|Year : 2016 | Volume
| Issue : 2 | Page : 33-36
Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study
Varsha Salian, Chethana Dinakar, Pushparaja Shetty, Vidya Ajila
Department of Oral Pathology and Microbiology, A B Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore, Karnataka, India
|Date of Submission||07-Dec-2015|
|Date of Acceptance||16-Mar-2016|
|Date of Web Publication||29-Apr-2016|
Dr. Varsha Salian
Department of Oral Pathology and Microbiology, A B Shetty Memorial Institute of Dental Sciences, Nitte University, Nityanand Nagar, Deralakatte, Mangalore 575018, Karnataka
Source of Support: None, Conflict of Interest: None
Aim: Oral squamous cell carcinomas (OSCCs) are among the most common cancers that affect human population worldwide. This study aims to analyze the epidemiology, risk factors, clinical and histopathological features, and metastasis in OSCC cases.
Methods: This retrospective cross-sectional study included the subjects reported to Department of Oral Pathology and Microbiology in A B Shetty Memorial Institute of Dental Sciences between 2009 and 2013. Data on age, gender, tumor location, lymph node metastasis, associated risk factors, and histopathological grades were recorded and subjected to Pearson's Chi-square analysis for any correlation between habits and other variables.
Results: A total of 61 cases were included. Male: female ratio was 2.6:1 with maximum cases seen in the fifth and sixth decades of life. Totally, 59 cases reported tobacco chewing habit and 2 cases reported sharp teeth. Quid chewing was the most frequently reported habit and buccal mucosa was the common site. Most cases were well differentiated, associated with quid chewing and without nodal metastasis. The correlation of habits to other variables was statistically insignificant (P < 0.05).
Conclusion: In this study, betel quid chewing was the most important etiological agent of OSCC and was associated with the few cases of poorly differentiated OSCC.
Keywords: Betel quid, oral squamous cell carcinoma, tobacco
|How to cite this article:|
Salian V, Dinakar C, Shetty P, Ajila V. Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study. Cancer Transl Med 2016;2:33-6
|How to cite this URL:|
Salian V, Dinakar C, Shetty P, Ajila V. Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study. Cancer Transl Med [serial online] 2016 [cited 2019 May 25];2:33-6. Available from: http://www.cancertm.com/text.asp?2016/2/2/33/181429
| Introduction|| |
Oral and oropharyngeal carcinomas are the sixth most common cancers worldwide and represent about 90% of all oral malignancies. , The incidence of oral squamous cell carcinomas (OSCCs) varies in different parts of the world and this difference is largely attributed to the exposure to risk factors specific to the area.  In Southeast Asia, oral cancer is the second most frequent form of cancer and the second most frequent cause of death from cancer among males. One-third of global cases and one-half of deaths from oral cancer are reported from Southeast Asia.  In India, oral cancer ranks the first among male and the third among female population which is related to the use of tobacco chewing in the form of betel quid, tobacco smoking, reverse smoking as well as other factors such as alcohol consumption, low socioeconomic status, poor hygiene, poor diet and viral infections, ill-fitting dentures, and chronic irritation from rough or fractured teeth.  Persons exposed to smoking, drinking, and betel quid chewing together are at high risk compared to individuals exposed to any one of these factors.  The male: female ratio is 2:1 and the average age of diagnosis is 57.1 years in males and 52.5 in females with highest prevalence in the sixth decade of life.  In Southeast Asia, most cases of OSCC occur in the buccal and commissural areas of the oral cavity. 
| Methods|| |
This retrospective cross-sectional study included 61 clinically diagnosed and histopathologically confirmed cases of OSCC from the Archives of the Department during the period of 2009-2013. Clinical data including age, gender, risk factors, presence of sharp tooth and appliances, tumor location, and histopathological grade with lymph node metastasis were recovered from patient archives.
Statistical analysis for the correlation between the variables, etiological factors of OSCC and age, gender, histopathological grade, and lymph node metastasis, was performed using Chi-square test.
| Results|| |
A total of 61 cases (44 males and 17 females) were included in this study with an age range of 28-77 years and a mean age of 57 years. The age distribution of patients is summarized in [Table 1]. Majority of the cases were distributed between 40 and 70 years; 26% in the age group of 41-50 years, 30% in the age group of 51-60, and 31% in the age group of 61-70 years. The most common etiological agent was quid chewing (54%) followed by smoking (15%). The combination of habits documented (and the percentage distribution of a number of cases) was quid chewing and alcohol (12%), smoking and quid chewing (8%), smoking and alcohol (5%), and smoking, quid chewing, and alcohol (3%). The sharp tooth as an etiological factor was found in 3% of the cases. The common site of occurrence of OSCC was the buccal mucosa (34%) followed by alveolus (26%), tongue (20%), palate (8%), maxilla and lip (5% each), and floor of the mouth (2%).
