the incidence rates of oral cancer are 3.7% for men 
 and 2.6% for women in the sudan . several lifestyle risk factors 
 for the development of oral cancer are familiar , including tobacco products , alcohol , 
 infections , dietary factors , chemical irritants and frank carcinogens . prevalence 
 of oral cancer is 3.2% in sudan and the disease is mainly attributed to n - nitrosamine 
 rich oral snuff consumption . there are mainly 4 smokeless tobacco products : loose 
 leaf or chewing tobacco , snuff , plug tobacco and twist or roll tobacco . chewing 
 tobacco and snuff are by far the most widely distributed types of smokeless tobacco . however , snuff is now 
 habitually used orally by insertion it between lower gum and cheek or lip ( dipping ) 
 . the oral use of snuff in north america and western 
 europe is causally associated with an increased risk for cancer of the oral cavity 
 and pharynx . snuff dipping has also been incriminated as being associated with cancer 
 of the nasal cavity , oesophagus , pancreas , kidney and urinary bladder [ 2 - 6 ] , 
 and other pre - neoplastic changes such as leukoplakia . however , all these risk factors are beyond the scope 
 of the present review . the main goal of this paper was to review the studied risk 
 factors that linked to aetiology of oral cancer in sudan . in this review 33 studies published up to august 
 2012 in the aetiology of oral cancer from sudan were included . they were identified 
 through searches of the medline database , using the keywords : " sudan " , " toombak " , 
 " infection " , " hpv " , " oral hygiene " , " alcohol " , " hot meals " , " cancer " , " oral squamous 
 cell carcinoma " and " risk factors " . papers were also searched among those quoted 
 as references in the retrieved studies , as well as , in a few previous reviews . only 
 papers in english were considered . in the sudan , oral snuff , known locally as toombak , 
 is home - made from finely ground leaves of nicotiana rustica , a tobacco species with 
 a particularly high content of nicotine and minor alkaloids . this tobacco is mixed 
 with natron or atron ( sodium bicarbonate ) ( about 4:1 ) , then water is added to the 
 mixture , and after a period of about 2 hours or longer the mixture , called " saffa " 
 . atron , opposed to lime in other parts of the world , is probably added to toombak 
 for its alkaline effects . it has been shown that at high ph ( 11.0 - 11.8 ) nicotine 
 is completely protonated and its rate of absorption is increased . n - nitrosamines : the study by idris et al .  
 have analyzed the tobacco specific nittrose amine ( tsna ) levels in toombak and found 
 unusually high levels of these tsnas compared to the reported levels in any snuff 
 . these high levels of tsnas found 
 in toombak were partially attributed to the use of tobacco species , nicotiana rustica , 
 and fermentation of toombak at elevated temperature , prolonged storage , and contamination 
 during processing [ 13 - 15 ] . therefore , assuming chronic toombak 
 use , the minimum daily dose of nnk to which these users were exposed was 0.12 - 
 0.44 mg . epidemiological evidence suggests that toombak is 
 a risk factor for cancer of the oral cavity and possibly of the oesophagus in the 
 sudan [ 17 - 19 ] . data from 1,916 cases of oral neoplasms occurring 
 in the sudan in a 16-year period , from january 1970 to december 1985 , were retrieved 
 and analyzed . the study revealed a relatively high frequency of oral neoplasms in 
 comparison with neighbouring countries . squamous - cell carcinoma was the most common 
 oral malignancy ( 66.5% ) , followed by tumours of the salivary gland ( 14.7% ) , neoplasms 
 of non - odontogenic and non - epithelial origin ( 9.6% ) and odontogenic neoplasms ( 8.6% ) . female toombak use 
 is considered social stigma in sudan , consequently the 95% of toombak users were 
 males , which supports its etiological effects . in sweden , snus ( locally known as snus ) , was introduced 
 since the year 1637 . the study by idris et al . compared between snus ( sweden ) and 
 toombak . snus and toombak dippers develop a clinically and histologically characteristic 
 lesion at the site of dipping . snus was associated with a lower risk of cancer of 
 the oral cavity ( relative risk : rr 5 - 6-fold ) compared to high risk of toombak ( rr 
 7.3 - 73.0-fold ) . clinical ( n = 281 ) and histopathological ( n = 141 ) 
 characteristics of toombak - associated oral mucosal lesions detected in an epidemiological 
 study in northern sudan in 1992/93 found parakeratosis , pale surface staining of 
 the epithelium and basal cell hyperplasia were commonly observed , but epithelial 
 dysplasia was infrequent ( 10/141 ) . ultra structural features 
 oral toombak dipper s lesions with distinctive sub epithelial hyaline deposits their 
 bulk is made up of collagen , as typical cross - striated fibrils . the pathogenesis 
 of this deposit could therefore be interpreted as over - production and/or reduced 
 turnover of collagen by resident fibroblasts , which is further altered by the ingredients 
 of toombak . in a study investigated the effects of toombak on 
 primary normal human oral keratinocytes , fibroblasts , and a dysplastic oral keratinocytic 
 cell line , compare to swedish snuff , a potential for toombak , higher than for swedish 
 snuff , to damage human oral epithelium . furthermore , in 
 oscc , apoptosis was associated with bax expression and was unaffected by p53 gene 
 status or toombak use in oscc from the sudan . the study by ibrahim et al .  
