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Journal of Cancer Research and Therapeutics, Vol. 3, No. 2, April-June, 2007, pp. 127-130 Epedemiology Impact of Toombak dipping in the etiology of oral cancer: Gender-exclusive hazard in the Sudan Hussain G Ahmed, Rayan M Mahgoob Department of Histopathology and Cytology, Faculty of Medical Laboratory Science, University of Khartoum Code Number: cr07033 Abstract Background : Oral cancer (OC) mortality is very high in Sudan, particularly among men due to the habit of Toombak use (tobacco specific nitrose amine (TSN)) rich tobacco.Aims : Our aim was to determine whether OC is gender-specific due to increased Toombak use among males as suggested a risk for subsequent development of oral cancer. Settings and Design : We conducted a descriptive study of OC in Khartoum and obtained information on Toombak use, confounding variables for 39 incident patients with oral cancerous lesions and 43 hospital-based cases without apparent oral lesions. Materials and Methods : OC was affirmed by histopathology for all patients with oral lesions, hence oral epithelial atypia and leukoplakias were detected using cytology. Statistical Analysis : Data analyzed using a computer SPSS program. Results and Conclusions : Of the 82 subjects, there were 57 (70%) Toombak users and 25 (30%) non-tobacco users. Among the 39 patients with OC, 24 (61.5%) were Toombak users and 15 (38.5%) were non-tobacco users. Among 43 with atypical changes, 10 (23.3%) were non-tobacco users and 33 (76.7%) were Toombak users. Regarding gender, only 11 (13.4%) were females, of whom 8 (72.7%) were non-tobacco users. We conclude that oral cancer, atypia and leukoplakia were high among males who were Toombak users. In view of the high incidence (29%) of OC due to Toombak use, we propose the implementation of oral screening programme restricted to Toombak users. Keywords: Atypia, cytology, Sudan oral cancer, Toombak Introduction The use of Toombak has been stated to play a major role in the etiology of oral cancer in the Sudan and is suspected to be associated with neoplasm of salivary glands. [1],[2],[3] In the Sudan, snuff, locally known as Toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form and its use is widespread in the country. Tobacco used for manufacture of the Toombak is of the species Nicotiana rustica and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8-11, moisture content ranges 6-60% and nicotine content is from 8 to 102 mg/g dry wt and tobacco specific nitrosamines TSNAs contents in micrograms (N′-nitrosonornicotine NNN 420-1 550; 4-(methyl-nitrosamino)-l-(3- pyridyl )-l- butanone NNK 620-7 870; N′-nitrosoanatabine NAT 20-290). [4] Toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. The risk for cancer of the oral cavity among Toombak users was high (RR 7.3-73.0-fold). [5] The use of Toombak plays a significant role in etiology of oral squamous cell carcinomas (OSCCs), with the tobacco specific nitrosamines present in Toombak possibly acting as principal carcinogens. [6],[7],[8] Materials and Methods In this descriptive study, we obtained information on the habit of Toombak use, confounding variables for 39 incident patients with oral cancerous lesions and 43 hospital-based cases without apparent oral lesions. Two specimens type were obtained (Biopsy or cytological smear). All participants were asked to sign a written consent before the taking of the specimen. All consecutive patients with oral cancerous or precancerous lesions were considered for the study. Biopsy : A biopsy was taken from each patient with oral lesion after the surgical operation, then placed in 10% buffered formalin and sent to the laboratory for histopathology. Biopsies of thickness of 5-mm in diameter were selected for tissues required for histopathology. These biopsies were processed in tissue processing machine until paraffin wax embedded blocks were prepared. Sections of 5 µm in thickness were obtained from formalin-fixed paraffin wax embedded tissues using a rotary microtome. Sections were stained using Hematoxylin and Eosin adopting Mayer′s procedure. Cytological smear : Using a flat wooden tongue spatula, cytological smears were collected from all patients without apparent oral lesions. The surface epithelium was scraped and cells were collected, immediately smeared on a cleaned frosted end glass slide, fixed in 95% ethanol for 15 min and then transferred to the laboratory at the Faculty of Medical Laboratory Science, University of Khartoum for further processing. Smears were further treated according to Papanicolaou method. Smears were hydrated in descending ethanol concentrations of 95% through 70% to distilled water, 2 min in each. For nuclear staining, smears were treated with Harris′s Haematoxylin for 5 min, rinsed in distilled water and differentiated in 0.5% aqueous hydrochloric acid for 10 sec to remove excess stain particles and then immediately rinsed in distilled water to stop decoloration. Thereafter, smears were stained blue in alkaline water for 4 sec and dehydrated in ascending ethanol concentrations of 70% through two changes of 95%, 2 min in each. For the cytoplasmic staining, smears were treated with Papanicolaou Orange G6 solution for 2 min, rinsed in 95% ethanol and treated in Papanicolaou EA50 staining solution for 3 min. Finally, the smears were dehydrated in 95% through absolute ethanol, cleared in Xylene and then mounted in the DPX (Distrene Polystyrene Xylene) mount. Results This study investigated 82 study subjects, their ages ranging from 18 to 76 with a mean age of 48 years. Of the 82 studied subjects, 57 (70%) were Toombak users and 25 (30%) were non-Toombak users. Among these 82 participants, 39 (47.6%) were histopathologically confirmed patients as having OC, hence, the remaining 43 (52.4%) were cytologically diagnosed as having atypia 34 (79%) or leukoplakia 9 (21%), as shown in [Table - 1]. As to the 39 patients with OC, 15 (38.5%) were non-tobacco users and 24 (61.5%) were Toombak users. In regard to 43 with cytological atypia or leukoplakia, 10 (23.5%) were non-tobacco users and 33 (76.5%) were Toombak users. These findings reveal a 29% incidence of OC due to Toombak use vs 18% incidence of OC amongst non-Toombak users. In