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Primary malignant tumors of orofacial region at Benghazi, Libya: A 17 years review
Cancer Epidemiology 33 (2009) 332–336
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Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Primary malignant tumors of orofacial region at Benghazi, Libya: A 17 years review Krishnaraj Subhashraj a,*, Maraai Orafi a, K.V. Nair a, Rafa El-Gehani a, Mohammed Elarbi b a b
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Al-Arab Medical Science University, Benghazi, Libya Department of Oral and Maxillofacial Surgery, Al-Fatah University, Tripoli, Libya
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 19 October 2009
The aim of this study was to systematically analyze the clinical presentations of orofacial malignant tumors in a Libyan population over a period of 17 years and compare the results with the reports from other countries. During the study period, tumors of epithelial origin were found in 160 patients (82%), followed by tumors of immune system, 22 (11%) and tumors of mesenchymal origin, 14 (7%). Of the total malignant tumors, 115 were men and 81 were women and the male to female ratio was 1.41:1. Malignant non-odontogenic tumors were seen in 194 patients (99%) and malignant odontogenic tumors were seen in 2 patients (1%). Among the epithelial tumors, squamous cell carcinoma (50.6%) was the most common neoplasm, followed by mucoepidermoid carcinoma (15%) and adenoid cystic carcinoma (8.7%). The incidence of oral malignancy is impressively low with respect to the corresponding levels in other countries in Africa and some European countries. ß 2009 Elsevier Ltd. All rights reserved.
Keywords: Malignant tumors Squamous cell carcinoma Orofacial Incidence Tongue Floor of the mouth
1. Introduction Cancers of the mouth and oropharynx are the sixth most common malignancy globally [1]. Epidemiology shows that head and neck cancers constitute between 5% and 50% of all cancers, while the orofacial region is found to be the commonest site [2]. It poses a serious health problem for the patient, a challenge for the surgeon and a burden for the society. The incidence of oral cancer shows huge geographic variation, from as low as 1–2% of all malignant tumors in Japan, to around 50% in India [2]. Although the incidence of oral cancer is relatively low (2–6%) in Western countries, there has been a recent dramatic increase in the mortality rate in some European countries [3–8]. There have been only few reports published on malignant neoplasms of the orofacial region from the African continent [9– 11]. Till date, no epidemiological studies on malignant tumors of the orofacial region have been done in Libya, except one study on intraoral minor salivary gland tumors [12]. Knowledge on the incidence of malignant tumors of orofacial region is vital for better understanding of the biology of the disease and for proper diagnosis, treatment and prevention. The purpose of this study was to systematically analyze the clinical presentations of orofacial malignant tumors in a Libyan
* Corresponding author. Tel.: +218 913681026. E-mail addresses: [email protected], [email protected] (K. Subhashraj). 1877-7821/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.canep.2009.10.009
population seen over a period of 17 years and compare the results with the reports from other countries. This paper could be of good clinical importance in assessing all the risk factors in addition to the genetic and environmental influences, because of the fact that although Libya is geographically in the continent of Africa, it has an ethnic population of Arabs. 2. Materials and methods This retrospective study was carried out at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Garyounis University, Benghazi, Libyan Arab Jamahiriya. Libya is located in Northern Africa, bordering the Mediterranean Sea, between Egypt and Tunisia. While Tripoli is the capital of Libya, Benghazi is the second largest city in the country. The faculty of Dentistry at Benghazi was established in 1977 and since then it serves as the only referral center for maxillofacial trauma and pathology for the population of eastern Libya. Libya has an estimated population of about 6.03 million, and the life expectancy at birth of 76.88 years. About 97% of the populations are Arab and Berber and most of them are Muslims [13]. The medical reports and biopsy files of patients who underwent biopsy in the maxillofacial region for various reasons between January 1991 and December 2007 were retrieved from the Department of Oral and Maxillofacial Pathology. For all the cases, the clinical records were re-examined by the authors and the histological sections were also re-confirmed by two senior staffs from the Department of Pathology. The following were the
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
exclusion criteria: incomplete clinical data, reports with doubtful or controversial diagnosis, those with metastatic tumors and reports of non-Libyan nationals. The primary malignant tumors were broadly classified into three categories: tumors of epithelial origin, tumors of mesenchymal origin and tumors of the immune system. Information about age, sex, tumor location and histological type were obtained from each record. Age adjusted standardized incidence rates of squamous cell carcinoma (SCC) were calculated by using the direct method and the world standard population expressed per 100,000 persons using the standard 10-year age divisions. Thus the incidence rates are compared with data from other countries. The population of eastern Libya in 2005 was estimated to be 2.1 million, which is about slightly more than one third of total population of Libya. The patients seen here are thus fairly representative of the Libyan population. The purpose of this study was intended to provide information to health professionals and health authorities, which could be used for community education, diagnosis, early treatment and research. Data was analyzed using the SPSS for Microsoft Windows (version 13; SPSS, Chicago, Ill) statistical software package. Descriptive statistics and test of significance were used as appropriate. The critical level of significance was set at P < 0.05. 3. Results During a period of 17 years, we reviewed the files of 2390 patients who underwent biopsy for various reasons in the orofacial region. Of the total 2390 patients who underwent biopsy in maxillofacial region at our center, 906 (38%) patients had inflammatory and reactive diseases, 432 (18%) had developmental and inflammatory cysts, 405 (16%) had benign odontogenic and non-odontogenic tumors, 196 (8%) had primary malignant tumors, 138 (6%) had premalignant epithelial lesions of mucosa and skin, 89 (4%) had immune based diseases, 7 (<1%) had metastatic tumors and 217 (9%) were grouped as miscellaneous (developmental disturbances, gingival hyperplasia, non-neoplastic salivary gland diseases, etc.). The malignant tumors of orofacial region were broadly classified into three groups: tumors of epithelial region, tumors of mesenchymal region and tumors of the immune system. The relative frequency of different types of primary malignant tumors was classified according to the histological classification, age, gender and location. During the study period, tumors of epithelial origin were found in 160 patients (82%), followed by tumors of immune system, 22