 analyzed 14 oral squamous - cell carcinomas ( osccs ) and 8 pre - malignant oral lesions 
 from different sudanese patients for prevalence of mutations in exons 5 to 9 of 
 the p53 gene in relation to toombak - dipping status . osccs ( 14 from sudan , 28 from 
 scandinavia ) , and 3 pre - malignant oral lesions from sudanese non - dippers were used 
 as controls . a statistically significant ( p < 0.05 ) increased incidence in mutations 
 of the p53 gene was found in osccs from toombak dippers ( 93% ; 13/14 ) , as compared 
 with those from non - dippers in sudan ( 57% ; 8/14 ) and in scandinavia ( 61% ; 17/28 ) 
 respectively . several studies from sudan have proved that toombak 
 use is a major risk factor that responsible of high frequencies of potential malignant 
 oral lesions and oral cancers and in particular osccs in the sudan . most of tumours 
 were observed at the site of dip application ( lower lip ) . oral cancer seems to be 
 gender - specific , as the majority of cases were males [ 26 - 31 ] . however , all of the preceded discussed literatures 
 support the criminal role of toombak in the aetiology of oral cancer in the sudan . probably toombak has a major role but it is not alone responsible of oral cancer 
 in the sudan , particularly in the recent years with dramatic increase in overall 
 cancer risk . most oral cancer cases and deaths are due to both 
 individual predisposition , linked to specific genetic characteristics , and exposure 
 to carcinogens , caused by lifestyle behaviours , particularly tobacco . nicotine is only a minor component of tobacco leaves 
 and constitutes about 5% of the total weight of dry plant leaves . when tobacco smoke is inhaled , 25% 
 of the nicotine reaches the brain in about seven seconds . nicotine functions by 
 binding to nicotinic acetylcholine receptors , causing increased heart rate , vasoconstriction , 
 and alertness . nicotine induces dependence among genetically , 
 mentally and socially predisposed individuals with addictive personalities . tobacco carcinogenicity is more than evident and 
 about one fourth of oral cancer cases are attributable to cigarette smoking . specifically , tobacco products are causally linked to a variety of cancers , including 
 those of the lung , oral cavity , nasal cavity , larynx , oropharynx , hypopharynx , oesophagus , 
 stomach , liver , pancreas , bladder , ureter , kidney , cervix , and myeloid leukaemia . more than 60 carcinogens are present in cigarette 
 smoke and at least 16 in unburned tobacco have been identified . the most important 
 are tobacco - specific nitrosamines , such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 
 ( nnk ) and n - nitrosonornicotine ( nnn ) , polycyclic aromatic hydrocarbons in particular , nnk , nnn and pah have been causally 
 linked to oral cancer . few women admit to tobacco use due to cultural norms 
 in the society , and among males the estimated prevalence is around 20% . 
