J Clin Exp Dent. 2018;10(4):e396-401.

Risk factors for Oral Cancer

Journal section: Oral Medicine and Pathology doi:10.4317/jced.54618

Publication Types: Research http://dx.doi.org/10.4317/jced.54618

Risk factors of Oral cancer- A hospital based case control study

Natasha Azhar 1, Maheen Sohail 1, Fareeha Ahmad 1, Shaheen Ahmed 1, Soofia Jamil 1, Nouman Mughal 2, Hira
Salam 1

1
Dow International Dental College, Dow University Of Health Sciences
2
Dow International Medical College, Dow University Of Health Sciences

Correspondence:
Address: B-70, Block-A
KDA Officers’ Society, Karachi, Pakistan
[email protected]

Azhar N, Sohail M, Ahmad F, Ahmed S, Jamil S, Mughal N, Salam H.

Received: 05/01/2018 Risk factors of Oral cancer- A hospital based case control study. J Clin
Accepted: 14/03/2018
Exp Dent. 2018;10(4):e396-401.
http://www.medicinaoral.com/odo/volumenes/v10i4/jcedv10i4p396.pdf

Article Number: 54618 http://www.medicinaoral.com/odo/indice.htm

© Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488
eMail: [email protected]
Indexed in:
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Abstract
Background: Oral cancer is a highly prevalent malignancy in Pakistan. Among various risk factors associated with
this neoplasm, habits such as smoked and smokeless tobacco usage, betel quid, and betel nut consumption are the
major culprits in our society. In the present study, we aimed to ascertain prevalent risk factors for OC in our popu-
lation and to compare our findings with healthy controls to establish their significance.
Material and Methods: A hospital-based case control study was conducted at Dow University of Health Sciences,
Pakistan from January 2015 – September 2016. Information pertaining to unhealthy oral habits was obtained from
62 oral cancer patients (cases) and 62 healthy controls on specifically designed proforma by the principal investi-
gator.
Results: Smokeless tobacco is strong, independent risk factor for oral cancer development in our study population.
Buccal mucosa is the predominantly affected site (71%) which corresponds with high smokeless tobacco use. All
studied habits increase risk of oral cancer as demonstrated by high odds ratio.
Conclusions: Despite advancement in our knowledge and understanding of carcinogenic potential of these hazar-
dous substances not enough efforts have been put forth to effectively control their widespread sale and consump-
tion, particularly by the youth in our society.

Key words: Betel Quid, Gutka, Oral Cancer Risk, Smokeless Tobacco.

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J Clin Exp Dent. 2018;10(4):e396-401. Risk factors for Oral Cancer