333
(11%) and tumors of mesenchymal origin, 14 (7%). Of the total malignant tumors, 115 were men and 81 were women and a male to female ratio of 1.41:1. The mean age of the patients in both the sexes was 46 years (range: 2–93 years). Twelve of these patients (6%) were less than 20 years of age. 43% (n = 71) of the epithelial tumors, 85% (n = 12) of the mesenchymal tumors and 50% (n = 11) of the tumors of immune system were seen in patients aged 50 years and less. Malignant non-odontogenic tumors were seen in 194 patients (99%) and malignant odontogenic tumors were seen in 2 patients (1%). 3.1. Tumors of epithelial origin (carcinoma) Tumors of epithelial origin accounted for 7% (160 of 2390) of the total biopsies done during this period. The mean age of these patients was 47 years with a range of 14–93 years. Most of the patients were aged 40 years and above (69%). Palate (n = 39) and cheek (n = 38) were the most common sites of occurrence. The peak age of incidence was seen in the sixth and seventh decade of life. There were 91 males and 69 females at a ratio of 1.31:1 (Tables 1 and 2). Among the epithelial tumors, SCC (50.6%) was the most common neoplasm, followed by mucoepidermoid carcinoma (15%) and adenoid cystic carcinoma (8.7%). About 3.4% of the all the biopsied lesions and 41% of all the primary malignant tumors seen during this period was found to be SCC. Majority of the SCC (85%) were seen in patients of 40 years and above and of them, 62% were males. The tongue (23%) and cheek (21%) were the most commonly involved regions for SCC. Two female patients with malignant ameloblastoma were seen in mandibular posterior region. The incidence of SCC was found to be 2.12 for men and 1.25 for women, with a male to female ratio of 1.61:1. About 85% of the SCC studied during this period occurred in patients aged 40 years and above. By calculating the odds ratio, we found that patients aged 40 years and above were 4.06 times more likely to develop SCC than those aged less than 40 years. Well-differentiated SCC (59%) was found to be the commonest histological subtype of SCC (Tables 3 and 4). 3.2. Tumors of immune system Tumors of immune system accounted for 1% (22 of 2390) of the total biopsies done in this period. Lymphoma constituted 8% (16 of 196) of the total primary malignant tumors and 72% (16 of 22) of the malignant tumors of immune system. Non-Hodgkins lymphoma (36%) was the most common tumor, followed by Burkitt’s
Table 1 Tumors of epithelial origin according to age and sex. Epithelial tumors
Age group in years 0–10
11–20
Squamous cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Adenocarcinoma Malignant pleomorphic adenoma Verrucous carcinoma Adeno squamous cell carcinoma Polymorphic low grade adenocarcinoma Malignant ameloblastoma Nasopharyngeal carcinoma Papillary cystic adenocarcinoma Acinic adenoid carcinoma Salivary duct carcinoma Spindle cell carcinoma
0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 2 0 0 0 0 0 0 0 0 0 0 0 0
Total
0
2
Sex
21–30
31–40
41–50
51–60
61–70
6 6 2 0 2 0 2 0 0 0 0 2 0 0
6 10 4 0 2 0 0 2 1 0 2 0 0 0
14 0 2 0 2 1 2 0 1 0 0 0 0 0
22 4 2 0 2 4 0 2 0 2 0 0 0 0
21 2 4 4 0 0 0 0 0 0 0 0 2 1
20
27
22
38
34
71–80
>81
Male
Female
6 0 0 4 0 1 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0 0 0 0 0 0
51 12 4 6 4 6 0 2 0 2 1 1 1 1
30 12 10 2 4 0 4 2 2 0 1 1 1 0
Total 81 24 14 8 8 6 4 4 2 2 2 2 2 1
11
6
91
69
160
(%) 50.6 15 8.7 5 5 3.7 2.5 2.5 1.2 1.2 1.2 1.2 1.2 0.6 100
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
334 Table 2 Tumors of epithelial origin according to site. Histological type
Max
Mand
FOM
Palate
Tongue
RMR
Cheek
Parotid
SMG
MS
Upper lip
Lower lip
Total (%)
Squamous cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Adenocarcinoma Malignant pleomorphic adenoma Verrucous carcinoma Adeno squamous cell carcinoma Polymorphic low grade adenocarcinoma Malignant ameloblastoma Nasopharyngeal carcinoma Papillary cystic adenocarcinoma Acinic adenoid carcinoma Salivary duct carcinoma Spindle cell carcinoma
10 2 4 2 2 0 0 0 0 0 0 0 0 0
14 0 0 0 0 0 0 0 2 0 0 0 0 0
4 0 2 0 0 0 0 0 0 0 0 0 0 0
2 12 2 4 4 1 2 2 0 0 0 0 2 0
19 0 0 0 0 0 0 0 0 0 0 0 0 1
2 0 0 2 0 0 0 0 0 0 0 0 0 0
17 6 2 0 0 3 2 0 0 0 2 0 0 0
0 0 0 0 0 0 0 0 0 0 0 2 0 0
0 2 4 0 0 0 0 0 0 0 0 0 0 0
2 2 0 0 0 0 0 0 0 2 0 0 0 0
2 0 0 0 2 1 0 2 0 0 0 0 0 0
9 0 0 0 0 1 0 0 0 0 0 0 0 0
81 24 14 8 8 6 4 4 2 2 2 2 2 1
Total
20
16
6
31
20
4
32
2
6
6
7
10
160
Max: maxilla; Mand: mandible; FOM: floor of mouth; RMR: retromolar region; SMG: submandibular gland; and MS: maxillary sinus.
Table 3 Age adjusted incidence rates (100,000) of squamous cell carcinoma in the eastern part of Libya between 1991 and 2007. Age group (years)
Male
Female
Total
Number
Incidence
Number
Incidence
Number
Incidence
0–30 31–40 41–50 51–60 61–70 71–80 >81
5 5 10 7 16 3 5
0.20 0.20 0.41 0.29 0.66 0.12 0.20
1 1 4 15 5 3 1
0.04 0.04 0.16 0.62 0.20 0.12 0.04
6 6 14 22 21 6 6
0.25 0.25 0.58 0.91 0.87 0.25 0.25
Total
51
2.12
30
1.25
81
3.375
Table 4 Distribution of histologic subtype of squamous cell carcinoma by ICD-O codes. Anatomic site
ICD-O codes
Tongue Cheek mucosa Mandibular gingiva Maxillary gingiva Lower lip Floor of mouth Hard palate Upper lip
CO2.9 CO6.0 CO3.1 CO3.0 CO0.1 CO4.9 CO5.0 CO0.0
Well differentiated (59%) Male
Total
Female
Moderately (30%) Total
Male
Female
Total
12 14 3 6 8 0 1 2
2 2 2 2 1 2 0 0
4 0 5 2 0 1 2 0
6 2 1 4 1 3 2 0
1 0 1 2 0 0 1 0
0 1 2 0 0 1 0 0
1 1 2 0 1 1 0
19 17 14 12 9 4 4 2
31
17
48
13
11
24
6
3
9
81
Tumors of mesenchymal origin accounted for 0.6% (14 of 2390) of the total biopsies done in this period. The age of the patients ranged from 5 to 65 years and the peak incidence was in the fourth decade of life. The male to female ratio was 2.5:1 and 85% were below 50 years of age. Hemangioendothelioma (43%) was the most common tumor, followed by rhabdomyosarcoma (21%) and fibrosarcoma (14%).
Total
Total (%)
5 3 7 2 4 0 0 0
3.3. Tumors of mesenchymal origin (sarcoma)
Female
Poorly differentiated (11%)
7 11 4 4 4 0 1 2
(18%) and Hodgkin’s lymphoma (18%). Eight cases of NonHodgkins lymphoma were seen, all occurring in patients above 59 years and majority of them involved the submandibular lymph nodes. There were four cases of Burkitt’s lymphoma, two in the mandible and two in the maxilla and all occurring in patients in their first decade.
