tobacco use is one of the main factors that can lead to cancers of the oral cavity and pharynx .
there are many types of smokeless tobacco products such as chew , chewpoos , chits , chewsky , dip , smokeless tobacco keratosis , flab , chowers , snuff dipper , guy , snus or nass , which can be used by placing and chewing a small amount of the substance between the cheek and gum or teeth . in europe and north america , chewing tobacco and snuff are two major products .
both , moist and dry snuff exists in this area , such that moist snuff is usually used in scandinavia and the usa .
it is generally placed under the upper lip , lower lip or kept in the buccal gingival area , but dry snuff is placed in the oral cavity or administered through the nose .
snus ( called  nass  in iran , afghanistan and pakistan ) or swedish snuff is used by placing it under the lip for extended periods of time .
it is a moist powder tobacco product produced from a variant of dry snuff in the early nineteenth century in sweden .
this material is a mixture of pan prague , coarse grains and red trees along with tobacco leaf , lime , ash aromatic spices , saccharin and various oils . during recent decades
, the use of smokeless tobacco has increased in the middle east , particularly among teenagers and young adults .
the prevalence of smokeless tobacco in relation to age reflects major changes over the decades in the use of smokeless tobacco . in 1970 , 2.2% of white male adults aged 18 to 24 years used chewing tobacco or snuff .
the prevalence was higher at successively older ages , peaking at 11.8% among white men 65 years or older . in 1991 ,
the age trends were reversed , with 10.4% of 18 - 24 year - olds using the products and fewer older persons using them : 7.9% of 25 - 34 year - olds , 5.4% of 35 - 44 year - olds , 3.8% of 45 - 64 year - olds , and 5.5% of individuals 65 years of age and older . the relation between use of smokeless tobacco and cancer
was noted as early as 1761 , when a british physician described nasal  polyposes  , probably nasal cancer in several of his patients , which he attributed to the use of snuff through the nose .
the cancers often occurred precisely where tobacco had routinely been placed in the lower half of the mouth and in the buccal mucosa or gums . here
we report a series of cases of squamous cell carcinoma and verrucous carcinoma occurring in the users of snus , who referred to the department of oral medicine in kerman dental school .
a 78-year - old iranian female was referred to the department of oral medicine , kerman dental school , by her dentist for evaluation of an exophytic lesion on the right buccal mucosa , which had been noticed 2 months previously .
in addition , the patient had a snus habit for the past 15 years in the right mandibular vestibule but no alcohol consumption . on examination
, there was a tender firm exophytic lesion with induration , measuring 8 cm by 4 cm , on the right buccal mucosa .
the surface of the lesion was verrucous with a white color and no associated lymphadenopathy [ figure 1 ] . a exophytic lesion with measuring 8 cm by 4 cm at the right of the buccal mucosa .
the surface of lesion is verrucous a diagnosis of verrucous carcinoma with differential diagnosis of a squamous cell carcinoma was made . under local anesthesia ,
histological examination of the excised tissue showed features of a poorly differentiated verrucous carcinoma . in view of the diagnosis of verrucous carcinoma , further investigations including chest radiography and hematological and biochemical blood tests yielded negative results .
further , histological examination of the main specimen confirmed the presence of a verrucous carcinoma with parakeratin and the wide and elongated rete ridges that appear to push into the underlying connective tissue [ figure 2 ] .
a year later , the patient passed away despite removal of the lesion and a relatively good response to treatment . a verrucous carcinoma with parakeratin and the wide and elongated rete ridges that appear to push into the underlying connective tissue a 53-year - old female presented for routine examinations with his general dental practitioner , complaining of a sore area on the right side of the buccal mucosa , present for about 4 weeks .
the patient had hypertension for the past 10 years and had become addicted to opium 15 years previously .
she had a snus habit from 5 year ago in the right mandibular vestibule with no alcohol consumption .
the practitioner diagnosed a leukoplakia and the patient was referred to the dental school for biopsy . in the intraoral examination , a 5 cm - diameter white verrucous area extended from the right buccal mucosa into the alveolar ridge , which was tender to palpation .
the tissue proximal to the lesion was erythematous and atrophic in appearance with indurations [ figure 3 ] .
a verrucous area extended from the right buccal mucosa into the alveolar ridge , which tender to palpation .
the tissue proximal to the lesion is erythematous and atrophic in appearance with indurations the lesion was biopsied and histological examination of the excised soft tissue showed features of a early squamous cell carcinoma with some cell degeneration , keratin pearls , nests and cords of malignant epithelial cells with wide cytoplasm , round or oval nuclei , with prominent nucleoli and mitotic figures [ figure 4 ] . a early squamous cell carcinoma with some cell degeneration , keratin pearls , nests and cords of malignant epithelial cells with wide cytoplasm , round or oval nuclei , with prominent nucleoli and mitotic figures the patient underwent total excision of the lesion with reconstruction using a split skin graft .
