component. Tobacco, however, is never added. Generally, either five or ten to twelve pieces of quid are contained in one bag. The BQ may be divided into large, medium and small sizes, weighing about 3.5, 2.5 and 1.80 g per piece. The chewers never swallow the BQ. Although chewers in Hunan never chew tobacco, some smoke cigarettes or water pipes. Hunan chewers may be divided into three types: occasional chewer (one piece or less a day), habitual chewer (5–10 pieces a day) and heavy chewer (20 pieces a day). The habit of BQ chewing is common in most cities of Hunan, such as Xiangtan, Changsha, Hengyang, Yiyang and Loudi. In one study8 it was revealed that the number of chewers had increased since the 1980s. The study also showed that younger people have started to chew BQ.8
Figure 1 Betel quid chewing habit in Mainland China is prevalent in the provinces of Hunan, Hainan and Yunnan. The habit is also found on the island of Taiwan.
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X. Zhang, P.A. Reichart
Figure 2
The final product for chewing are half areca fruits, showing the husk in a dried state.
Betel quid chewing in the province of Hainan On Hainan island, the fruit is chewed fresh with lime, wrapped in a betel leaf. Tobacco is not added to the quid. Of 100 BQ chewers in the Linshui District of Hainan, 42 chewed BQ alone, 31 chewed BQ and smoked cigarettes, 21 chewed BQ and smoked water pipe and one chewed BQ and smoked cigarettes and a water pipe. Of the 46 women surveyed, 80% chewed areca nut with no additional habit.4 Lin et al.9 studied 4554 individuals from Hainan island, of whom 954 were BQ chewers (20.9%) and 773 individuals were BQ chewers and smokers (16.9%).9
Betel quid chewing in the province of Yunnan No publications in English or Chinese are available on the prevalence and variations of BQ chewing in this province.
Chewing habits and diseases of the oral mucosa Oral submucous fibrosis OSF has been considered to represent ‘‘a localized scleroderma’’, and has been described as such in textbooks in Mainland China.10 The term OSF first appeared in a review article on OSF in the Chinese language in 1981.11 The first cases of OSF were reported by Pindborg et al.4 in 1984, who described three women with clinical and histological features of OSF. In 1985, Jian et al.12 reported two cases of OSF from Hunan province. OSF was observed in two sisters aged 14 and 20 years, who were selling BQ.12
Prevalence studies on betel quid chewing and oral submucous fibrosis Epidemiologic studies on BQ chewing were carried out in Xiangtan13,14 and in Changsha15 of Hunan province in the 1980s and 1990s. Prevalence of BQ chewing was between 64.5% and 82.7%. The prevalence of OSF is shown in Table 1.13–15 One hospital-based study of 278 people with OSF showed that 94.6% were men and 5.4% were women. The ages of the women ranged from 16 to 69 years; mean age 34.5 years). Women aged 30–39 years were most commonly affected.8 Another clinical study of 382 cases with OSF (370 men, 12 women, age range 19–62 years, mean 34.4 years) from Changsha was reported by Tan et al.16 Data of surveys showed that the cheek was most commonly affected by OSF (93.2% and 97.0%), followed by the palate (8.4% and 73.5%), lip (8.1% and 41.2%), glossopalatine arch (1.5% and 29.4%), tongue (0.6% and 35.3%), uvula (0.6% and 32.4%), gums (0.6% and 8.8%),13,14 tonsils (29.4%), floor of the mouth (38.2%)14 and pharyngopalatine arch (1.5%).13 In other studies, the location of OSF8,16 was different. The soft palate and glossopalatine arch were most commonly affected (100%),8 followed by pterygomandibular fold (99.2%),16 cheek (88.8% and 96.3%), soft palate (77.7%), tongue (41.0% and 51.8%), floor of the mouth (41.0% and 18.6%) and lip (35.9%) and uvula (16.2%).8,16 No relation was found between the amount of chewing BQ and the risk for OSF.13,14 Most cases of OSF were found in chewers who chewed BQ for a long period of time.13–15 Three studies described the symptoms and physical signs of cases of OSF. The most common complaint was pain while eating hot food, followed by burning of the oral mucosa or difficulty in opening the mouth. Fibrous bands were the most common physical signs.8,14,16 Jian and Wang17 described changes of the gingiva in 24 cases of OSF. Tang
A review of betel quid chewing, oral cancer and precancer in Mainland China
Figure 3
Table 1
427
Bags of different brands of betel quid as sold in markets of Hunan province.