Male
differentiated
(24) (22) (18) (14) (11) (5) (5) (2)
4. Discussion While abundant data are available on the incidence of malignant tumors of orofacial region from the Western countries, there is little information on the incidence of primary tumors from the Arab countries. We found no population based studies on primary orofacial tumors among the Arab population in the literature. Also among the studies based on ethnic variation, there is a scarcity in the literature on malignant tumors among the Arab population, except few articles from Jordan, Kuwait and Saudi Arabia [14–16]. We believe that this is the first report on the status of orofacial primary malignant tumors in general and the incidence of oral cancer in particular, among the Libyan population. Reports suggest there is a steady increase in the incidence rates of oral malignancies in countries like Slovakia [5], Scotland [6], Nova Scotia (Canada) [7], USA [17], UK [18] and India [19],
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especially among males aged 53 years and above. In a recent study from Libya, El Mistiri et al. [20] found the world age-standardized incidence rate of cancer for all sites combined to be 118 per 100,000 for men and 95 per 100,000 for women and thus confirmed that cancer incidence is much lower than in western countries. In our study, about 50% of the total patients with oral malignant tumors were seen in those who were above 50 years and majority of them were males. Malignant odontogenic tumors constituted for only 1% (n = 2) of all the primary malignant tumors in this study, which is less than those reported from China and Canada [21,22]. Malignant tumors of orofacial region constituted about 14% of all biopsies done during this period of 17 years, which is relatively less than the reports from Zimbabwe (25%) [11], East Java-Indonesia (45.3%) [23] and Nigeria (18%) [24]. Malignant odontogenic tumors constituted for only 1% (n = 2) of all the primary malignant tumors in our study. Epithelial malignant tumors constituted 82% of all malignant neoplasms seen during this period. This is in agreement with most of the previous published reports [10–12,24–26]. SCC was the most common malignancy in the orofacial region in our study, which is consistent with the findings of most of the earlier reports [10– 12,14,24,26,27]. SCC accounted for 41% of all orofacial malignancies. This percentage seems to be the least among the earlier reports from countries like Jordon (66%) [14], Kuwait (56%) [15], Nigeria (63%) [24], USA (83%) [25], Iran (87%) [28], and Zimbabwe (73%) [29]. The most common sites of SCC in our study were found to be the tongue (23%) and cheek (21%). Some studies have shown relatively high incidences of SCC in areas like tongue and mandibular gingiva [14,16,18,23]. There are two major factors that may explain why this region is at high risk: first, any carcinogen would mix with saliva, pool in the bottom of the mouth, and constantly bathe these sites; secondly, these regions of the mouth are covered by a thinner, nonkeratinized mucosa, which provides less protection against carcinogens [8]. Another explanation for the high involvement of these sites was explained by the advanced state of the lesions at the time of presentation leading to difficulty in accurately determining the exact site of origin [11]. However, tongue was the least involved site in the studies by Rawashdeh and Matalka [14] and Ajayi et al. [24]. Many investigators have shown a causal association between oral malignancy and the chewing habits like alshammah and alqat in southern Saudi Arabia and toombak in Sudan and betel quid in India and South East Asia [16,25,28]. The negative health effects of pipe, cigar, and water pipe smoking as well as other forms of tobacco use such as chewing tobacco and moist snuff deposited between cheek and gum are on par or above that of cigarette smoking [29]. In the absence of a clear evidence of chewable tobacco practice in Libya, the reason for frequent involvement of cheek remains unclear and requires detailed investigation. Palate (2%) and maxillary sinus (2%) were the least involved sites for SCC in the present study, which is similar to the findings in Canada [7], UK [18] and USA [30], and contradicting to those from India [19], Nigeria [24], and Zimbabwe [29]. Although, reverse smoking had been implicated in India, the existence of such practice had not been well established in other countries. The huge variation in the incidence of SCC across the globe could be possibly explained by the prevalence of different major risk factors, alcohol and tobacco, geographic variation, genetic and environmental factors [3,25,32]. Epidemiological studies show that the risk of developing oral cancer is five to nine times greater for smokers than for nonsmokers, and this risk may increase to as much as 17 times greater for extremely heavy smokers [31]. Alcohol and tobacco consumption are independent risk factors and in combination they interact synergistically to further amplify the risk of oral malignancy.
335
Most of the Libyan populations are Muslims and their religion prohibits them from consuming alcohol. Cigarette smoking is replacing the traditional water pipe smoking, which is locally known as ‘‘hookah’’ or ‘‘shisha’’, is still used in cafes and restaurants. Smoking is common among Libyan men. Although the prevalence of smokers had not been studied extensively, it is reasonable to implicate smoking as a critical risk factor for oral malignancy among middle aged men in this country. About 37% of the patients with SCC were women, which is another interesting finding in this study. Several reports have indicated that dental sepsis, poor oral hygiene and chronic irritation from teeth, restoration or dentures may contribute in initiation or exacerbation of oral malignancy [19,32]. Also obesity and a diet rich in fat, butter, eggs and starchy foods were found to be positively associated with risk of oral malignancy [32]. Several trials worldwide on micronutrients and chemoprevention showed that a diet rich in Vitamins A, C, E and beta-carotene supplements have been associated with a reduced risk of oral cancer [3,8,32]. Iron deficiency is known to affect the integrity and function of the oral mucosa and thus may render it more susceptible to the effects of carcinogens and has been associated with malignancy of the oral cavity [3,14]. Since there is no concrete knowledge on the dietary habits, oral hygiene status, prevalence of anemia and iron deficiency among Libyan women, it would be premature to vindicate any one of these factors in the pathogenesis of oral malignancy. Other risk factors for oral malignancy include oncogenic viruses, exposure to radiation, immune status, socioeconomic status and possible genetic characteristics [1,4]. For example, human papilloma virus (type 16) had been recently been associated with a 2.2 fold increase in the risk of SCC [27]. Similar to the findings of earlier reports, well-differentiated SCC (59%) were the common histologic subtype seen in our study. Considering the site predilections, the tongue and cheek mucosa had more cases of well-differentiated SCC, while the maxillary and mandibular gingiva were associated with moderately differentiated and poorly differentiated subtypes. Although the well-differentiated SCC is believed to have a good prognosis, other indicators like invasive pattern, tumor margins and lymph node involvement play a crucial role in determining the exact prognostic significance. The incidence of malignant tumors of lip shows huge geographical variation with high rates being reported from Australia, Canada and Europe, and extremely low rates in China, Japan and Singapore [33]. This study reports malignant tumors among the Libyans with age-standardized incidence rates per 100,000 (World Standard Population) of 1.35, which is fairly more than the Europeans and Asians (0.2–1.1), but far less than from Australia and Canada (12–14.8) [33]. Studies have shown that higher incidence of lip malignancies occurs among outdoor workers, rural population and fair skinned individuals and who have chronic exposure to solar radiation (ultra-violet B) [4,8,29]. Libya is located in Northern Africa, bordering the Mediterranean Sea between Egypt and Tunisia, geographically between 32– 53 North and 13–10 East. It has a pleasant Mediterranean climate along the coast and a dry, extreme desert in the southern part. Libyans are Arabs who are classified as Caucasoid and considered fair skinned having type III and type IV skin, which is characterized by mild to moderate risk of skin cancer [14,15,33]. Langerhans cells histiocytosis (LCH) is a true proliferation of cells of the immune system owing to its histogenesis from the ubiquitous dendritic antigen processing and presenting cells, termed Langerhans cells. The term ‘‘eosinophilic granuloma’’ denotes the common low grade biology of most LCH lesions and may be either unifocal or multifocal [34]. These features prompted us to include our five cases of LCH as a tumor of immune system, as done by Marx and Stern [34].