a 35-year - old female was referred urgently having presented to her general medical practitioner complaining of an ulcer on her tongue of about 2-month duration .
the patient was complaining of an ulcer on the right side of her tongue , which had previously been asymptomatic but had begun to cause occasional discomfort as it increased in size .
previous medical history revealed that the patient was suffering from hyperthyroidism . otherwise , her medical history was clear , and the patient had a snus habit for the previous 3 years in the right mandibular lingual vestibule .
intraorally , there was evidence of a crater - like ulcer ( prominent border and depressed base ) on the right lateral border of the tongue extending into the dorsal surface of the tongue with a diameter of 6 cm , which was tender and indurated [ figure 5 ] .
a crater like ulcer on the right lateral border of the tongue that extending into dorsal surface of the tongue an incisional biopsy was performed , which revealed poorly differentiated squamous cell carcinoma histopathologically .
ct revealed two abnormal nodes in the right submandibular region , which were needle - biopsied ; metastatic squamous cell carcinoma was detected . following surgery and radiotherapy
an 82-year - old female , from zahedan province , was referred by her general dental practitioner in relation to a complaint of a growth in the lower right alveolar left region since 3 months previously .
the patient had smoked up to 5 cigarettes per day for the past 20 years and had the habitual use of snus 4 - 5 times a day for the past 20 years in the left mandibular vestibule .
a solitary submandibular lymph node was palpable on the left side , measuring 4 cm in size , which was tender and hard boney in consistency and fixed .
intraorally , an ulcero - proliferative lesion was evident on the left mandibular ridge area , measuring about 4  5 cm in size .
it was irregular in shape with rolled - out edges extending to the floor of the mouth .
the lesion was tender on palpation with an indurated base ; in addition , there was evidence of a crater - like ulcer on the left vermilion border of the lip [ figures 6 and 7 ] .
an ulcero - proliferative lesion in the left mandibular ridge area a crater like ulcer on the left vermilion border of lip incisional biopsy of the lesion was performed , which provided a histopathological diagnosis of poorly differentiated squamous cell carcinoma .
a 78-year - old iranian female was referred to the department of oral medicine , kerman dental school , by her dentist for evaluation of an exophytic lesion on the right buccal mucosa , which had been noticed 2 months previously .
in addition , the patient had a snus habit for the past 15 years in the right mandibular vestibule but no alcohol consumption . on examination
, there was a tender firm exophytic lesion with induration , measuring 8 cm by 4 cm , on the right buccal mucosa .
the surface of the lesion was verrucous with a white color and no associated lymphadenopathy [ figure 1 ] . a exophytic lesion with measuring 8 cm by 4 cm at the right of the buccal mucosa .
the surface of lesion is verrucous a diagnosis of verrucous carcinoma with differential diagnosis of a squamous cell carcinoma was made . under local anesthesia ,
histological examination of the excised tissue showed features of a poorly differentiated verrucous carcinoma . in view of the diagnosis of verrucous carcinoma , further investigations including chest radiography and hematological and biochemical blood tests yielded negative results .
further , histological examination of the main specimen confirmed the presence of a verrucous carcinoma with parakeratin and the wide and elongated rete ridges that appear to push into the underlying connective tissue [ figure 2 ] .
a year later , the patient passed away despite removal of the lesion and a relatively good response to treatment . a verrucous carcinoma with parakeratin and the wide and elongated rete ridges that appear to push into the underlying connective tissue
a 53-year - old female presented for routine examinations with his general dental practitioner , complaining of a sore area on the right side of the buccal mucosa , present for about 4 weeks .
the patient had hypertension for the past 10 years and had become addicted to opium 15 years previously .
she had a snus habit from 5 year ago in the right mandibular vestibule with no alcohol consumption .
the practitioner diagnosed a leukoplakia and the patient was referred to the dental school for biopsy . in the intraoral examination , a 5 cm - diameter white verrucous area extended from the right buccal mucosa into the alveolar ridge , which was tender to palpation .
the tissue proximal to the lesion was erythematous and atrophic in appearance with indurations [ figure 3 ] . a verrucous area extended from the right buccal mucosa into the alveolar ridge , which tender to palpation .