Prevalence of oral submucous fibrosis in Hunan province
Authors
Individuals (n) Total
Men
Women
Chewers
Men
Tang et al.13 Liu et al.15 Jian et al.14
11.046 5.352 3.642
6.057 – 3.013
4.989 – 629
7.127 4.032 3.015
– – 2.493
et al.18 described changes in the pharynx. In one study, two types of OSF were distinguished: a localized and a diffuse type. The clinical features of the localized type consisted
Age (years)
OSF cases (n)
Prevalence (%)
Women
Mean
Total
Men
Women
– – 522
38.6 – 40.2
335 45 29
252 27 21
83 18 8
4.7 1.1 0.9
of presence of palpable bands in the oral mucosa only. Clinical features of the diffuse type were characterized by burning pain, discomfort, dryness of the oral mucosa,
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X. Zhang, P.A. Reichart
progressive inability to open the mouth and presence of palpable bands in the oral mucosa. The localized type was found in 322 out of 335 cases (96.1%). The diffuse type was observed in 13 cases (3.9%).13 A follow-up study of 59 localized and 13 diffuse types of OSF showed that, over a 10-year follow-up, no change of the clinical type occurred.19 The histological features of OSF described in the Chinese literature correspond to those in the international literature.20,21
Oral leukoplakia Oral leukoplakia (OL) was described by Pindborg et al.4 in a survey of the Hainan province. The prevalence of OL in BQ chewers was 2.1%. Lin et al.9 studied 4554 individuals from Hainan province. The prevalence of OL was 2.5% among 954 BQ chewers and 20.3% in 773 BQ chewers who also smoked (Table 2). The most common site was the lip (53.8%), followed by the cheek (23.2%), commissure (5.9%) and tongue (3.1%).9 The prevalence of OL in BQ chewers in the Hunan province was reported in some surveys. One survey of 7127 BQ chewers reported 36 cases of OL, corresponding to a prevalence of 0.5%.13 In two other surveys of BQ chewers in the Hunan province, a prevalence of OL was found in 0.1% (3015 BQ chewers)14 and 0.1% (4032 BQ chewers).15 The prevalence of OL in cases of OSF was reported in some studies. Among 1166 cases of OSF (984 men, 182 women; age: 12–69 years; mean: 37.6 years),22 74 cases of OL were found, corresponding to a prevalence rate of 6.3%. Other studies reported a prevalence of OL in cases of OSF of 14.9% (n = 19) and 13.3%.15 Generally, the prevalence of OL in cases of OSF from Hunan province was higher
Table 2 chewers
Prevalence of oral leukoplakia among betel quid
Authors
Province
Prevalence (%)
Pindborg et al.4 Lin et al.9 Tang et al.13 Jian et al.14 Liu et al.15
Hainan Hainan Hunan Hunan Hunan
2.1 2.5 0.5 0.1 0.1
Table 3
compared with the prevalence of OL in non-OSF cases (2.7%).20
Oral lichen planus The prevalence of oral lichen planus (OLP) in BQ chewers in Hunan was 0.1%,13 0.1%14 and 0.15%.15 The prevalence of OLP in cases of OSF in Hunan was 3.2%,22 1.3%,16 2.4%,13 and 5.9%.20 The prevalence of OLP in cases of OSF in Hunan province studies was higher than the prevalence of OLP in non-OSF cases, which was 0.2%.20
Oral cancer Cases of oral cancer with and without OSF were reported in epidemiologic13–15 and clinical studies.22,23 Generally, the prevalence of oral cancer in BQ chewers and OSF cases was low (Table 3).13–15,22,23 Liu et al.15 reported a case of a man with oral cancer who chewed BQ and smoked for more than 20 years. Gao et al.22 identified 20 individuals with oral cancer who chewed between 5 and 20 pieces of BQ a day (mean: 12 pieces), and had been chewing for 10–40 years (mean: 17 years). Of the 20 individuals with oral cancer, 18 were cigarette smokers. The cheek was the most commonly affected site (85%). The combined habits of BQ chewing and smoking were considered serious risk factors for oral cancer.22 In another study by Jian et al.,23 three cases of oral cancer were found (cheek two cases, tongue one case). More than 10 pieces of BQ were chewed per day over a period of 13 years. Two patients smoked more than 20 cigarettes per day. The third case was that of a man smoking dried tobacco leaf with a Chinese style pipe. He smoked about 500 g of dried tobacco a month.23 Another case of oral cancer associated with OSF was reported from Yiyang (Hunan). The man chewed more than 10 pieces of BQ per day over a period of more than 40 years. He also smoked 500 g of a special tobacco called ‘‘Hanyan’’ a month.24
Discussion and conclusions The published literature on BQ chewing and associated oral precancer and oral cancer is extensive for most geographic areas where BQ chewing is prevalent, including Taiwan and South and Southeast Asia; however, information about BQ chewing in Mainland China is limited. This review of BQ chewing and associated oral lesions yielded only 22 studies,
Oral cancer in betel quid chewers and oral submucous fibrosis cases
Authors
BQ chewers (n)
OSF cases (n/%)
Oral cancer cases (n)
Prevalence (%) In BQ Chewers
13
Tang et al. Jian et al.14 Liu et al.15 Gao et al.22 Jian et al.23
7.127 3.015 4.032 – –
Total
Men
Women
Total
Men
Women
335/ 4.7 29/ 0.9 45/ 1.1 1.166 147
252 21 27 984 125
83 8 18 182 22
4 0 1 20 3
3 0 1 18 3
1 0 0 2 0
BQ, betel quid; OSF, oral submucous fibrosis.