Introduction In the present study, we aimed to ascertain prevalent risk

Head and neck cancers rank third in most common malig- factors for OC in our population and to compare our fin-
nancies encountered in both genders globally. A subtype dings with healthy controls to establish their significan-
of head and neck cancers is oral cancer (OC), which is ce. We predicted that frequency of consumption would
described as a cancerous growth in the mouth (1). Each be directly proportional to OC incidence. We also ex-
year, over 450,000 patients are diagnosed with OC world- pected participants consuming two or more of these pro-
wide (2). In the last decade, researchers have observed an ducts simultaneously to experience a synergistic effect.
increase in incidence in younger patients, especially with
cancers involving the tongue (3). OC has variable geo- Material and Methods
graphic distribution, being prevalent in Asian countries, A hospital-based case control study was conducted in
particularly South and Southeast Asia (4). the Dental outpatient department (OPD) at Dow Inter-
OC embodies a plethora of malignances including, but national Medical and Dental College (DIDC) in Kara-
not limited to squamous cell carcinoma (SCC), basal chi, Pakistan from January 2015 until September 2016.
cell carcinoma (BCC), verrucous carcinoma, nasophary- Biopsy proven OC patients receiving treatment at Oral
ngeal carcinoma (NPC), malignant melanoma, amelo- Surgery OPD at DIDC were enlisted in the study as ca-
blastoma, mucoepidermoid carcinoma etc. An astoun- ses, whereas healthy patients coming for routine dental
ding majority (~95%) of malignancies diagnosed in oral checkup at Oral Diagnosis department during study pe-
cavity are SCC originating in the mucosa lining mouth, riod were recruited to participate in the study as controls.
tongue and lips whereby latter two are most commonly Informed consent was obtained before initiation of vo-
recorded sites (5-7). lunteering participants.
Owing to grim deficiency in public awareness and scar- A case was defined as patients with histologically confir-
city of affordable screening tools, an alarming capaci- med OC visiting DIDC during study period. The control
ty of OC patients remain undetected until the disease group comprised of age-matched patients who visited
has greatly advanced (8). Clinical presentation can be the Department of oral diagnosis during the study period
non-specific and exhibits substantial variation also hin- and did not have any significant medical history, inclu-
dering diagnosis. OC may present as skin lesions, mu- ding any malignancies or premalignant lesions. People
cosal ulcerations, a lump in the neck or anywhere in the with any other malignancy and comorbidities were ex-
oral cavity, and hyperpigmentation or depigmentation of cluded.
mucosa. Three well-recognized presentations include a Sample size was calculated with the help of expert opi-
white patch (leukoplakia), a red patch (erythroplakia) nion. The sample size was calculated as 62 cases and
or as a red and white patch (speckled leukoplakia) on 62 controls. Allocation ratio was kept as 1:1, hence for
oral mucous membrane, which is usually painless in its every case there was, one control was selected.
beginning stages (9). A burning sensation may be also The investigator personally interviewed cases and con-
be felt by the patient when lesion reaches an advanced trols by using a structured questionnaire. The question-
stage along with dysphagia (9). naire was validated using expert opinion and pre-tested
Pakistan is burdened with one of the highest incidence prior to its use in the field. Informed consent was ob-
rates of OC in the world with strong male preponderance tained from all participants before data collection. Me-
(10). Several risk factors have been established that con- dical ethics approval for this study was obtained from
tribute to observed prevalence trends in our population, Institutional Review Board (IRB) of Dow University of
including specific habits such as tobacco, alcohol, paan Health Sciences (DUHS). The questionnaire included
(betel quid), smokeless tobacco (including chewing to- demographic information for the correlation of patients’
bacco and snuff), and betel nut consumption rendering age, gender, medical history and date of diagnosis. The
population bearing lower socioeconomic status more second part of the questionnaire included questions on
susceptible to OC. Simultaneous consumption of some oral hygiene practices and anticipated risk factors, from
of these products, like tobacco and alcohol, is known which we were able to conclude type, frequency, and du-
to produces a synergistic effect on carcinogenesis (5). ration of risk factors. The following products were grou-
Besides habits, rising infection with certain viruses, like ped under ‘smokeless tobacco’ category: gutka, mawa,
DNA viruses, Epstein Barr virus (EBV) and Human Pa- mainpuri, and naswar. The third part of questionnaire
pilloma virus (HPV) (especially HPV-16 and HPV-18) enabled exact characterization of patients’ oral condition
have also been reported to play a key role in OC patho- that helped us in determining early signs, if any, related
genesis (11). Importance of HPV in OC pathogenesis is to OC, for instance; ulcer, red patch, white patch, mixed
highlighted by the fact that the 2017 update of 4th edi- red-white patch, lump in the mouth or neck etc.
tion of World Health Organization (WHO) classification The data was analyzed using SPSS version 16. Univaria-
of head and neck tumors has recognized HPV-related te logistic regression was done followed by multivariate
SCC as a distinct entity (12). logistic regression for identifying the risk factors and ad-

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justing for the confounding variables. Mann-Whitney U The mean age of the respondents was 45 years with a
test was used for mean comparison between two study standard deviation of 11 years for cases (Range: 27 – 70
groups with the level of significance set as p<0.05. years) and 40 years with a standard deviation of 16 years
for controls (Range: 7 – 81 years). Majority of study par-
Results ticipants were in the age group between 31 and 40 years.
A total of 124 participants were enrolled in study, 50% Among the 62 cases, an overwhelming majority (71%)
cases (n=62) and 50% controls (n=62). The participants’ was recorded in buccal mucosa, making latter the most
demographics are summarized in Tables 1 and 2. susceptible site in our study population (Table 1).