 in most samples from indoor air polluted with environmental tobacco smoke ( ets ) , the highest concentration of an individual tsna is that of nnk . when nonsmokers 
 had remained for up to 2 hours in a test laboratory with high ets pollution , they 
 excreted measurable amounts of nnk metabolites in the urine , indicative of the uptake 
 of tsna . a house to house cross - sectional survey of a random 
 population sample of 4,535 households was performed , as the first survey on tobacco 
 in the sudan . of the 23,367 household members identified , 21,648 ( 92.6% ) eligible 
 individuals were questioned about tobacco use . results showed that , among children 
 and adolescents ( 4 - 17 years ) prevalence of tobacco use was quite low ( 2% , range 
 1 - 2% ) , but there was an abrupt increase up to 25% in late adolescence . among the 
 adult population aged 18 years and older the prevalences of toombak use ( 34% ) and 
 cigarette smoking ( 12% ) among males were significantly higher than among females 
 ( 2.5 and 0.9% , respectively ) . as part of the development of a screening procedure 
 for oral cancer and precancer , exfoliative cytology ( efc ) was applied to 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 ) without 
 prior knowledge of the subjects tobacco exposure . et was ascertained in 29 subjects 
 and could not be ascertained in the remaining 271 . among the 29 subjects with et , 
 there were 11 ( 38% ) toombak dippers , 14 ( 48% ) cigarette smokers and 4 ( 14% ) non - tobacco 
 users . among the 271 subjects without et , there were 89 ( 33% ) toombak dippers , 86 
 ( 32% ) cigarette smokers and 96 ( 35% ) 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 . both in tobacco smoke and smokeless tobacco , carcinogenic 
 n - nitroso compounds ( noc ) are implicated as dna - damaging agents in cancers of the 
 aerodigestive tract and the pancreas . poor oral hygiene was found to contribute 
 to the formation of nitrosamines in the oral cavity . the evidence so far accumulated 
 demonstrates that tobacco habits increase endogenous noc formation , thus adding 
 to the burden of exposure by preformed carcinogenic noc in tobacco products . however , in view of these studies , smoked tobacco 
 has a role in aetiology of oral cancer , but how far this is contributing in oral 
 cancer in sudan and how far it is significant is unknown , since there is lack of 
 data in this context . alcoholic beverages are a heterogeneous group of 
 beverages , with variable number , type and concentration of components . carbon dioxide , minerals ( mostly potassium , phosphates 
 and sodium ) , amino - acids , organic and inorganic acids , polyphenols and carbohydrates 
 are prevailing in beers . alcohols , carbohydrates ( mainly sugar and pectin ) , organic 
 acids , minerals ( mostly potassium , iron , phosphates and calcium ) , polyphenols , vitamins 
 and carbon dioxide are the major wine components , while spirit and liqueur composition 
 is very assorted , with common components being alcohols , acids ( mainly fatty and 
 acetic acid ) , esters , aldehydes , terpenes , ethereal oils and volatile bases . indeed , among 
 individuals consuming 4 - 5 drinks daily , the risk for cancer of the oral cavity 
 is 2 - 3 folds higher than among non - drinkers [ 44 - 47 ] . overall , 7 - 19% oral cancer cases are attributable 
 to heavy alcohol drinking . . 
 the major alcohol metabolising enzymes are alcohol dehydrogenase , that oxidises 
 ethanol to acetaldehyde , and aldehyde dehydrogenase , that detoxifies acetaldehyde 
 to acetate . acetaldehyde is responsible for the oral carcinogenic effect of ethanol , 
 owing to its multiple mutagenic effects on dna . in addition , 
 ethanol is not the only carcinogen present in alcoholic drinks , other minor components , 
 such as nitrosamines , acrylamide , oxidized polyphenols are classified as probable 
 carcinogenic to humans , with animal experiments showing mutagenic activity on oral 
 epithelial cells . since alcohol consumption is considered illegal in 