0.05 0 0.02 – –
In OSF cases Total
Men
Women
1.2 0 2.2 1.7 2.0
1.2 0 3.7 1.8 2.4
1.2 0 0 1.1 0
A review of betel quid chewing, oral cancer and precancer in Mainland China most of which were published in the Chinese language. This fact alone makes it difficult for the international research community interested in BQ chewing habits and their association with oral diseases to evaluate the situation in Mainland China. In this review, we reveal several unknown aspects of BQ chewing as practiced in some southern provinces of Mainland China. Chewing habits differ in the provinces of Hainan and Hunan. In Hainan, the fresh areca nut is chewed, because areca palms are grown on the island; in Hunan province, the dried areca nut, including the husk, is preferred. Data from the province of Yunnan are not available, although BQ chewing is also found in this province, particularly in the area bordering Myanmar.25 In Hunan province, industrially packaged areca nuts are available unlike Pan Masala and Guthka in India and neighbouring countries such as Myanmar.25 In countries where these products (Pan Masala, Guthka) are available, scientists have warned of an emerging threat to health (OSF, oral cancer).26 Whether the industrial areca nut products made in Hunan province have the same deleterious effects as Pan Masala or Guthka is not yet known. The prevalence of oral cancer, however, seems to be much lower than that associated with Pan Masala and Guthka.2 The fact that the Hunan betel quid also contains husk is unusual and, to our knowledge, is probably the only geographic area that includes the quid. Although most constituents of the betel quid have been examined and analyzed, particularly relating to the areca nut derived nitrosamines,2 the husk has not undergone the same analytic procedures as the betel leaf, the areca nut and other constituents.2 This fact alone causes significant difficulties in evaluating the role of the husk in the aetiology of oral mucosal lesions. Of interest further, is that the habit of BQ chewing of Hainan and Hunan are different from those in Taiwan. In Taiwan, the fresh areca nut is chewed with slaked lime and betel inflorescence, sometimes wrapped in betel leaf. Tobacco is not added. About 10% of the population, including adolescents, chew areca nut, with the highest usage among men (90%). According to a recent IARC Monograph,2 about one-third of the population of Hainan (both women and men) use areca nut, indicating a higher prevalence compared with Taiwan. The present review, however, has shown that the prevalence of BQ-chewing in Hunan province was rather high (64.5–82.7%). As information on representativeness of registry data, including validity, accuracy and reliability, was unavailable for some of these studies, it is difficult to compare these data with those of other geographic areas. The studies reviewed in this paper represent cohort or hospital-based studies, and it has been stated that the risk for oral cancer is increased if the BQ chewing habit is combined with smoking.22 Future case–control studies, including statistical significance of risk for oral cancer and other oral mucosal diseases after stratification for smoking and alcohol use, are warranted. According to the studies reviewed in this paper, the prevalence of oral cancer in Mainland China seems to be low compared with cross-sectional surveys of oral cancer in India and Southeast Asia.2 This difference might be explained by the difference in composition of the betel quid, particularly that of Hunan province. As no studies on dose–response are presently available, it is difficult to explain the rather low prevalence figures for oral cancer in Chinese Mainland. Oral submucous fibrosis, on the other hand, was
429
found with prevalence figures between 0.9% and 4.7%. In comparison, prevalence of OSF from five geographic areas of India varied between 0.05% and 1.4%.2 Compared with these figures, prevalence figures of OSF for Mainland China seem to be higher. No explanation can be given for this phenomenon on the basis of this review article. This review of the literature provides an insight into the differences in BQ chewing habits in Mainland China compared with Taiwan and other areas where BQ chewing is prevalent. However, few data are available to draw conclusions on the dose relationship and risk analysis of these BQ chewing habits in this part of the world. Case–control studies are necessary to obtain more precise data on the risk of oral cancer and associated precancerous lesions, including OL and OSF.