Table 1: Demographic data of study participants: Age, gender, and site distribution
of cases and controls.
Variable Cases n (%) Controls n (%)

Gender
Male 49 (79) 48(77.4)
Female 13 (21) 14 (22.6)
Age Group
</= 30 7 (11.3) 19 (30.6)
31-50 34 (54.8) 28 (45.1)
51-70 21 (33.9) 12 (19.3)
>71 0 (0) 3 (4.8)
Site of oral cancer
Buccal Mucosa 44 (71) -
Tongue 2 (3.2) -
Floor of the mouth 2 (3.2) -
Palate 3 (4.8) -
Others 11 (17.7) -

Table 2: Statistical association with Age and Gender. A statistically signinficant difference exists between Cases
and Control in Age Group but not in Gender.
Significance of Age and Gender among participants

Group

Control Cases
P-value
Count Column Count Column

Valid N Valid N

Age Group <= 40 35 56.5 21 33.9 0.012*

>40 27 43.5 41 66.1

Gender Male 48 77.4 48 77.4 1

Female 14 22.6 14 22.6

*p<0.05 considered significant using Pearson Chi Square test.

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A significant difference was observed in smokeless to- no history of habitual use for any of the anticipated risk
bacco consumption between cases and controls, whereby factors (Table 3).
15% of study participants that reported habit of smokeless Using Odds ratio and Mann Whitney U test, we were
tobacco consumption, 63% were cases and 37% were able to conclude a significant association of smokeless
controls. A slightly greater difference was recorded when tobacco consumption with head and neck squamous cell
participants consumed smokeless tobacco with other ha- carcinoma incidence in our study population (Tables
bit(s) (14.5% of participants), with 72% recorded in cases 4,5).
compared with 28% in controls (Table 3).  
An interesting trend was noted in smokers, those par- Discussion
ticipants who smoked alone, without any other habit An 8 to 10-fold increase in oral cancer risk has been re-
(17% of the respondents) only 23.8% were cases and ported in Pakistan recently and consumption of tobac-
76.2% were controls. On the contrary, respondents who co-related products has been identified as the main cul-
used cigarette with other habit(s) (11.3%) encompassed prit for this surge(13). The present study was undertaken
92.8% cases and mere 7.2% of controls. Another inte- to appraise risk of oral cancer development in relation to
resting finding was that 11.3% of cases (n=7) reported use of these products.

Table 3: Distribution of habits among cases and controls. Among the cases, 42% of the patients consumed smokeless
tobacco alone and in combination with other products. 8% smoked cigarettes and 17.7% smoked cigarettes in combina-
tion with other products, 12.9% from cases presented without habits.
Habit Case n (%) Control n (%)

Smokeless tobacco 12 (63) 7 (37)

Smoking 5 (23.8) 16 (76.2)

Betel nut 3 (13) 20 (87)

Betel quid 4 (30.7) 9 (69.3)

Supari - 2 (100)

Betel nut with supari 2(100) -

Smoking with other habits 13 (92.8) 1 (7.2)

Smokeless tobacco with other habits 13 (72.2) 5 (27.8)

Betel nut with betel quid 2 (50) 2 (50)

Alcohol with smoking 1 (100) -

No habits 7 (50) 7 (50)

Table 4: Association of quantity of consumption with oral cancer using Odds RATIO Estimation using Logistic Regression. Significant
association recorded with smokeless tobacco (ST) consumption.
Odds RATIO Estimation using Logistic Regression

CONSUMPTION odds ratio 95 C.I

LOWER UPPER p-value

Betel Quid Consumption Quantity 1.170 1.012 1.352 .034*

Betel Nut Consumption Quantity 1.078 .970 1.197 0.163

Supari Consumption Quantity 1.111 .868 1.423 0.403

ST Consumption Quantity 1.179 1.048 1.325 0.006*

*P<0.05 considered significant.