the tissue proximal to the lesion is erythematous and atrophic in appearance with indurations the lesion was biopsied and histological examination of the excised soft tissue showed features of a early squamous cell carcinoma with some cell degeneration , keratin pearls , nests and cords of malignant epithelial cells with wide cytoplasm , round or oval nuclei , with prominent nucleoli and mitotic figures [ figure 4 ] . a early squamous cell carcinoma with some cell degeneration , keratin pearls , nests and cords of malignant epithelial cells with wide cytoplasm , round or oval nuclei , with prominent nucleoli and mitotic figures the patient underwent total excision of the lesion with reconstruction using a split skin graft .
a 35-year - old female was referred urgently having presented to her general medical practitioner complaining of an ulcer on her tongue of about 2-month duration .
the patient was complaining of an ulcer on the right side of her tongue , which had previously been asymptomatic but had begun to cause occasional discomfort as it increased in size .
previous medical history revealed that the patient was suffering from hyperthyroidism . otherwise , her medical history was clear , and the patient had a snus habit for the previous 3 years in the right mandibular lingual vestibule .
intraorally , there was evidence of a crater - like ulcer ( prominent border and depressed base ) on the right lateral border of the tongue extending into the dorsal surface of the tongue with a diameter of 6 cm , which was tender and indurated [ figure 5 ] .
a crater like ulcer on the right lateral border of the tongue that extending into dorsal surface of the tongue an incisional biopsy was performed , which revealed poorly differentiated squamous cell carcinoma histopathologically .
ct revealed two abnormal nodes in the right submandibular region , which were needle - biopsied ; metastatic squamous cell carcinoma was detected . following surgery and radiotherapy
an 82-year - old female , from zahedan province , was referred by her general dental practitioner in relation to a complaint of a growth in the lower right alveolar left region since 3 months previously .
the patient had smoked up to 5 cigarettes per day for the past 20 years and had the habitual use of snus 4 - 5 times a day for the past 20 years in the left mandibular vestibule .
a solitary submandibular lymph node was palpable on the left side , measuring 4 cm in size , which was tender and hard boney in consistency and fixed .
intraorally , an ulcero - proliferative lesion was evident on the left mandibular ridge area , measuring about 4  5 cm in size .
it was irregular in shape with rolled - out edges extending to the floor of the mouth .
the lesion was tender on palpation with an indurated base ; in addition , there was evidence of a crater - like ulcer on the left vermilion border of the lip [ figures 6 and 7 ] .
an ulcero - proliferative lesion in the left mandibular ridge area a crater like ulcer on the left vermilion border of lip incisional biopsy of the lesion was performed , which provided a histopathological diagnosis of poorly differentiated squamous cell carcinoma .
the present study presented 4 cases of oral cancer occurring in the users of snus .
oral carcinoma in these patients had occurred at anatomic locations where this material is routinely placed . a recent evaluation by the international agency for research on cancer ( iarc ) has confirmed that smokeless tobacco is also carcinogenic .
a recent meta - analysis showed a two - fold increase in risk of oral cancer with the use of smokeless tobacco in the united states and canada , a five - fold risk increase for india and other asian countries and a seven - fold risk increase in sudan . no risk increase for oral cancer
was shown with smokeless tobacco use in the nordic countries . in the uk and europe ( with the notable exception of sweden )
the use of smokeless tobacco is rare except in minority ethnic groups . in the usa
, it is a major problem with 6% of the adult male population as regular users . in some areas , particularly the southern states ,
the prevalence is much higher with up to one - third of young men using smokeless tobacco .
the primary cause of the very high incidence of oral cancer in south asia is the widespread habit of chewing betel quid ( or paan ) and related areca nut use ( areca nut is the seed of the fruit of the oriental palm , areca catechu ) .
chewing betel is thought to date back to at least 2000 years and worldwide an estimated 200 - 400 million people practice the habit .
the components of the betel quid vary between different populations but the main ingredients are the leaf of the vine , piper betel , areca nut , slaked lime ( calcium hydroxide ) and spices .
areca nut is carcinogenic to humans and the risk of oral cancer is increased with chewing of paan without tobacco , although the risk is higher for paan - containing tobacco . as with smoking tobacco ,
the risk is dependent on dose and duration of use . among asian communities in the uk , bangladeshis are the most likely to retain the habit of betel quid chewing with 9% of men and 16% of women using smokeless tobacco .
therefore , smokeless tobacco use occurs in many cultures throughout the world , resulting in the incidence of oral cancers in these countries .
for example , in india and other asian countries , smokeless tobacco in combination with areca nut , piper betel leaf , lime , and other ingredients has been strongly linked to oral cancer risk .
recent carefully conducted studies outside of the us continue to indicate that tobacco used in a variety of unsmoked forms confers an oral cancer risk on the user .
the extent of cancer risk might depend on the products or combinations of products used or the way the user takes the product .