References 1. Reichart PA, Philipsen HP. Betel and Miang. Vanishing Thai habits. 2nd ed. Bangkok: White Lotus Ltd. Co; 2005. 2. World Health Organization, International Agency for Research on CancerIARC Monograph on the evaluation of carcinogenic risks to humans. Betel-quid and Areca-nut chewing and some Areca-nut-derived nitrosamines, vol. 85. Lyon, France: IARC; 2004. 3. Tang JG, Jian XF, Gao ML, Ling TY, Zhang KH. Epidemiological survey of oral submucous fibrosis in Xiangtan City, Hunan province, China. Community Dent Oral Epidemiol 1997;25:177–80. 4. Pindborg JJ, Zheng KH, Kong FX, Lin CR. Pilot survey of oral mucosa in areca (betel) nut chewers on Hainan island of the People’s Republic of China. Commun Dent Oral Epidemiol 1984;12:195–6. 5. Liu SF, Shen ZH, Tang ZG, Su HB, Luo CF. On treatment of oral submucous fibrosis with glucosidorum tripterygii totorum. Beijing J Stomatol 1999;7:167–9. [in Chinese]. 6. Wu MS, Tang LD. Interference of betel quid chewing with the therapy of duodenal ulcer. China J Modern Med 1998;8:45–7. [in Chinese]. 7. Lei RC, Jian XC. The habit of chewing betel and oral submucous fibrosis. Chin J Clin Rehabil 2005;9:24–5. [in Chinese]. 8. Gao YJ, Ling TY, Liu L, Li WH, Li X. Epidemiological change of oral submucous fibrosis: a retrospective a study of 278 cases. J Clin Stomatol 2004;20:117–9. [in Chinese]. 9. Lin FX, Kong QR, Lin TC. An epidemiologic study of oral leukoplakia in Hainan island. Chin J Stomatol 1985;20:180–2. [in Chinese]. 10. Wu QG. Oral histology and pathology. Beijing: People’s Medical Publishing House; 1979., p. 117–8. [in Chinese]. 11. Zhang XL, Wu QG. Oral submucous fibrosis: a review. Fascicle of stomatology. J Foreign Med Sci 1981;8:212–6. [in Chinese]. 12. Jian XC, Shen ZH, Liu SF. Oral submucous fibrosis – case reports. J Clin Stomatol 1985;1:12–3. [in Chinese]. 13. Tang JQ, Zhu ZT, Ling TY, Gao ML, Jian XF. A study of 335 cases of oral submucous fibrosis. West China J Stomatol 1993;11:130–2. [in Chinese]. 14. Jian XC, Liu SF, Shen ZH, Cheng HB. A clinical study of oral submucous fibrosis. Chin J Stomatol 1989;24:299–302. [in Chinese]. 15. Liu SF, Jian XC, Shen ZH. A study of oral submucous fibrosis. J Clin Stomatol 1988;4:81–3. [in Chinese]. 16. Tan H, Xie H. The clinical analysis of oral submucous fibrosis. J Oral Sci Res 2004;20:529–31. [in Chinese]. 17. Jian XC, Wang SZ. Pathological changes of the gums in oral submucous fibrosis. J Oral Sci Res 2001;17:231. 18. Tang JQ, Ling TY. Laryngoscopic findings in 8 cases of oral submucous fibrosis. J Stomatol 1997;17:37–8. [in Chinese].
430 19. Gao YJ, Ling TY, Tang JQ. A Study on the clinical classification of oral submucous fibrosis. West China J Stomatol 2000;18:250–1, and 258. [in Chinese]. 20. Gao ML, Tang JQ, Zhu ZT, Jian XF. A pathological study of oral submucous fibrosis. Chin J Stomatol 1990;25:363–5. [in Chinese]. 21. Jian XC, Liu SF, Shen ZH, Yang YH. Histomorphologic observations on epithelial tissue of 24 cases of oral submucous fibrosis. West China J Stomatol 1988;6:227–9. [in Chinese]. 22. Gao YJ, Ling TY, Yin XM, Yao ZG, Tang JQ. A retrospective study of malignant transformation of oral submucous fibrosis. J Clin Stomatol 2005;21:119–20. [in Chinese].