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J Clin Exp Dent. 2018;10(4):e396-401. Risk factors for Oral Cancer

Table 5: Association of quantity of consumption with oral cancer using Mean Comparison of cases and controls. Significant as-
sociation recorded with smokeless tobacco (ST) consumption.

Mean comparison of cases and control

CONSUMPTION Group p-value

Control Cases

Mean Std. Deviation Mean Std. Deviation

Betel Quid Consumption 0.74 ±1.864 1.94 ± 3.666 .095

Quantity

Betel Nut Consumption 1.48 ±1.981 2.44 ± 4.82 .473

Quntity

Supari Consumption Quantity 0.19 ± 1.291 0.47 ± 2.07 .149

ST Consumption Quantity 1.1 ± 3.547 3.45 ± 4.79 .000*

P<0.05 considered significant using Mann Whitney U test.

Exposure to pertinent risk factors plays a key role in be clearly elucidated since some studies have indicated
determination of predominant tumour site in particular an inversely proportional relationship between tobacco
geographical region (14). Studies from India, Japan, consumption and HPV DNA detection in tumour spe-
Taiwan, Thailand, Yemen, and Iran have reported that cimens warranting further research to characterize the
tongue encompassed an estimated 42% of all oral cancer association, if any (19).
cases in these regions (14). Cancers involving labial mu- In present study both, the duration and frequency of con-
cosa predominate in Myanmar region (14). In Pakistan, sumption of studied habits are increased in oral cancer
however, oral cancer shows a strong predilection for in- patients. However, there is a greater emphasis on the
volvement of buccal mucosa in both genders, a finding effect that the period of consumption has on the patients.
consistent with present study (15). The most frequently The maximum period of consumption was more than 10
afflicted site is an indication for carcinogenic poten- years for cases and in controls it was 3 years. Consump-
tial of habits such as smokeless tobacco use. Various tion of smokeless tobacco combined with other products
smokeless tobacco products such as niswar and gutka produced a synergistic effect that appeared to increase
are placed chronically in the buccal sulcus by users, a the risk of cancer, consistent with previous report(13).
plausible explanation for observed association with buc- Betel nut was the most consumed risk factor probably
cal squamous cell carcinoma. because betel nut, also referred to as ‘chaalia’, is a very
Consistent with previously reported studies, we found cultural product. Children tend to have easy access to it
smokeless tobacco consumption to be a widely consu- at because unlike cigarette smoking, it is not considered
med and significant risk factor for oral squamous cell a taboo by Pakistani society and because it is extremely
carcinoma (16-18). Despite increasing awareness among inexpensive.
scientists of threat posed, tobacco-related products re-
main a popular health risk in Pakistan. Easy access to Conclusions
these carcinogenic substances by even school children This study establishes a strong evidence for smokeless
and their addiction potential as well as affordability are tobacco to be independent risk factor for oral cancer by
major hindrances to curb this vice from our society (13). showing significantly higher odds ratio of oral cancer
In smokeless tobacco products, nitrosamines have been development in these patients. Despite advancement in
recognized as most potent carcinogens with their me- our knowledge and understanding of carcinogenic po-
tabolites expressed in saliva and body fluids (19). A tential of these hazardous substances not enough efforts
combined carcinogenic effect of smokeless tobacco has have been put forth to effectively control their wides-
also been indicated with Herpes simplex virus 1 (HSV- pread sale and consumption, particularly by the youth
1), and high-risk HPV but this association remains to in our society.

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Conflicts of Interested
Authors have no conflicts of interest to declare.
This study did not receive any funding.

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