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336
In our study lymphomas constituted 8% of the all orofacial malignancies, which is higher than those reported from the Jordon and some African countries [14,15,26]. Hodgkin’s lymphoma accounted for 25% of all lymphomas seen in this series and all the cases were seen in the submandibular lymph nodes. Non-Hodgkin’s lymphoma was seen in 75% of all lymphomas, of which 25% being Burkitt’s lymphoma. Burkitt’s lymphoma is a common malignancy in childhood in East and Central Africa, which is strongly associated with Epstein-Barr virus [11,24]. All our cases of BL were seen in children in their first decade, with an age range of 2–4 years. Burkitt’s lymphoma constituted only 2% of all orofacial malignant tumors in this study, which is less than those reported by Chidzonga (5%) [11] and Ajayi et al. (7%) [24]. Sarcomas of the orofacial region accounted for about 7% of all malignant tumors in this population. As seen in most of the studies, sarcomas were less common than carcinomas and were seen in younger people than the carcinomas [24,26]. Hemangioendothelioma constituted for 3% of all orofacial malignant tumors and 43% of all cases of sarcomas. It is a low grade malignant neoplasm of mesenchymal origin which is angiomatous in nature and derived from the endothelial cells [22]. Malignant minor salivary gland tumors accounted for 34% of all the primary malignant tumors of orofacial region (66 out of 196) and 92% of all the tumors of salivary glands (66 out of 72). Palate (38%) was the most frequently involved site and mucoepidermoid carcinoma (33%) was the most common malignant tumor of the minor salivary glands. This is consistent with most of the findings of earlier reports [23,35]. Retrospective studies like this have their limitations and possible bias. Patients falling in any one of the following categories could be missed in this study: people seeking medical treatment in neighboring countries, lesions that were not sent for histopathological examination after excision, undiagnosed patients with malignancy, and patients treated in the private hospitals. Libya has got one of the highest per capita GDPs in Africa (5.4%) and a literacy rate of over 80%. The life expectancy at birth is about 76 years, which is higher than any country in Africa [13]. In addition to the primary care, most of the specialized treatment is offered free for the people in Libya by the Ministry of health. Considering all these factors, we believe that the incidence rates found in our study are unlikely to be affected by above mentioned conditions. In conclusion, the incidence of oral malignancy is impressively low with respect to other countries in Africa and some European countries. This represents a great potential for etiological studies on the role of behavioral, dietary, environmental and genetic risk factors. Accordingly, preventive measures and awareness campaigns should be arranged by the international agencies and government authorities. Conflict of interest statement None declared. References [1] Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, et al., eds. SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute, 2008 . http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site. [2] Parkin DM, Pisani P, Ferlay J, Powell J. Estimate of worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–41. [3] La Vecchia C, Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol 1997;33(5):302–12.
[4] Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of mouth cancer: a review of global incidence. Oral Dis 2000;6:65–74. [5] Plesko I, Macfarlane GJ, Evstifeeva TV, Obsitnikova A, Kramarova E. Oral and pharyngeal cancer incidence in Slovakia 1968–1989. Int J Cancer 1994;56(4): 481–6. [6] Robinson KL, Macfarlane GJ. Oropharyngeal cancer incidence and mortality in Scotland: are rates still increasing? Oral Oncol 2003;39:31–6. [7] Howell RE, Wright BA, Dewar R. Trends in the incidence of oral cancer in Nova Scotia from 1983 to 1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:205–12. [8] Johnson NW. Orofacial neoplasms: global epidemiology, risk factors and recommendations for research. Int Dent J 1991;41:365–75. [9] Arotiba GT, Ladeinde AL, Oyeneyin JO, Nwawolo CC, Banjo AA, Ajayi OF. Malignant orofacial neoplasms in Lagos, Nigeria. East Afr Med J 2006;83(3): 62–8. [10] Arotiba JT, Obiechina AE, Fasola OA, Fawole OI, Ajagbe HA. Oral squamous cell carcinoma: a review of 246 Nigerian cases. Afr J Med Sci 1999;28(3–4):141–4. [11] Chidzonga MM. Oral malignant neoplasia: a survey of 428 cases in two Zimbabwean hospitals. Oral Oncol 2006;42:177–83. [12] Jaber MA. Intraoral minor salivary gland tumors: a review of 75 cases in a Libyan population. Int J Oral Maxillofac Surg 2006;35:150–4. [13] http://www.prb.org/publications/Datasheets/2006/2006WorldPopulationDataSheet.aspx. [14] Rawashdeh MA, Matalka I. Malignant oral tumors in Jordanians 1991–2001. Int J Oral Maxillofac Surg 2004;33:183–8. [15] Morris RE, Al Mahmeed VE, Gjogov AN, Al Jazaff HG, Al Rashi B. The epidemiology of lip, oral cavity and pharyngeal cancers in Kuwait 1975–1988. J Oral Maxillofac Surg 2000;38:316–9. [16] Ibrahim EM, Satti MB, Al Idrissi HY, Higazi MM, Magbool GM, Al Quorain A. Oral cancer in Saudi Arabia: the role of alqat and alshammah. Cancer Detect Prev 1986;9(3–4):215–8. [17] Shiboski C, Shiboski S, Silverman Jr S. Trends in oral cancer in the United States, 1973–1996. Community Dent Oral Epidemiol 2000;28:249–56. [18] Hindle I, Nally F. Oral cancer: a comparative study between 1962–1967 and 1980–1984 in England and Wales. Br Dent J 1991;170:15–20. [19] Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nandakumar A, et al. Oral cancer in southern India: the influence of smoking, drinking, paan chewing and oral hygiene. Int J Cancer 2002;98:440–5. [20] El Mistiri M, Verdecchia A, Rashid I, El Sahli N, El Mangush M, Federico M. Cancer incidence in eastern Libya: the first report from the Benghazi Cancer Registry, 2003. Int J Cancer 2007;15:392–7. [21] Lu Y, Xuan M, Takata T, Wang C, He Z, Zhou Z, et al. Odontogenic tumors. A demographic study of 759 cases in a Chinese population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(6):707–14. [22] Daley TM, Wysochi GP, Pringle GA. Relative incidence of odontogenic tumors and oral jaw cysts in a Canadian population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1994;77:276–80. [23] Budhy TI, Soenarto, Yacoob HB, Ngeow WC. Changing incidence of oral and maxillofacial tumours in East Java, Indonesia, 1987–1992. Part 2: Malignant tumours. Br J Oral Maxillofac Surg 2001;39:460–4. [24] Ajayi OF, Adeyemo WL, Ladeinde AL, Ogunlewe MO, Effiom OA, Omitola OG, et al. Primary malignant neoplasms of orofacial origin; a retrospective review of 256 cases in a Nigerian tertiary hospital. Int J Oral Maxillofac Surg 2007;36:403–8. [25] Canto MT, Devesa SS. Oral cavity and pharyngeal cancer incidence rates in the United States, 1975–1998. Oral Oncol 2002;38:610–7. [26] Otoh EC, Johnson NW, Danfillo IS, Adeleke OA, Olasoji HA. Primary head and neck cancers in North-eastern Nigeria. West Afr J Med 2004;23:305–13. [27] Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. New Engl J Med 2001;344(15):1125–31. [28] Sargeran K, Murtumaa H, Safavi SMR, Vehkalahti M, Teronen O. Malignant oral tumors in Iran: ten year analysis on patient and tumor characteristics of 1042 patients in Tehran. J Craniofac Surg 2006;17:1230–3. [29] Burns DM. Nicotine addiction. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. 15th ed., Harrisons principles of internal medicine, vol. 2, 15th ed. Mc Graw Hill Company; 2001: 2574–7. [30] Krutchkoff DJ, Chen J, Eisenberg E, Katz RV. Oral cancer: a survey of 566 cases from the University of Connecticut Oral Pathology Biology Service 1975–1986. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1990;70:192–8. [31] Jovanovic A, Schulten EA, Kostense PJ, Snow GB, van der Waal I. Tobacco and alcohol related to the anatomical site of oral squamous cell carcinoma. J Oral Pathol Med 1993;22(10):459–62. [32] Zain RB. Cultural and dietary risk factors of oral cancer and precancer—a brief overview. Oral Cancer 2001;37:205–10. [33] Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of lip cancer: a review of global incidence. Oral Dis 1999;5:185–95. [34] Marx R, Stern D. Oral and maxillofacial pathology. A rationale for diagnosis and treatment. Quintessence Publishing Co., Inc.; 2003. p. 865–69, 870–75. [35] Wang D, Li Y, Huawei H, Liu L, Wu L, He Z. Intraoral minor salivary gland tumors in a Chinese population: a retrospective study on 737 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104(1):94–100.