X. Zhang, P.A. Reichart 23. Jian XC, Peng JY, Tang ZG, Shen Q, Su T. Three cases of oral cancer associated with oral submucous fibrosis. West China J Stomatol 2000;18:130–1. [in Chinese]. 24. Zhang Y, Jian XC, Liu SF, Peng JY, Shen ZH. A case of oral cancer in oral submucous fibrosis – case report. J Clin Stomatol 1990;6:118–9. [in Chinese]. 25. Reichart PA, Way TH. Oral cancer and pre-cancer in Myanmar: a short review. J Oral Pathol Med 2006;35:193–6. 26. Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes guthka and pan masala: a review of agents and causative mechanisms. Mutagenesis 2004;19:251–62.
available at www.sciencedirect.com
journal homepage: http://intl.elsevierhealth.com/journals/oron/
REVIEW
A review of betel quid chewing, oral cancer and precancer in Mainland China Xiaolin Zhang a, Peter A. Reichart
b,*
a
School and Hospital of Stomatology, Peking University, Beijing, China ´, Department of Oral Surgery and Dental Radiology, Center for Dental Medicine (CC3), Charite ¨tsmedizin Berlin, Campus Virchow Klinikum, CC3 fu ¨r Zahn-, Mund- und Kieferheilkunde, Abteilung fu ¨r Universita ¨rztliche Ro ¨ntgenologie Augustenburger Platz 1, 13353 Berlin, Germany Oralchirurgie und zahna b
Received 28 July 2006; accepted 29 August 2006 Available online 26 January 2007
KEYWORDS
Summary On the Chinese mainland, betel quid (BQ) chewing is common in the Hunan and Hainan provinces. The BQ chewing habit in Hunan consists of dried husks and betel nuts, which are sold as industrially packaged, areca nut-based products. In Hainan, the fresh nut is chewed. Tobacco is not added. Reported prevalence of BQ chewing in Hunan province is high (64.5– 82.7%). Oral diseases associated with BQ chewing are oral submucous fibrosis (OSF), oral leukoplakia (OL) and oral cancer. Reported prevalence of OSF among BQ chewers ranges from 0.9% to 4.7%. People most commonly affected are between the ages of 30 and 39 years, and 40 and 49 years. The reported prevalence of OL in Hainan ranges from 2.1% to 2.5%. In BQ chewers who also smoke, the reported prevalence is 20.3%. The prevalence of OL in Hunan province ranges from 0.1% to 0.5%. The prevalence of oral cancer among BQ chewers is low, ranging from 0.02% to 0.05%. In cases of OSF, reported prevalence is 2.6% and 1.2%. Presently, data on prevalence of BQ chewing in southern provinces of Mainland China is limited. BQ chewing habits, however, seem to differ between geographic areas. Future case–control studies are necessary to evaluate the risk for oral cancer and other associated oral mucosal diseases resulting from variations in BQ chewing habits. c 2006 Elsevier Ltd. All rights reserved.
Betel quid chewing; Oral submucous fibrosis; Oral cancer; Oral leukoplakia; PR China
Introduction
* Corresponding author. Tel.: +49 30 450 56 26 02; fax: + 49 30 450 56 29 01. E-mail address: [email protected] (P.A. Reichart).
The chewing of betel quid (BQ), including Areca catechu L., the betel leaf (Piper betle L.) and lime, is a habit of great antiquity in South and Southeast Asia. It is estimated that 600 million people chew BQ worldwide.1 BQ chewing, with and without tobacco, is carcinogenic.2 The habit is associ-
1368-8375/$ - see front matter c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2006.08.010
A review of betel quid chewing, oral cancer and precancer in Mainland China ated with oral cancer, oral leukoplakia and oral submucous fibrosis (OSF). An extensive number of studies on BQ chewing and associated oral diseases have been published in South and Southeast Asia, including Taiwan. However, little information is available on this habit in Mainland People’s Republic of China. The IARC monograph 852 only refers to two papers in the English language describing studies from the Southern provinces of China.3,4 As so little information is available in the international literature, we aimed to review Chinese language papers on BQ chewing and associated oral diseases in provinces of Mainland China, where BQ chewing is prevalent.
History and characteristics of betel quid chewing in Mainland China Betel (Areca catechu L.) has long been used in traditional Chinese medicine, mainly as an anthelmintic for parasites of the intestinal tract. BQ chewing was probably introduced to China during the Ming dynasty (A.D. 1368–1644). The habit is mainly concentrated in the southern provinces of Mainland China, including the provinces of Hunan, Hainan and Yunnan (Fig. 1).5,6
Betel quid chewing in the province of Hunan The BQ chewing habit of Hunan is different from that of other geographic areas where BQ chewing is prevalent.