therefore , the risk of oral cancer increases with an increase in the product dose .
snus ( nass ) or swedish snuff , is a moist tobacco powder product extracted from a variant of dry snuff in the early nineteenth century in sweden ; it is consumed by placing it under the lip for extended periods of time .
nass is a mixture of tobacco , ash , cotton oil , and lime . in some areas where
nass is taken orally , such as in the central asia , the prevalence of leukoplakia is high , and oral cancer incidence is moderately high relative to other former soviet republics .
three studies were identified that have attempted to understand the cellular mechanisms involved in snuff - induced epithelial changes using oral tissues or cells .
these studies examined the effect of swedish snuff on indicators of cellular proliferation ( e.g. , ki-67 ) and on tumor suppressor and differentiation markers ( e.g. , p53 tumor suppressor gene ) .
this study shows overexpression of ki-67 protein and mutant tumor suppressor p53 protein in the biopsy samples from the snus users and no expression in the control biopsies . also , merne and colleagues evaluated the expression of proteins involved in cell proliferation ( ki-67 , pcna ) , cell cycle regulation ( p53 , p21 ) , and keratins in biopsy specimens from 14 men with sil to 12 biopsy specimens from normal buccal mucosa of men who had never used any type of tobacco products .
loose non - fermented scandinavian moist snuff  and three were also using portion - packed snuff .
in addition , in the assessment of the epidemiologic evidence on carcinogenicity of smokeless tobacco , it is of interest to consider some local effects in the oral cavity . oral leukoplakia is a common finding in snuff users and is sometimes referred to as 
snuff dipper 's lesion. there is a close correlation between exposure ( duration and intensity ) and prevalence , as well as severity of lesions .
the prevalence of micronuclei and other nuclear anomalies is increased in the oral mucosa of snuff users , and the tumor suppressor gene p53 appears to accumulate in oral leukoplakias of snuff users .
a large number of case reports have described oral carcinomas in smokeless tobacco users , occurring at anatomic locations where tobacco is routinely placed . in the mid-1980s , it was concluded from a large number of literature reviews that smokeless tobacco is a cause of oral cancer in humans .
these evaluations relied on case reports and epidemiologic studies in humans and on laboratory studies demonstrating that n - nitrosamine compounds are present in high levels in smokeless tobacco and that these compounds produce cancer in laboratory animals . based on evidence from smokeless tobacco manufacturing statistics ,
the renewed popularity of smokeless tobacco among youth started in the late 1960s and early 1970s .
concern has been expressed that this trend could lead to an epidemic of oral cancers among young men .
a total of 6 case - control studies are available from sweden and the usa on oral snuff use and oral cancer .
one early swedish study indicated an increased risk of buccal and gum cancer in snuff users .
three of the us studies provided evidence of an association between snuff use and oral cancer .
cohort studies on the use of snuff and oral cancer provide inconclusive evidence , but the interpretation is often difficult because of limited statistical power . the data from scandinavia and the us on smokeless tobacco and cancer of sites other than the oral cavity are relatively sparse .
for carcinoma of the upper digestive tract and pancreas , excess risks have been reported , but the evidence is not conclusive . in india , afghanistan and pakistan ,
relative risks exceeding 10 may be observed in regular users , indicating that a substantial proportion of the oral cancers are attributed to the exposure in populations where the habits are widespread .
in addition , two of their patients had other risk factors similar to smoked tobacco consumption and addicted to opium , which might probably cause oral cancer .
although , cancer in these patients had occurred at anatomic locations where this material is routinely placed , oral cancer most commonly involves the tongue and floor of the mouth .
evidence from human population shows that smokeless tobacco users have risks of cancer several times higher than those of nonsmokers .
finally , preliminary work on cancers in other anatomic sites suggests that smokeless tobacco may also be related to other upper digestive tract cancers .
 snus ( nass ) is a form of snuff used in a similar manner to american dipping tobacco , but it does not typically result in a need for spitting . 
 possible hazards associated with this material include malignant and premalignant lesions in the oral cavity and gastrointestinal tract . 
 the use of smokeless tobacco has increased in the middle east in recent decades , particularly among teenagers and young adults . 
 therefore , practitioners must be able to recognize malignant and premalignant lesions . although , an estimated 10 - 25% of the world 's population uses smokeless tobacco , this practice is virtually unknown in iran . 
 the aim of this study is to report a series of cases of squamous cell carcinoma and verrucous carcinoma occurring in the users of snus , who referred to the department of oral medicine in kerman dental school . 
INTRODUCTION
CASE REPORTS
Case 1
Case 2
Case 3
Case 4
DISCUSSION
CONCLUSION