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Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Primary malignant tumors of orofacial region at Benghazi, Libya: A 17 years review Krishnaraj Subhashraj a,*, Maraai Orafi a, K.V. Nair a, Rafa El-Gehani a, Mohammed Elarbi b a b
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Al-Arab Medical Science University, Benghazi, Libya Department of Oral and Maxillofacial Surgery, Al-Fatah University, Tripoli, Libya
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 19 October 2009
The aim of this study was to systematically analyze the clinical presentations of orofacial malignant tumors in a Libyan population over a period of 17 years and compare the results with the reports from other countries. During the study period, tumors of epithelial origin were found in 160 patients (82%), followed by tumors of immune system, 22 (11%) and tumors of mesenchymal origin, 14 (7%). Of the total malignant tumors, 115 were men and 81 were women and the male to female ratio was 1.41:1. Malignant non-odontogenic tumors were seen in 194 patients (99%) and malignant odontogenic tumors were seen in 2 patients (1%). Among the epithelial tumors, squamous cell carcinoma (50.6%) was the most common neoplasm, followed by mucoepidermoid carcinoma (15%) and adenoid cystic carcinoma (8.7%). The incidence of oral malignancy is impressively low with respect to the corresponding levels in other countries in Africa and some European countries. ß 2009 Elsevier Ltd. All rights reserved.
Keywords: Malignant tumors Squamous cell carcinoma Orofacial Incidence Tongue Floor of the mouth
1. Introduction Cancers of the mouth and oropharynx are the sixth most common malignancy globally [1]. Epidemiology shows that head and neck cancers constitute between 5% and 50% of all cancers, while the orofacial region is found to be the commonest site [2]. It poses a serious health problem for the patient, a challenge for the surgeon and a burden for the society. The incidence of oral cancer shows huge geographic variation, from as low as 1–2% of all malignant tumors in Japan, to around 50% in India [2]. Although the incidence of oral cancer is relatively low (2–6%) in Western countries, there has been a recent dramatic increase in the mortality rate in some European countries [3–8]. There have been only few reports published on malignant neoplasms of the orofacial region from the African continent [9– 11]. Till date, no epidemiological studies on malignant tumors of the orofacial region have been done in Libya, except one study on intraoral minor salivary gland tumors [12]. Knowledge on the incidence of malignant tumors of orofacial region is vital for better understanding of the biology of the disease and for proper diagnosis, treatment and prevention. The purpose of this study was to systematically analyze the clinical presentations of orofacial malignant tumors in a Libyan
* Corresponding author. Tel.: +218 913681026. E-mail addresses: [email protected], [email protected] (K. Subhashraj). 1877-7821/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.canep.2009.10.009
population seen over a period of 17 years and compare the results with the reports from other countries. This paper could be of good clinical importance in assessing all the risk factors in addition to the genetic and environmental influences, because of the fact that although Libya is geographically in the continent of Africa, it has an ethnic population of Arabs. 2. Materials and methods This retrospective study was carried out at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Garyounis University, Benghazi, Libyan Arab Jamahiriya. Libya is located in Northern Africa, bordering the Mediterranean Sea, between Egypt and Tunisia. While Tripoli is the capital of Libya, Benghazi is the second largest city in the country. The faculty of Dentistry at Benghazi was established in 1977 and since then it serves as the only referral center for maxillofacial trauma and pathology for the population of eastern Libya. Libya has an estimated population of about 6.03 million, and the life expectancy at birth of 76.88 years. About 97% of the populations are Arab and Berber and most of them are Muslims [13]. The medical reports and biopsy files of patients who underwent biopsy in the maxillofacial region for various reasons between January 1991 and December 2007 were retrieved from the Department of Oral and Maxillofacial Pathology. For all the cases, the clinical records were re-examined by the authors and the histological sections were also re-confirmed by two senior staffs from the Department of Pathology. The following were the
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
exclusion criteria: incomplete clinical data, reports with doubtful or controversial diagnosis, those with metastatic tumors and reports of non-Libyan nationals. The primary malignant tumors were broadly classified into three categories: tumors of epithelial origin, tumors of mesenchymal origin and tumors of the immune system. Information about age, sex, tumor location and histological type were obtained from each record. Age adjusted standardized incidence rates of squamous cell carcinoma (SCC) were calculated by using the direct method and the world standard population expressed per 100,000 persons using the standard 10-year age divisions. Thus the incidence rates are compared with data from other countries. The population of eastern Libya in 2005 was estimated to be 2.1 million, which is about slightly more than one third of total population of Libya. The patients seen here are thus fairly representative of the Libyan population. The purpose of this study was intended to provide information to health professionals and health authorities, which could be used for community education, diagnosis, early treatment and research. Data was analyzed using the SPSS for Microsoft Windows (version 13; SPSS, Chicago, Ill) statistical software package. Descriptive statistics and test of significance were used as appropriate. The critical level of significance was set at P < 0.05. 3. Results During a period of 17 years, we reviewed the files of 2390 patients who underwent biopsy for various reasons in the orofacial region. Of the total 2390 patients who underwent biopsy in maxillofacial region at our center, 906 (38%) patients had inflammatory and reactive diseases, 432 (18%) had developmental and inflammatory cysts, 405 (16%) had benign odontogenic and non-odontogenic tumors, 196 (8%) had primary malignant tumors, 138 (6%) had premalignant epithelial lesions of mucosa and skin, 89 (4%) had immune based diseases, 7 (<1%) had metastatic tumors and 217 (9%) were grouped as miscellaneous (developmental disturbances, gingival hyperplasia, non-neoplastic salivary gland diseases, etc.). The malignant tumors of orofacial region were broadly classified into three groups: tumors of epithelial region, tumors of mesenchymal region and tumors of the immune system. The relative frequency of different types of primary malignant tumors was classified according to the histological classification, age, gender and location. During the study period, tumors of epithelial origin were found in 160 patients (82%), followed by tumors of immune system, 22