425
As betel palms are not grown in the province of Hunan, areca nuts are imported either from Hainan or from Thailand. Dried areca nuts, including the husk, are processed as industrially packaged products. Processing consists of marinating the halved fruits with different flavoured substances. The final products for chewing are half fruits, including the husk in a dried state (Fig. 2).6,7 The nut alone is never chewed.5,7 The BQ is sold in small bags of different brands (Fig. 3). The substances for flavouring are declared on the surfaces of these bags. The following substances may be included: saccharine, malt sugar, edulcorant, cassia oil, peppermint, borneol, gelatin, lime, sodium bicarbonate, calcium carbonate, glacial acetic acid, acetylsulfa and calcium hydroxide. Lime is always used as a main component. Tobacco, however, is never added. Generally, either five or ten to twelve pieces of quid are contained in one bag. The BQ may be divided into large, medium and small sizes, weighing about 3.5, 2.5 and 1.80 g per piece. The chewers never swallow the BQ. Although chewers in Hunan never chew tobacco, some smoke cigarettes or water pipes. Hunan chewers may be divided into three types: occasional chewer (one piece or less a day), habitual chewer (5–10 pieces a day) and heavy chewer (20 pieces a day). The habit of BQ chewing is common in most cities of Hunan, such as Xiangtan, Changsha, Hengyang, Yiyang and Loudi. In one study8 it was revealed that the number of chewers had increased since the 1980s. The study also showed that younger people have started to chew BQ.8
Figure 1 Betel quid chewing habit in Mainland China is prevalent in the provinces of Hunan, Hainan and Yunnan. The habit is also found on the island of Taiwan.
426
X. Zhang, P.A. Reichart
Figure 2
The final product for chewing are half areca fruits, showing the husk in a dried state.
Betel quid chewing in the province of Hainan On Hainan island, the fruit is chewed fresh with lime, wrapped in a betel leaf. Tobacco is not added to the quid. Of 100 BQ chewers in the Linshui District of Hainan, 42 chewed BQ alone, 31 chewed BQ and smoked cigarettes, 21 chewed BQ and smoked water pipe and one chewed BQ and smoked cigarettes and a water pipe. Of the 46 women surveyed, 80% chewed areca nut with no additional habit.4 Lin et al.9 studied 4554 individuals from Hainan island, of whom 954 were BQ chewers (20.9%) and 773 individuals were BQ chewers and smokers (16.9%).9
Betel quid chewing in the province of Yunnan No publications in English or Chinese are available on the prevalence and variations of BQ chewing in this province.
Chewing habits and diseases of the oral mucosa Oral submucous fibrosis OSF has been considered to represent ‘‘a localized scleroderma’’, and has been described as such in textbooks in Mainland China.10 The term OSF first appeared in a review article on OSF in the Chinese language in 1981.11 The first cases of OSF were reported by Pindborg et al.4 in 1984, who described three women with clinical and histological features of OSF. In 1985, Jian et al.12 reported two cases of OSF from Hunan province. OSF was observed in two sisters aged 14 and 20 years, who were selling BQ.12
Prevalence studies on betel quid chewing and oral submucous fibrosis Epidemiologic studies on BQ chewing were carried out in Xiangtan13,14 and in Changsha15 of Hunan province in the 1980s and 1990s. Prevalence of BQ chewing was between 64.5% and 82.7%. The prevalence of OSF is shown in Table 1.13–15 One hospital-based study of 278 people with OSF showed that 94.6% were men and 5.4% were women. The ages of the women ranged from 16 to 69 years; mean age 34.5 years). Women aged 30–39 years were most commonly affected.8 Another clinical study of 382 cases with OSF (370 men, 12 women, age range 19–62 years, mean 34.4 years) from Changsha was reported by Tan et al.16 Data of surveys showed that the cheek was most commonly affected by OSF (93.2% and 97.0%), followed by the palate (8.4% and 73.5%), lip (8.1% and 41.2%), glossopalatine arch (1.5% and 29.4%), tongue (0.6% and 35.3%), uvula (0.6% and 32.4%), gums (0.6% and 8.8%),13,14 tonsils (29.4%), floor of the mouth (38.2%)14 and pharyngopalatine arch (1.5%).13 In other studies, the location of OSF8,16 was different. The soft palate and glossopalatine arch were most commonly affected (100%),8 followed by pterygomandibular fold (99.2%),16 cheek (88.8% and 96.3%), soft palate (77.7%), tongue (41.0% and 51.8%), floor of the mouth (41.0% and 18.6%) and lip (35.9%) and uvula (16.2%).8,16 No relation was found between the amount of chewing BQ and the risk for OSF.13,14 Most cases of OSF were found in chewers who chewed BQ for a long period of time.13–15 Three studies described the symptoms and physical signs of cases of OSF. The most common complaint was pain while eating hot food, followed by burning of the oral mucosa or difficulty in opening the mouth. Fibrous bands were the most common physical signs.8,14,16 Jian and Wang17 described changes of the gingiva in 24 cases of OSF. Tang
A review of betel quid chewing, oral cancer and precancer in Mainland China
Figure 3
Table 1
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Bags of different brands of betel quid as sold in markets of Hunan province.