|Table 1: Age distribution, etiological factors, primary site, lymph node metastasis, and histopathological grade for 61 cases of oral squamous cell carcinoma |
Click here to view
The highest number of cases were well-differentiated squamous cell carcinoma (76%) followed by moderately differentiated (21%) and poorly differentiated (3%) [Figure 1]. Lymph node metastasis was seen in 20% of cases, majority of which were associated with the habit of quid chewing and 80% of the cases were not associated with any lymph node metastasis. There was no statistically significant correlation seen between etiological risk factors and any of the other variables including location, histopathological grade and lymph node metastasis. However, the poorly differentiated grade of OSCC was associated predominantly with betel quid chewing [Figure 1]. One of the two cases of poorly differentiated grade of OSCC aged < 30 years showed lymph node metastasis, whereas no recurrence was seen in both the cases. Histopathologically, one of the cases showed deeper invasion and muscle infiltration in the connective tissue, whereas none of them showed evidence of perineural invasion.
|Figure 1. The association between different histological grades of oral squamous cell carcinoma with etiological risk factors. Poorly differentiated oral squamous cell carcinoma was associated with betel quid chewing|
Click here to view
| Discussion|| |
Oral cavity cancer is the 8 th most frequent cancer in the world among males and 14 th among females with the major risk factors being tobacco and alcohol consumption.  The incidence of oral cancer differs in different regions of the world varying from over 20/100,000 in India to 10/100,000 in the USA, and < 2/100,000 in the Middle East.  In the United States, 3% of cancers occur in the oral cavity, whereas in India it is 30%. This difference may be due to regional variations as well as variations in the risk factors.  According to Murthy and Mathew,  cancers of the oral cavity are highest in Kerala in South India. Oral cancer in India is a major public health problem. Persons residing in rural areas may not have access to healthcare services. Due to this, diagnosis is delayed, treatment outcomes are poor, and cost of treatment is high.  International Agency for Research on Cancer mentions that cancers of the oral cavity, lungs, esophagus, stomach, cervix, and breast are commonly occurring cancers in the Indian population. 
A total of 61 cases were enrolled in this study which included 44 males and 17 females. Thus, the male: female ratio is 2.6:1 with male preponderance. This is in accordance with the study by Sharma et al., who found a male: female ratio of 2.2:1 in a North Indian population. However, in a study conducted in a rural population of Andhra Pradesh, it was observed that females were affected more than males, but this was attributed to the habit of reverse smoking which is more common in the female population of Andhra Pradesh.  Franceschi et al.  found that in Bengaluru, India, the oral cancer incidence rate was higher in females than males.
The age range of the patients in our study was between 28 and 77 years with a mean age of 57 years. This is in accordance with Shenoi et al. who reported that OSCC commonly occurs in the sixth decade of life. Oral cancers in younger individuals follow a more aggressive course and are associated with poor prognosis. ,, This was seen in our study as well as where a 28-year-old male patient with buccal mucosal cancer associated with quid chewing showed poorly differentiated OSCC and nodal metastasis.
The most common site of occurrence, in our study, was the buccal mucosa (34%) followed by alveolus (26%) and tongue (20%) which is the common site for oral cancers in countries where the use of quid chewing is common. This is probably because majority of the lesions correspond to the site of maximum exposure to betel quid and also to other related habits.  Shenoi et al. in their analysis also found buccal mucosa to be the most common site followed by the alveolus as in our study. Thus, our results were in accordance with previous findings. In Iran, the most common sites include the ventrolateral tongue and floor of the mouth.  Al-Rawi and Talabani  found that in their study in Iraq, the lip was the common site of oral cancer. In a study of subjects under the age of 35 years, suffering from oral cancer, the tongue was the most common site followed by buccal mucosa, especially in cases without habits of tobacco and alcohol. 
The most common risk factor found from our study was quid chewing accounting for 54% of cases. This is in accordance with most studies in Southeast Asian countries where betel quid and areca nut quid are chewed by the female and male population alike and also due to the widespread use of products such as gutkha and pan masala.  Currently, premixed areca nut, lime, and condiments with or without powdered tobacco are being marketed as gutkha and pan masala which is placed in the cheek and chewed or sucked for a variable amount of time.  Quid, which is known as pan, consists of betel leaf, areca nut, tobacco, and lime.  Quid chewing is proved to be an independent risk factor for oral cancer.  The combination of lime and tobacco causes an exothermic reaction which increases the susceptibility of oral mucosa to carcinogens. 
The second most common risk factor was found to be bidi/cigarette smoking alone (15%), which was higher than the number of cases showing a combination of smoking and chewing habits (8%) and smoking and alcohol consumption (5%). Krishna Rao et al. in their update on the epidemiology of oral cancer have mentioned that bidi smoking alone was at higher risk for oral cancer compared to its combination with quid chewing. Bidi smoking is common in South India than cigarette smoking. Bidi smokers have 3.1 times more risk of oral cancers compared to nonsmokers in South Asia which were seen in our study. 
The other combinations recorded were quid chewing and alcohol consumption (12%) and smoking, quid chewing, and alcohol consumption (3%). There were no cases reported with the history of alcohol consumption alone without other habits such as quid chewing or smoking which could be because alcohol consumption has a synergistic effect with quid chewing and smoking. Lin et al. stated that alcohol was not a significant independent risk factor; however, it increased 40 times when combined with quid chewing and smoking.