 sudan , no available data about the relationship between alcoholic beverage consumption 
 and oral cancerous development . the study evaluated cytological atypical changes in apparently 
 healthy oral mucosa exposed to smoking , alcohol , hot meals , and peppers . the features 
 of cytological atypia were verified among 10 individuals , including 5 smokers , 2 
 alcohol users , 2 hot meals and peppers consumers , and one non - exposed . for atypia 
 among tobacco smokers , the adjusted odds ratio ( or ) and the 95% ci were found to 
 be 2 ( 0.246 - 16.24 ) . increased keratinisation was detected among 27 ( 45% ) of the 
 smokers ( p < 0.0001 ) , 17 ( 32.7% ) of the pepper and hot meals consumers ( p < 0.005 ) , 
 4 ( 11.8% ) of the alcohol consumers , and among 2 ( 3.7% ) of the non - exposed group . statistical analyses revealed a greater mean number of agnors per nucleus in smokers 
 ( 3.68 ) followed by ( 2.82 ) alcohol consumers , compared to the habitual peppers and 
 hot meal consumers ( 2.28 ) and the non - exposed group ( 2.00 ) . however , no available data about alcoholic consumers 
 in the sudan , approximately 95% of the habitual use to drink in hide , since it is 
 considered as illegal and social stigma . consequently , nobody can estimated or even 
 imagine its burden as a risk contributes to the aetiology of oral cancer in the 
 sudan . human papilloma viruses ( hpv ) infection the hpv are a large family of non - enveloped dna viruses , 
 mainly associated with cervical cancers . recent epidemiologic evidence has suggested 
 that hpv may be an independent risk factor for oropharyngeal cancers . hpv has a wide disease spectrum affecting the cutaneous and mucosal areas of the 
 body , ranging from benign common warts to invasive carcinoma . hpv infections have 
 been reported in a number of body sites , including the anogenital tract , urethra , 
 skin , larynx , tracheobronchial mucosa , nasal cavity , paranasal sinus , and oral cavity 
 . hpv is one of the most prevalent infections in the world 
 with several new cases diagnosed every year . there are more than 120 genetically different , 
 yet closely related hpvs that are referred to as genotypes . by definition , each 
 type is defined by having less than 90% dna base pair homology with any other identified 
 hpv type . the hpv genome encodes dna sequences for six early 
 ( e1 , e2 , e4 , e5 , e6 , and e7 ) proteins associated with viral gene regulation and 
 cell transformation , two late ( l1 and l2 ) proteins which form the shell of the virus , 
 and one region of regulatory dna sequences . the different hpv types are characterized 
 by genotypic variations in the dna base - sequences of e6 and e7 . it is these genotypic 
 differences that permit stratification of the virus oncogenic phenotype into high , 
 intermediate- , and low - risk types . in the case of high - risk hpv infection and under 
 favourable conditions , the viral genome is integrated into the host genome , which 
 is the necessary event for the keratinocytes immortality . during this process of 
 integration , the circular form of viral genome breaks at the level of the e1 and 
 e2 regions , never at the level of the e6 or e7 region . different studies have shown 
 that the integrated part of the genome corresponds to e1 , e6 , and e7 , while the 
 regions from e2 to e5 are lost and are not transcribed in the tumours . the loss 
 of e2 during this process of integration produces the loss of e6 and e7 control . therefore , the sequences e6 and e7 are directly involved in the cellular cycle by 
 inhibiting the normal functions of p53 and prb , respectively . the protein p53 is 
 known as the " genome s guard " and in the case of dna damage , the p53 can provoke 
 the arrest of cellular division and assure the time necessary for dna repair . if 
 damage can not be repaired , p53 is able to induce the programmed cellular death and 
 prevent the propagation of dna damage in subsequent generations of cells . in the 
 case of other types of tumours , p53 is usually mutated and acts as a real oncogene . 