what concerning the site of the lesion among those 39 with OC; of the 24 Toombak users 13 (54.2%) were found with lesions at lower lip (at the site of saffa) followed by buccal mucosa 5 (20.8%) and gingival 4 (16.7%), hence, most of lesions among non-tobacco users were initiated at tongue 5 (33.3%), lower lip 4 (26.7%) and buccal mucosa 3 (20%). Notably, all specimens for diagnosing atypia or leukoplakia were taken from buccal mucosa or lower labia (according to the site of dip in Toombak users or observed changes), as denoted in [Table - 2]. However, the preponderance of lesions were detected at lower lip 17 (39.5%) followed by buccal mucosa 8 (18.6%), tongue 7 (16.3%), gingival 6 (14%). Furthermore, nearly all carcinomas were found at lower lip 17 pursued by buccal mucosa 8 and tongue 7. With reference to the duration of Toombak use, the largest part of cases were found at durations 21-30 years followed by 31+ and 10-20 constituting 22 (39%),19 (33%),14 (24,5%) respectively, as exposed in [Table - 3]. On the other hand, the largest part of the study subjects were males 71(86.6%) and the remaining 11(13.4%) were females. Of the 71 males, 54(76%) were Toombak users yet, the majority of females were non-tobacco users 8(72.3%), as shown in [Table - 3]. Pertaining to the gender and diagnosed conditions, all cases of atypia 34(100%) were males, as indicated in [Table - 4]. Discussion Oral cancer is one of the major health problems in the Sudan, due to the habit of use of Toombak, that is known to contain high level of the potent carcinogenic component of the tobacco (TSN). [9] Therefore, the current study is an attempt to correlate the high incidence (29%) of oral cancer among males to the use of Toombak. Thus, of the 82 patients with oral precancerous and cancerous lesions, 57 (70%) were found to be Toombak users compared to 25(30%) non-tobacco users. Among these 57 individuals only 2 were females. Similar outcomes in the effect of Toombak were previously reported that the use of Toombak plays a major role in the etiology of oral cancer in the Sudan. [3] Toombak was found to be associated with the highest risk for developing oral cancer when compared with other forms of snuff by numerous studies. [5] The increased risk associated with the use of Toombak is of particular concern in view of its wide consumption in the Sudan. [10] Among 62 patients with oral cancer, 50 were Toombak users; the majority of these had tumors at the site of contact with the tobacco or in adjacent areas. Chemical analytical studies revealed that Toombak contains at least 100-fold higher concentrations of the tobacco-specific N-nitrosamines (TSNA) than United States and Swedish commercial snuff brands. [2],[11] Our findings showed a high frequency of OSCs (73%) that have been demonstrated in a number of studies that studied OSCs from Sudanese patients. Squamous-cell carcinoma was reported as the most common oral malignancy (66.5%). [3] In regard to the site of the lesions, most of carcinomas arise at lower lip at the site where Saffa is placed, which was correspondingly reported. [12] Referring to the gender, there were only 11 (13.4%) women in our study, though we included all patients attended to the hospital during the period of the study. However, Toombak use is uncommon among females, as it considered as a social stigma in the Sudan. Therefore, 9 of these 11 cases were non-Toombak users. This is why oral cancer due to Toombak use is gender-specific mostly restricted to men. Similar report previously stated somewhere. [3] Even though, the majority of patients in this study have prolonged history of Toombak use, which reduced the possibility of measuring the period of use, but it seemed that the effect increases with the increasing of duration of use, as indicated in our results. Though oral cancer is a global health problem with increasing incidence and mortality rates, no national population-based screening programmes for oral cancer have been implemented in the Sudan. To date there is debate on whether to employ screening programs for cervical cancer in the daily routine work of health suppliers. However, as 52.4% of the cases (particularly atypia) were diagnosed using exfoliative cytology, this support the implementation of exfoliative cytology as a tool for screening of those at high risk to develop oral cancer (Toombak dippers). Nevertheless, a study indicated the novel application of cytology as a successful contraption in early detection of oral cancerous and precancerous lesions, when applied a retrospective cohort to assess the presence and severity of oral epithelial atypia (ET) in 300 subjects (100 Toombak dippers; 100 cigarette smokers; 100 non-tobacco users). For the ET among Toombak dippers and cigarette smokers, adjusted OR and the 95% CI were found to be 3 (0.91-9.7) and 4 (1.2-12.3), respectively. [13] We conclude that; Toombak use is a major risk factor that responsible of high frequencies of oral cancers and in particular OSCCs in the Sudan. Most of tumors were observed at the site of dip application (lower lip). Oral cancer seems to be gender-specific, as the majority of cases were males. As Toombak use is considered as social stigma among females, these suggesting that there are other risk factors require more investigations, particularly among females. As oral cancer is a major health problem in the Sudan strategy for prevention comprising comprehensive public educational program is high recommended. All those involved in the habit of Toombak use should undergo a continuous screening programme. Exfoliative cytology is the most suitable method for implementation of oral screening program as it is both non-invasive and cheap. Acknowledgements We would like to thank Ali Mahmoud and Shima Osman Department of histopathology and Cytology, Faculty of medical Laboratory Sciences, U of K for their technical help and assistance. We are very grateful to the people at the Toombak and Smoking Research Centre and Dental Teaching Hospital in Khartoum for their technical help and assistance.References
Copyright 2007 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr07033t3.jpg] [cr07033t1.jpg] [cr07033t2.jpg] [cr07033t4.jpg] |
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