Prevalence of oral submucous fibrosis in Hunan province
Authors
Individuals (n) Total
Men
Women
Chewers
Men
Tang et al.13 Liu et al.15 Jian et al.14
11.046 5.352 3.642
6.057 – 3.013
4.989 – 629
7.127 4.032 3.015
– – 2.493
et al.18 described changes in the pharynx. In one study, two types of OSF were distinguished: a localized and a diffuse type. The clinical features of the localized type consisted
Age (years)
OSF cases (n)
Prevalence (%)
Women
Mean
Total
Men
Women
– – 522
38.6 – 40.2
335 45 29
252 27 21
83 18 8
4.7 1.1 0.9
of presence of palpable bands in the oral mucosa only. Clinical features of the diffuse type were characterized by burning pain, discomfort, dryness of the oral mucosa,
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X. Zhang, P.A. Reichart
progressive inability to open the mouth and presence of palpable bands in the oral mucosa. The localized type was found in 322 out of 335 cases (96.1%). The diffuse type was observed in 13 cases (3.9%).13 A follow-up study of 59 localized and 13 diffuse types of OSF showed that, over a 10-year follow-up, no change of the clinical type occurred.19 The histological features of OSF described in the Chinese literature correspond to those in the international literature.20,21
Oral leukoplakia Oral leukoplakia (OL) was described by Pindborg et al.4 in a survey of the Hainan province. The prevalence of OL in BQ chewers was 2.1%. Lin et al.9 studied 4554 individuals from Hainan province. The prevalence of OL was 2.5% among 954 BQ chewers and 20.3% in 773 BQ chewers who also smoked (Table 2). The most common site was the lip (53.8%), followed by the cheek (23.2%), commissure (5.9%) and tongue (3.1%).9 The prevalence of OL in BQ chewers in the Hunan province was reported in some surveys. One survey of 7127 BQ chewers reported 36 cases of OL, corresponding to a prevalence of 0.5%.13 In two other surveys of BQ chewers in the Hunan province, a prevalence of OL was found in 0.1% (3015 BQ chewers)14 and 0.1% (4032 BQ chewers).15 The prevalence of OL in cases of OSF was reported in some studies. Among 1166 cases of OSF (984 men, 182 women; age: 12–69 years; mean: 37.6 years),22 74 cases of OL were found, corresponding to a prevalence rate of 6.3%. Other studies reported a prevalence of OL in cases of OSF of 14.9% (n = 19) and 13.3%.15 Generally, the prevalence of OL in cases of OSF from Hunan province was higher
Table 2 chewers
Prevalence of oral leukoplakia among betel quid
Authors
Province
Prevalence (%)
Pindborg et al.4 Lin et al.9 Tang et al.13 Jian et al.14 Liu et al.15
Hainan Hainan Hunan Hunan Hunan
2.1 2.5 0.5 0.1 0.1
Table 3
compared with the prevalence of OL in non-OSF cases (2.7%).20
Oral lichen planus The prevalence of oral lichen planus (OLP) in BQ chewers in Hunan was 0.1%,13 0.1%14 and 0.15%.15 The prevalence of OLP in cases of OSF in Hunan was 3.2%,22 1.3%,16 2.4%,13 and 5.9%.20 The prevalence of OLP in cases of OSF in Hunan province studies was higher than the prevalence of OLP in non-OSF cases, which was 0.2%.20
Oral cancer Cases of oral cancer with and without OSF were reported in epidemiologic13–15 and clinical studies.22,23 Generally, the prevalence of oral cancer in BQ chewers and OSF cases was low (Table 3).13–15,22,23 Liu et al.15 reported a case of a man with oral cancer who chewed BQ and smoked for more than 20 years. Gao et al.22 identified 20 individuals with oral cancer who chewed between 5 and 20 pieces of BQ a day (mean: 12 pieces), and had been chewing for 10–40 years (mean: 17 years). Of the 20 individuals with oral cancer, 18 were cigarette smokers. The cheek was the most commonly affected site (85%). The combined habits of BQ chewing and smoking were considered serious risk factors for oral cancer.22 In another study by Jian et al.,23 three cases of oral cancer were found (cheek two cases, tongue one case). More than 10 pieces of BQ were chewed per day over a period of 13 years. Two patients smoked more than 20 cigarettes per day. The third case was that of a man smoking dried tobacco leaf with a Chinese style pipe. He smoked about 500 g of dried tobacco a month.23 Another case of oral cancer associated with OSF was reported from Yiyang (Hunan). The man chewed more than 10 pieces of BQ per day over a period of more than 40 years. He also smoked 500 g of a special tobacco called ‘‘Hanyan’’ a month.24
Discussion and conclusions The published literature on BQ chewing and associated oral precancer and oral cancer is extensive for most geographic areas where BQ chewing is prevalent, including Taiwan and South and Southeast Asia; however, information about BQ chewing in Mainland China is limited. This review of BQ chewing and associated oral lesions yielded only 22 studies,
Oral cancer in betel quid chewers and oral submucous fibrosis cases
Authors
BQ chewers (n)
OSF cases (n/%)
Oral cancer cases (n)
Prevalence (%) In BQ Chewers
13
Tang et al. Jian et al.14 Liu et al.15 Gao et al.22 Jian et al.23
7.127 3.015 4.032 – –
Total
Men
Women
Total
Men
Women
335/ 4.7 29/ 0.9 45/ 1.1 1.166 147
252 21 27 984 125
83 8 18 182 22
4 0 1 20 3
3 0 1 18 3
1 0 0 2 0
BQ, betel quid; OSF, oral submucous fibrosis.