333
(11%) and tumors of mesenchymal origin, 14 (7%). Of the total malignant tumors, 115 were men and 81 were women and a male to female ratio of 1.41:1. The mean age of the patients in both the sexes was 46 years (range: 2–93 years). Twelve of these patients (6%) were less than 20 years of age. 43% (n = 71) of the epithelial tumors, 85% (n = 12) of the mesenchymal tumors and 50% (n = 11) of the tumors of immune system were seen in patients aged 50 years and less. Malignant non-odontogenic tumors were seen in 194 patients (99%) and malignant odontogenic tumors were seen in 2 patients (1%). 3.1. Tumors of epithelial origin (carcinoma) Tumors of epithelial origin accounted for 7% (160 of 2390) of the total biopsies done during this period. The mean age of these patients was 47 years with a range of 14–93 years. Most of the patients were aged 40 years and above (69%). Palate (n = 39) and cheek (n = 38) were the most common sites of occurrence. The peak age of incidence was seen in the sixth and seventh decade of life. There were 91 males and 69 females at a ratio of 1.31:1 (Tables 1 and 2). Among the epithelial tumors, SCC (50.6%) was the most common neoplasm, followed by mucoepidermoid carcinoma (15%) and adenoid cystic carcinoma (8.7%). About 3.4% of the all the biopsied lesions and 41% of all the primary malignant tumors seen during this period was found to be SCC. Majority of the SCC (85%) were seen in patients of 40 years and above and of them, 62% were males. The tongue (23%) and cheek (21%) were the most commonly involved regions for SCC. Two female patients with malignant ameloblastoma were seen in mandibular posterior region. The incidence of SCC was found to be 2.12 for men and 1.25 for women, with a male to female ratio of 1.61:1. About 85% of the SCC studied during this period occurred in patients aged 40 years and above. By calculating the odds ratio, we found that patients aged 40 years and above were 4.06 times more likely to develop SCC than those aged less than 40 years. Well-differentiated SCC (59%) was found to be the commonest histological subtype of SCC (Tables 3 and 4). 3.2. Tumors of immune system Tumors of immune system accounted for 1% (22 of 2390) of the total biopsies done in this period. Lymphoma constituted 8% (16 of 196) of the total primary malignant tumors and 72% (16 of 22) of the malignant tumors of immune system. Non-Hodgkins lymphoma (36%) was the most common tumor, followed by Burkitt’s
Table 1 Tumors of epithelial origin according to age and sex. Epithelial tumors
Age group in years 0–10
11–20
Squamous cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Adenocarcinoma Malignant pleomorphic adenoma Verrucous carcinoma Adeno squamous cell carcinoma Polymorphic low grade adenocarcinoma Malignant ameloblastoma Nasopharyngeal carcinoma Papillary cystic adenocarcinoma Acinic adenoid carcinoma Salivary duct carcinoma Spindle cell carcinoma
0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 2 0 0 0 0 0 0 0 0 0 0 0 0
Total
0
2
Sex
21–30
31–40
41–50
51–60
61–70
6 6 2 0 2 0 2 0 0 0 0 2 0 0
6 10 4 0 2 0 0 2 1 0 2 0 0 0
14 0 2 0 2 1 2 0 1 0 0 0 0 0
22 4 2 0 2 4 0 2 0 2 0 0 0 0
21 2 4 4 0 0 0 0 0 0 0 0 2 1
20
27
22
38
34
71–80
>81
Male
Female
6 0 0 4 0 1 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0 0 0 0 0 0
51 12 4 6 4 6 0 2 0 2 1 1 1 1
30 12 10 2 4 0 4 2 2 0 1 1 1 0
Total 81 24 14 8 8 6 4 4 2 2 2 2 2 1
11
6
91
69
160
(%) 50.6 15 8.7 5 5 3.7 2.5 2.5 1.2 1.2 1.2 1.2 1.2 0.6 100
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
334 Table 2 Tumors of epithelial origin according to site. Histological type
Max
Mand
FOM
Palate
Tongue
RMR
Cheek
Parotid
SMG
MS
Upper lip
Lower lip
Total (%)
Squamous cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Adenocarcinoma Malignant pleomorphic adenoma Verrucous carcinoma Adeno squamous cell carcinoma Polymorphic low grade adenocarcinoma Malignant ameloblastoma Nasopharyngeal carcinoma Papillary cystic adenocarcinoma Acinic adenoid carcinoma Salivary duct carcinoma Spindle cell carcinoma
10 2 4 2 2 0 0 0 0 0 0 0 0 0
14 0 0 0 0 0 0 0 2 0 0 0 0 0
4 0 2 0 0 0 0 0 0 0 0 0 0 0
2 12 2 4 4 1 2 2 0 0 0 0 2 0
19 0 0 0 0 0 0 0 0 0 0 0 0 1
2 0 0 2 0 0 0 0 0 0 0 0 0 0
17 6 2 0 0 3 2 0 0 0 2 0 0 0
0 0 0 0 0 0 0 0 0 0 0 2 0 0
0 2 4 0 0 0 0 0 0 0 0 0 0 0
2 2 0 0 0 0 0 0 0 2 0 0 0 0
2 0 0 0 2 1 0 2 0 0 0 0 0 0
9 0 0 0 0 1 0 0 0 0 0 0 0 0
81 24 14 8 8 6 4 4 2 2 2 2 2 1
Total
20
16
6
31
20
4
32
2
6
6
7
10
160
Max: maxilla; Mand: mandible; FOM: floor of mouth; RMR: retromolar region; SMG: submandibular gland; and MS: maxillary sinus.
Table 3 Age adjusted incidence rates (100,000) of squamous cell carcinoma in the eastern part of Libya between 1991 and 2007. Age group (years)
Male
Female
Total
Number
Incidence
Number
Incidence
Number
Incidence
0–30 31–40 41–50 51–60 61–70 71–80 >81
5 5 10 7 16 3 5
0.20 0.20 0.41 0.29 0.66 0.12 0.20
1 1 4 15 5 3 1
0.04 0.04 0.16 0.62 0.20 0.12 0.04
6 6 14 22 21 6 6
0.25 0.25 0.58 0.91 0.87 0.25 0.25
Total
51
2.12
30
1.25
81
3.375
Table 4 Distribution of histologic subtype of squamous cell carcinoma by ICD-O codes. Anatomic site
ICD-O codes
Tongue Cheek mucosa Mandibular gingiva Maxillary gingiva Lower lip Floor of mouth Hard palate Upper lip
CO2.9 CO6.0 CO3.1 CO3.0 CO0.1 CO4.9 CO5.0 CO0.0
Well differentiated (59%) Male
Total
Female
Moderately (30%) Total
Male
Female
Total
12 14 3 6 8 0 1 2
2 2 2 2 1 2 0 0
4 0 5 2 0 1 2 0
6 2 1 4 1 3 2 0
1 0 1 2 0 0 1 0
0 1 2 0 0 1 0 0
1 1 2 0 1 1 0
19 17 14 12 9 4 4 2
31
17
48
13
11
24
6
3
9
81
Tumors of mesenchymal origin accounted for 0.6% (14 of 2390) of the total biopsies done in this period. The age of the patients ranged from 5 to 65 years and the peak incidence was in the fourth decade of life. The male to female ratio was 2.5:1 and 85% were below 50 years of age. Hemangioendothelioma (43%) was the most common tumor, followed by rhabdomyosarcoma (21%) and fibrosarcoma (14%).
Total
Total (%)
5 3 7 2 4 0 0 0
3.3. Tumors of mesenchymal origin (sarcoma)
Female
Poorly differentiated (11%)
7 11 4 4 4 0 1 2
(18%) and Hodgkin’s lymphoma (18%). Eight cases of NonHodgkins lymphoma were seen, all occurring in patients above 59 years and majority of them involved the submandibular lymph nodes. There were four cases of Burkitt’s lymphoma, two in the mandible and two in the maxilla and all occurring in patients in their first decade.