 in the case of hpv infection , e6 suppresses the properties of p53 gene product , 
 achieving the functional equivalent of the two hits required to knock out both alleles 
 of a tumour suppressor gene . the e7 
 protein interacts with retinoblastoma protein ( prb ) , which is the crucial factor 
 for the cellular cycle control . this interaction causes the release of the transcription 
 factor e2f , which is now free to act and can stimulate the cellular division . e7 
 is also able to bind and inactivate the protein kinase inhibitors p21 and p27 and 
 can interact with different proteins whose significance has still not been determined 
 . hpv has gained much interest recently , 
 because it is accepted as important correlates of cervical cancer . oral hpv infections 
 have not been studied to the degree as those of the genital tract , although the 
 evidence of association between certain tumours and hpv infection today is indisputable . oncogenic hpvs are associated with oral malignancies , but its prevalence varies 
 widely in different studies . although study results are mixed , it seems possible 
 that smoking and alcohol use may interact with hpv infection to increase a person s 
 risk of oral cancer . so , oral hpv infections need to be studied and investigated 
 deeply so that it can guide us for future cancer prevention programs , including 
 oral hpv vaccination for oral hpv infections . nevertheless , few studies have investigated the role 
 of viruses in general and hpv in particularly in the aetiology of oral cancer in 
 the sudan . the first study investigated potentially malignant oral mucosal lesions 
 from sudanese patients ( 9 hyperplasias/40 dysplasias ) . hpv was found in only 2 sudanese 
 cases , both of which harboured both type 6 and type 11 : both these cases demonstrated 
 mild epithelial dysplasia . another study from sudan investigated 
 a total of 40 cases ( patients with osccs ) and 15 controls ( patients with benign 
 lesions ) were included in the study . the cases included ; carcinomas of the oral 
 cavity proper , carcinomas of the lip vermilion . hpv was detected among 6 ( 15% ) of 
 the cases , four were hpv type 16 and two were hpv type 18 . a recent study from sudan reported the presence of hpv in head and neck cancers 
 ( hncs ) in general and in oral in particular . hpv16 was the most prevalent type , with single infections present in 3/6 ( 50% ) cases , 
 whereas hpv18 and hpv33 were detected in 2/6 ( 33% ) and 1/6 ( 17% ) , respectively . hpv infections were detected in 3 ( 50% ) cases of oral cavity and 3 ( 50% ) cases of 
 pharynx . furthermore , very limited studies have investigated 
 the role of other viruses such as , epstein - barr virus ( ebv ) and herpes simplex virus 
 ( hsv ) in the aetiology of oral cancer in sudan beside hpv . using pcr / dna sequencing , 
 a study has investigated the prevalence of hpv , hsv and ebv dna in brush biopsies 
 obtained from 150 sudanese toombak dippers and 25 non - toombak dippers in formalin - fixed 
 paraffin - embedded tissue samples obtained from 31 patients with oral dysplasias 
 ( 25 toombak users and 6 non - users ) , and from 217 patients with oral cancers ( 145 
 toombak users and 72 non - users ) . in the brush tissue samples from toombak users , 
 hpv was detected in 60 ( 40% ) , hsv in 44 ( 29% ) and ebv in 97 ( 65% ) of the samples . the corresponding figures for the 25 samples from non - users were 17 ( 68% ) positive 
 for hpv , 6 ( 24% ) positive for hsv and 21 ( 84% ) for ebv . the formalin - fixed samples 
 with oral dysplasias were all negative for hpv . in the 145 oral cancer samples from 
 toombak users , hpv was detected in 39 ( 27% ) , hsv in 15 ( 10% ) and ebv in 53 ( 37% ) 
 of the samples . the corresponding figures for the samples from non - users were 15 
 ( 21% ) positive for hpv , 5 ( 7% ) for hsv and 16 ( 22% ) for ebv . these findings illustrate 
 that prevalence of hsv , hpv and ebv infections are common and may influence oral 
 health and cancer development . these observations warrant further studies involving 
 toombak - associated oral lesions , to uncover the possible mechanisms of these viral 
 infections in the development of oral cancer , and the influence of toombak on these 
 viruses . in another study investigated the prevalence of 
 hpv , hsv and ebv in 155 osccs from eight different countries from different ethnic 
 groups , continents and with different socioeconomic backgrounds , the highest prevalence 
 of hpv was seen in sudan ( 65% ) . genetic factors have enhancing roles in many cancers 
 including oral cancer . limited studies have dealt with the investigation of association 
 between genetic factors and level of risk for development of oral cancer in sudan . 