0.05 0 0.02 – –
In OSF cases Total
Men
Women
1.2 0 2.2 1.7 2.0
1.2 0 3.7 1.8 2.4
1.2 0 0 1.1 0
A review of betel quid chewing, oral cancer and precancer in Mainland China most of which were published in the Chinese language. This fact alone makes it difficult for the international research community interested in BQ chewing habits and their association with oral diseases to evaluate the situation in Mainland China. In this review, we reveal several unknown aspects of BQ chewing as practiced in some southern provinces of Mainland China. Chewing habits differ in the provinces of Hainan and Hunan. In Hainan, the fresh areca nut is chewed, because areca palms are grown on the island; in Hunan province, the dried areca nut, including the husk, is preferred. Data from the province of Yunnan are not available, although BQ chewing is also found in this province, particularly in the area bordering Myanmar.25 In Hunan province, industrially packaged areca nuts are available unlike Pan Masala and Guthka in India and neighbouring countries such as Myanmar.25 In countries where these products (Pan Masala, Guthka) are available, scientists have warned of an emerging threat to health (OSF, oral cancer).26 Whether the industrial areca nut products made in Hunan province have the same deleterious effects as Pan Masala or Guthka is not yet known. The prevalence of oral cancer, however, seems to be much lower than that associated with Pan Masala and Guthka.2 The fact that the Hunan betel quid also contains husk is unusual and, to our knowledge, is probably the only geographic area that includes the quid. Although most constituents of the betel quid have been examined and analyzed, particularly relating to the areca nut derived nitrosamines,2 the husk has not undergone the same analytic procedures as the betel leaf, the areca nut and other constituents.2 This fact alone causes significant difficulties in evaluating the role of the husk in the aetiology of oral mucosal lesions. Of interest further, is that the habit of BQ chewing of Hainan and Hunan are different from those in Taiwan. In Taiwan, the fresh areca nut is chewed with slaked lime and betel inflorescence, sometimes wrapped in betel leaf. Tobacco is not added. About 10% of the population, including adolescents, chew areca nut, with the highest usage among men (90%). According to a recent IARC Monograph,2 about one-third of the population of Hainan (both women and men) use areca nut, indicating a higher prevalence compared with Taiwan. The present review, however, has shown that the prevalence of BQ-chewing in Hunan province was rather high (64.5–82.7%). As information on representativeness of registry data, including validity, accuracy and reliability, was unavailable for some of these studies, it is difficult to compare these data with those of other geographic areas. The studies reviewed in this paper represent cohort or hospital-based studies, and it has been stated that the risk for oral cancer is increased if the BQ chewing habit is combined with smoking.22 Future case–control studies, including statistical significance of risk for oral cancer and other oral mucosal diseases after stratification for smoking and alcohol use, are warranted. According to the studies reviewed in this paper, the prevalence of oral cancer in Mainland China seems to be low compared with cross-sectional surveys of oral cancer in India and Southeast Asia.2 This difference might be explained by the difference in composition of the betel quid, particularly that of Hunan province. As no studies on dose–response are presently available, it is difficult to explain the rather low prevalence figures for oral cancer in Chinese Mainland. Oral submucous fibrosis, on the other hand, was
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found with prevalence figures between 0.9% and 4.7%. In comparison, prevalence of OSF from five geographic areas of India varied between 0.05% and 1.4%.2 Compared with these figures, prevalence figures of OSF for Mainland China seem to be higher. No explanation can be given for this phenomenon on the basis of this review article. This review of the literature provides an insight into the differences in BQ chewing habits in Mainland China compared with Taiwan and other areas where BQ chewing is prevalent. However, few data are available to draw conclusions on the dose relationship and risk analysis of these BQ chewing habits in this part of the world. Case–control studies are necessary to obtain more precise data on the risk of oral cancer and associated precancerous lesions, including OL and OSF.
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