Male
differentiated
(24) (22) (18) (14) (11) (5) (5) (2)
4. Discussion While abundant data are available on the incidence of malignant tumors of orofacial region from the Western countries, there is little information on the incidence of primary tumors from the Arab countries. We found no population based studies on primary orofacial tumors among the Arab population in the literature. Also among the studies based on ethnic variation, there is a scarcity in the literature on malignant tumors among the Arab population, except few articles from Jordan, Kuwait and Saudi Arabia [14–16]. We believe that this is the first report on the status of orofacial primary malignant tumors in general and the incidence of oral cancer in particular, among the Libyan population. Reports suggest there is a steady increase in the incidence rates of oral malignancies in countries like Slovakia [5], Scotland [6], Nova Scotia (Canada) [7], USA [17], UK [18] and India [19],
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
especially among males aged 53 years and above. In a recent study from Libya, El Mistiri et al. [20] found the world age-standardized incidence rate of cancer for all sites combined to be 118 per 100,000 for men and 95 per 100,000 for women and thus confirmed that cancer incidence is much lower than in western countries. In our study, about 50% of the total patients with oral malignant tumors were seen in those who were above 50 years and majority of them were males. Malignant odontogenic tumors constituted for only 1% (n = 2) of all the primary malignant tumors in this study, which is less than those reported from China and Canada [21,22]. Malignant tumors of orofacial region constituted about 14% of all biopsies done during this period of 17 years, which is relatively less than the reports from Zimbabwe (25%) [11], East Java-Indonesia (45.3%) [23] and Nigeria (18%) [24]. Malignant odontogenic tumors constituted for only 1% (n = 2) of all the primary malignant tumors in our study. Epithelial malignant tumors constituted 82% of all malignant neoplasms seen during this period. This is in agreement with most of the previous published reports [10–12,24–26]. SCC was the most common malignancy in the orofacial region in our study, which is consistent with the findings of most of the earlier reports [10– 12,14,24,26,27]. SCC accounted for 41% of all orofacial malignancies. This percentage seems to be the least among the earlier reports from countries like Jordon (66%) [14], Kuwait (56%) [15], Nigeria (63%) [24], USA (83%) [25], Iran (87%) [28], and Zimbabwe (73%) [29]. The most common sites of SCC in our study were found to be the tongue (23%) and cheek (21%). Some studies have shown relatively high incidences of SCC in areas like tongue and mandibular gingiva [14,16,18,23]. There are two major factors that may explain why this region is at high risk: first, any carcinogen would mix with saliva, pool in the bottom of the mouth, and constantly bathe these sites; secondly, these regions of the mouth are covered by a thinner, nonkeratinized mucosa, which provides less protection against carcinogens [8]. Another explanation for the high involvement of these sites was explained by the advanced state of the lesions at the time of presentation leading to difficulty in accurately determining the exact site of origin [11]. However, tongue was the least involved site in the studies by Rawashdeh and Matalka [14] and Ajayi et al. [24]. Many investigators have shown a causal association between oral malignancy and the chewing habits like alshammah and alqat in southern Saudi Arabia and toombak in Sudan and betel quid in India and South East Asia [16,25,28]. The negative health effects of pipe, cigar, and water pipe smoking as well as other forms of tobacco use such as chewing tobacco and moist snuff deposited between cheek and gum are on par or above that of cigarette smoking [29]. In the absence of a clear evidence of chewable tobacco practice in Libya, the reason for frequent involvement of cheek remains unclear and requires detailed investigation. Palate (2%) and maxillary sinus (2%) were the least involved sites for SCC in the present study, which is similar to the findings in Canada [7], UK [18] and USA [30], and contradicting to those from India [19], Nigeria [24], and Zimbabwe [29]. Although, reverse smoking had been implicated in India, the existence of such practice had not been well established in other countries. The huge variation in the incidence of SCC across the globe could be possibly explained by the prevalence of different major risk factors, alcohol and tobacco, geographic variation, genetic and environmental factors [3,25,32]. Epidemiological studies show that the risk of developing oral cancer is five to nine times greater for smokers than for nonsmokers, and this risk may increase to as much as 17 times greater for extremely heavy smokers [31]. Alcohol and tobacco consumption are independent risk factors and in combination they interact synergistically to further amplify the risk of oral malignancy.
335
Most of the Libyan populations are Muslims and their religion prohibits them from consuming alcohol. Cigarette smoking is replacing the traditional water pipe smoking, which is locally known as ‘‘hookah’’ or ‘‘shisha’’, is still used in cafes and restaurants. Smoking is common among Libyan men. Although the prevalence of smokers had not been studied extensively, it is reasonable to implicate smoking as a critical risk factor for oral malignancy among middle aged men in this country. About 37% of the patients with SCC were women, which is another interesting finding in this study. Several reports have indicated that dental sepsis, poor oral hygiene and chronic irritation from teeth, restoration or dentures may contribute in initiation or exacerbation of oral malignancy [19,32]. Also obesity and a diet rich in fat, butter, eggs and starchy foods were found to be positively associated with risk of oral malignancy [32]. Several trials worldwide on micronutrients and chemoprevention showed that a diet rich in Vitamins A, C, E and beta-carotene supplements have been associated with a reduced risk of oral cancer [3,8,32]. Iron deficiency is known to affect the integrity and function of the oral mucosa and thus may render it more susceptible to the effects of carcinogens and has been associated with malignancy of the oral cavity [3,14]. Since there is no concrete knowledge on the dietary habits, oral hygiene status, prevalence of anemia and iron deficiency among Libyan women, it would be premature to vindicate any one of these factors in the pathogenesis of oral malignancy. Other risk factors for oral malignancy include oncogenic viruses, exposure to radiation, immune status, socioeconomic status and possible genetic characteristics [1,4]. For example, human papilloma virus (type 16) had been recently been associated with a 2.2 fold increase in the risk of SCC [27]. Similar to the findings of earlier reports, well-differentiated SCC (59%) were the common histologic subtype seen in our study. Considering the site predilections, the tongue and cheek mucosa had more cases of well-differentiated SCC, while the maxillary and mandibular gingiva were associated with moderately differentiated and poorly differentiated subtypes. Although the well-differentiated SCC is believed to have a good prognosis, other indicators like invasive pattern, tumor margins and lymph node involvement play a crucial role in determining the exact prognostic significance. The incidence of malignant tumors of lip shows huge geographical variation with high rates being reported from Australia, Canada and Europe, and extremely low rates in China, Japan and Singapore [33]. This study reports malignant tumors among the Libyans with age-standardized incidence rates per 100,000 (World Standard Population) of 1.35, which is fairly more than the Europeans and Asians (0.2–1.1), but far less than from Australia and Canada (12–14.8) [33]. Studies have shown that higher incidence of lip malignancies occurs among outdoor workers, rural population and fair skinned individuals and who have chronic exposure to solar radiation (ultra-violet B) [4,8,29]. Libya is located in Northern Africa, bordering the Mediterranean Sea between Egypt and Tunisia, geographically between 32– 53 North and 13–10 East. It has a pleasant Mediterranean climate along the coast and a dry, extreme desert in the southern part. Libyans are Arabs who are classified as Caucasoid and considered fair skinned having type III and type IV skin, which is characterized by mild to moderate risk of skin cancer [14,15,33]. Langerhans cells histiocytosis (LCH) is a true proliferation of cells of the immune system owing to its histogenesis from the ubiquitous dendritic antigen processing and presenting cells, termed Langerhans cells. The term ‘‘eosinophilic granuloma’’ denotes the common low grade biology of most LCH lesions and may be either unifocal or multifocal [34]. These features prompted us to include our five cases of LCH as a tumor of immune system, as done by Marx and Stern [34].