 in a study aiming to explore possible range of gene expression profiles in head 
 and neck squamous cell carcinomas ( hnscc ) and pair wised normal controls from sudanese 
 ( n = 72 ) and norwegian ( n = 45 ) patients using a 15k cdna microarray and to correlate 
 the findings with clinicopathologic variables . analysis of the two population 
 groups revealed a common set of 73 genes within three main biological pathways . this indicates that the development of hnsccs is mediated by similar biological 
 pathways regardless of differences related to race , ethnicity , lifestyle , and/or 
 exposure to environmental carcinogens . of particular interest , however , was the 
 valuable association of gene expression signature found with toombak use and anatomic 
 site of the tumours . the prevalence of mutations in exons 2 and 3 of the 
 s100a4 gene was analyzed in the 14 osccs from toombak - dippers and in 25 cases of 
 osccs from the control non - snuff - dippers . of the 14 osccs investigated from toombak - dippers , 
 mutations in the p21waf1 exon 2 were found in 43% ( 6 out of 14 ) , compared to 14% 
 ( 2 out of 14 ) , 22% ( 6 out of 27 ) and 14% ( 5 out of 35 ) found in those from non - snuff - dippers 
 from the sudan , scandinavia and the usa / uk , respectively . the study by lazarus et al .   suggested that toombak components 
 such as tsnas may induce p53 mutations in head and neck sccs and are likely contributors 
 to the tobacco - induced carcinogenic load in humans . a recent study investigated the prevalence of p53 
 codon 72 polymorphism in brush biopsies obtained from a sudanese population . a total 
 of 174 individuals were included in the study ; chronic toombak users ( n = 152 ) and 
 non - users ( n = 22 ) . dna was extracted from all the samples and genotyped for the 
 codon 72 polymorphism by polymerase chain reaction / restriction fragment length polymorphism . the arg / pro genotype was found in 53% of the 174 study participants , compared to 
 21% found with arg / arg and 26% found with pro / pro . stratifying by toombak use , 28 
 ( 18% ) , 45 ( 29% ) and 79 ( 52% ) of the 152 samples from toombak users had arg / arg , 
 pro / pro and arg / pro respectively , compared to 9 ( 41% ) , 0 ( 0% ) and 13 ( 59% ) found 
 in the 22 samples from non users . the differences between the samples from toombak 
 users and non users in arg / arg and pro / pro codon 72 polymorphism and hpv infection 
 were statistically significant ( p < 0.05 ) . the study indicated that a high prevalence 
 of the genotype arg / pro at the p53 codon 72 may contribute to susceptibility to 
 oscc , especially in combination with the use of carcinogenic tobacco - specific nitrosamine 
 ( tsna)-rich toombak . in another study , 9 genes related to 
 apoptosis , cell cycle regulation and intermediate filament proteins were selected 
 and their differential expression status was examined by real - time quantitative 
 rt - pcr in 26 samples of sudanese osccs and their matched normal controls . the mrna levels of bcl2 , keratin 
 1 , keratin 13 and p53 were significantly lower and the level of survivin was significantly 
 higher in the oscc samples of the toombak users compared to their paired control 
 samples . a significant down - regulation in keratin 1 and keratin 13 expression levels 
 was found in the oscc samples of the non - toombak users compared to their normal 
 control samples . the differential expression of genes related to apoptosis , cell 
 cycle regulation and types i and ii keratin could be useful diagnostic markers and 
 provide valuable information for the understanding of oral malignancy in relation 
 to toombak use . besides tobacco and alcohol , other risk factors have 
 been studied in relation to oral cancer in sudan . among these factors , diet and 
 nutrition so far there is a lack of studies focusing on the prevalence of a wide spectrum 
 of oral mucosal lesions ( oml ) in patients with dermatologic diseases . this is noteworthy 
 as skin lesions are strongly associated with oral lesions and could easily be neglected 
 by dentists . a study from sudan found that oml were frequently diagnosed in skin 
 diseased patients and varied systematically with age , gender , systemic condition 
 and use of toombak . epidemiological studies conducted in various populations 
 reported an inverse association between intake of fruit and vegetables and the risk 
 of cancer of the oral cavity . thus , fruit and vegetables 
 appear to be the most consistent favourable dietary aspect on oral and pharyngeal 
 neoplasm . in a network of studies from italy , about 20 - 25% of cancers of the oral 
 cavity and pharynx were attributed to low fruit and vegetable consumption , and the 
 population attributable risk , rose to 85 - 95% when tobacco and alcohol consumption 
 were also considered . the evidence on the role of milk and dairy products , 
 as well as coffee and tea , on the risk of cancer of the oral cavity and pharynx 
 is scanty , and does not indicate any consistent association . , none of these factors has been investigated in the sudan . as sudan is very 
 large country with different climates toombak plays a major role in the aetiology of oral 
 cancer in sudan , since it is a potent carcinogenic , as well as it acts as a synergistic 
 factor enhances the carcinogenesis of other etiological factors , such as genetic 
 factors and viruses . the role of human papilloma virus in aetiology of oral cancer 
 is reasonable , but the question how far is it without toombak ? the real contribution 
 of other risk factors such as viruses other than human papilloma virus , smoked tobacco 
 and alcohol still need more investigation other factors that have increased risk 
 or reverse risk need more investigation .