K. Subhashraj et al. / Cancer Epidemiology 33 (2009) 332–336
336
In our study lymphomas constituted 8% of the all orofacial malignancies, which is higher than those reported from the Jordon and some African countries [14,15,26]. Hodgkin’s lymphoma accounted for 25% of all lymphomas seen in this series and all the cases were seen in the submandibular lymph nodes. Non-Hodgkin’s lymphoma was seen in 75% of all lymphomas, of which 25% being Burkitt’s lymphoma. Burkitt’s lymphoma is a common malignancy in childhood in East and Central Africa, which is strongly associated with Epstein-Barr virus [11,24]. All our cases of BL were seen in children in their first decade, with an age range of 2–4 years. Burkitt’s lymphoma constituted only 2% of all orofacial malignant tumors in this study, which is less than those reported by Chidzonga (5%) [11] and Ajayi et al. (7%) [24]. Sarcomas of the orofacial region accounted for about 7% of all malignant tumors in this population. As seen in most of the studies, sarcomas were less common than carcinomas and were seen in younger people than the carcinomas [24,26]. Hemangioendothelioma constituted for 3% of all orofacial malignant tumors and 43% of all cases of sarcomas. It is a low grade malignant neoplasm of mesenchymal origin which is angiomatous in nature and derived from the endothelial cells [22]. Malignant minor salivary gland tumors accounted for 34% of all the primary malignant tumors of orofacial region (66 out of 196) and 92% of all the tumors of salivary glands (66 out of 72). Palate (38%) was the most frequently involved site and mucoepidermoid carcinoma (33%) was the most common malignant tumor of the minor salivary glands. This is consistent with most of the findings of earlier reports [23,35]. Retrospective studies like this have their limitations and possible bias. Patients falling in any one of the following categories could be missed in this study: people seeking medical treatment in neighboring countries, lesions that were not sent for histopathological examination after excision, undiagnosed patients with malignancy, and patients treated in the private hospitals. Libya has got one of the highest per capita GDPs in Africa (5.4%) and a literacy rate of over 80%. The life expectancy at birth is about 76 years, which is higher than any country in Africa [13]. In addition to the primary care, most of the specialized treatment is offered free for the people in Libya by the Ministry of health. Considering all these factors, we believe that the incidence rates found in our study are unlikely to be affected by above mentioned conditions. In conclusion, the incidence of oral malignancy is impressively low with respect to other countries in Africa and some European countries. This represents a great potential for etiological studies on the role of behavioral, dietary, environmental and genetic risk factors. Accordingly, preventive measures and awareness campaigns should be arranged by the international agencies and government authorities. Conflict of interest statement None declared. References [1] Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, et al., eds. SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute, 2008 . http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site. [2] Parkin DM, Pisani P, Ferlay J, Powell J. Estimate of worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–41. [3] La Vecchia C, Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol 1997;33(5):302–12.
[4] Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of mouth cancer: a review of global incidence. Oral Dis 2000;6:65–74. [5] Plesko I, Macfarlane GJ, Evstifeeva TV, Obsitnikova A, Kramarova E. Oral and pharyngeal cancer incidence in Slovakia 1968–1989. Int J Cancer 1994;56(4): 481–6. [6] Robinson KL, Macfarlane GJ. Oropharyngeal cancer incidence and mortality in Scotland: are rates still increasing? Oral Oncol 2003;39:31–6. [7] Howell RE, Wright BA, Dewar R. Trends in the incidence of oral cancer in Nova Scotia from 1983 to 1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:205–12. [8] Johnson NW. Orofacial neoplasms: global epidemiology, risk factors and recommendations for research. Int Dent J 1991;41:365–75. [9] Arotiba GT, Ladeinde AL, Oyeneyin JO, Nwawolo CC, Banjo AA, Ajayi OF. Malignant orofacial neoplasms in Lagos, Nigeria. East Afr Med J 2006;83(3): 62–8. [10] Arotiba JT, Obiechina AE, Fasola OA, Fawole OI, Ajagbe HA. Oral squamous cell carcinoma: a review of 246 Nigerian cases. Afr J Med Sci 1999;28(3–4):141–4. [11] Chidzonga MM. Oral malignant neoplasia: a survey of 428 cases in two Zimbabwean hospitals. Oral Oncol 2006;42:177–83. [12] Jaber MA. Intraoral minor salivary gland tumors: a review of 75 cases in a Libyan population. Int J Oral Maxillofac Surg 2006;35:150–4. [13] http://www.prb.org/publications/Datasheets/2006/2006WorldPopulationDataSheet.aspx. [14] Rawashdeh MA, Matalka I. Malignant oral tumors in Jordanians 1991–2001. Int J Oral Maxillofac Surg 2004;33:183–8. [15] Morris RE, Al Mahmeed VE, Gjogov AN, Al Jazaff HG, Al Rashi B. The epidemiology of lip, oral cavity and pharyngeal cancers in Kuwait 1975–1988. J Oral Maxillofac Surg 2000;38:316–9. [16] Ibrahim EM, Satti MB, Al Idrissi HY, Higazi MM, Magbool GM, Al Quorain A. Oral cancer in Saudi Arabia: the role of alqat and alshammah. Cancer Detect Prev 1986;9(3–4):215–8. [17] Shiboski C, Shiboski S, Silverman Jr S. Trends in oral cancer in the United States, 1973–1996. Community Dent Oral Epidemiol 2000;28:249–56. [18] Hindle I, Nally F. Oral cancer: a comparative study between 1962–1967 and 1980–1984 in England and Wales. Br Dent J 1991;170:15–20. [19] Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nandakumar A, et al. Oral cancer in southern India: the influence of smoking, drinking, paan chewing and oral hygiene. Int J Cancer 2002;98:440–5. [20] El Mistiri M, Verdecchia A, Rashid I, El Sahli N, El Mangush M, Federico M. Cancer incidence in eastern Libya: the first report from the Benghazi Cancer Registry, 2003. Int J Cancer 2007;15:392–7. [21] Lu Y, Xuan M, Takata T, Wang C, He Z, Zhou Z, et al. Odontogenic tumors. A demographic study of 759 cases in a Chinese population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86(6):707–14. [22] Daley TM, Wysochi GP, Pringle GA. Relative incidence of odontogenic tumors and oral jaw cysts in a Canadian population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1994;77:276–80. [23] Budhy TI, Soenarto, Yacoob HB, Ngeow WC. Changing incidence of oral and maxillofacial tumours in East Java, Indonesia, 1987–1992. Part 2: Malignant tumours. Br J Oral Maxillofac Surg 2001;39:460–4. [24] Ajayi OF, Adeyemo WL, Ladeinde AL, Ogunlewe MO, Effiom OA, Omitola OG, et al. Primary malignant neoplasms of orofacial origin; a retrospective review of 256 cases in a Nigerian tertiary hospital. Int J Oral Maxillofac Surg 2007;36:403–8. [25] Canto MT, Devesa SS. Oral cavity and pharyngeal cancer incidence rates in the United States, 1975–1998. Oral Oncol 2002;38:610–7. [26] Otoh EC, Johnson NW, Danfillo IS, Adeleke OA, Olasoji HA. Primary head and neck cancers in North-eastern Nigeria. West Afr J Med 2004;23:305–13. [27] Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. New Engl J Med 2001;344(15):1125–31. [28] Sargeran K, Murtumaa H, Safavi SMR, Vehkalahti M, Teronen O. Malignant oral tumors in Iran: ten year analysis on patient and tumor characteristics of 1042 patients in Tehran. J Craniofac Surg 2006;17:1230–3. [29] Burns DM. Nicotine addiction. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. 15th ed., Harrisons principles of internal medicine, vol. 2, 15th ed. Mc Graw Hill Company; 2001: 2574–7. [30] Krutchkoff DJ, Chen J, Eisenberg E, Katz RV. Oral cancer: a survey of 566 cases from the University of Connecticut Oral Pathology Biology Service 1975–1986. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1990;70:192–8. [31] Jovanovic A, Schulten EA, Kostense PJ, Snow GB, van der Waal I. Tobacco and alcohol related to the anatomical site of oral squamous cell carcinoma. J Oral Pathol Med 1993;22(10):459–62. [32] Zain RB. Cultural and dietary risk factors of oral cancer and precancer—a brief overview. Oral Cancer 2001;37:205–10. [33] Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of lip cancer: a review of global incidence. Oral Dis 1999;5:185–95. [34] Marx R, Stern D. Oral and maxillofacial pathology. A rationale for diagnosis and treatment. Quintessence Publishing Co., Inc.; 2003. p. 865–69, 870–75. [35] Wang D, Li Y, Huawei H, Liu L, Wu L, He Z. Intraoral minor salivary gland tumors in a Chinese population: a retrospective study on 737 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104(1):94–100.