Petti et al.  stated that in multiexposed individuals, oral cancer risk was 50 times higher than in unexposed individuals. Franceschi et al. stated that increase in alcohol consumption leads to increased risk of oral and pharyngeal cancer even though the smoking level in a population remains nearly constant, which could be the reason why none of the cases in our study showed the habit of only alcohol consumption without other habits.
International head and neck cancer epidemiology and the alcohol-related cancers and genetic susceptibility in Europe studies reported that the smoking-drinking interaction was responsible for 40% of oral cancer cases.  The present study relatively showed a very small percentage of population falling into this category which could be because betel quid chewing was the most preferred way of tobacco consumption as compared to smoking and drinking.
The study conducted by Petti et al.  also reported that annually, 74.92% of oral cancer cases which occur in Southeast Asia are due to concurrent smoking, betel quid chewing, and alcohol consumption.  However, in our study, least number of subjects fell into this category. A possible explanation could be underreporting of habit history by patients.
The highest number of cases in our study were well-differentiated (76%) followed by moderately differentiated (21%) and poorly differentiated (3%). Lymph node metastasis was seen in 12 cases (20%). This is in accordance with previous literature which reports that the majority of OSCC patients present with well-differentiated carcinoma. ,, An interesting finding in our study was that the poorly differentiated grade of OSCC was mostly seen associated with betel quid chewing (66.7%). Betel quid is known to induce proliferation and differentiation of oral epithelial cells.  It has been associated with poorly differentiated tumors as well as tumors with increased invasive nature.  Src family kinases released from betel quid have been associated with cell migration and invasive potential of OSCC indicating a poor prognosis.  Fang et al. evaluated the association between histological differentiation of OSCC and clinicopathologic manifestations, adverse events after treatment, and outcomes of patients in a region prevalent for betel quid chewing. He found that poorly differentiated squamous cell carcinomas showed a higher probability of developing neck recurrence and distant metastasis, but not local recurrence or a second primary tumor. Poorly differentiated OSCC has been associated with greater incidence of cervical lymph node metastasis and recurrence.  In our study, one case of poorly differentiated OSCC showed nodal metastasis at presentation. Both cases showed no evidence of recurrence after treatment. Few studies have also linked lymphatic and vascular invasion with locoregional recurrence and distant metastasis.  Our cases showed no evidence of lymphatic or vascular invasion although muscle infiltration was seen in one case with poorly differentiated OSCC.
In conclusion, the present study has summarized cases of OSCC reporting to our institution. The etiological factor for OSCC in our study was betel quid chewing which is a common practice among both males and females in South India. The buccal mucosa was the common site of oral cancer as in most other Indian studies. Most OSCC in our study were well differentiated followed by moderately differentiated type which is similar to previously published reports. Among the few OSCC which was poorly differentiated, majority were associated with the habit of betel quid chewing.
I would like to acknowledge the postgraduates in the department, Dr. Shaloo Dahima and Dr. Manav Chaturvedi for extending their help and support in acquiring and tabulating data for the present study. I would also like to thank Dr. Srikant N for his help regarding statistical analysis for the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol
2009; 45 (4-5): 309-16.
Sharma P, Saxena S, Aggarwal P. Trends in the epidemiology of oral squamous cell carcinoma in Western UP: an institutional study. Indian J Dent Res
2010; 21 (3): 316-9.
Aruna DS, Prasad KV, Shavi GR, Ariga J, Rajesh G, Krishna M. Retrospective study on risk habits among oral cancer patients in Karnataka Cancer Therapy and Research Institute, Hubli, India. Asian Pac J Cancer Prev
2011; 12 (6): 1561-6.
Petti S, Masood M, Scully C. The magnitude of tobacco smoking-betel quid chewing-alcohol drinking interaction effect on oral cancer in South-East Asia. A meta-analysis of observational studies. PLoS One
2013; 8 (11): e78999.
Mathur PT, Dayal PK, Pai K. Correlation of clinical patterns of oral squamous cell carcinoma with age, site, sex and habits. J Indian Acad Oral Med Radiol
2011; 23 (2): 81-5.
Coelho KR. Challenges of the oral cancer burden in India. J Cancer Epidemiol
2012; 2012: 701932.
Murthy NS, Mathew A. Cancer epidemiology, prevention and control. Curr Sci
2004; 86 (4): 518-27.
Pindborg JJ, Mehta FS, Gupta PC, Daftary DK, Smith CJ. Reverse smoking in Andhra Pradesh, India: a study of palatal lesions among 10,169 villagers. Br J Cancer
1971; 25 (1): 10-20.
Franceschi S, Bidoli E, Herrero R, Muñoz N. Comparison of cancers of the oral cavity and pharynx worldwide: etiological clues. Oral Oncol
2000; 36 (1): 106-15.
Shenoi R, Devrukhkar V, Chaudhuri, Sharma BK, Sapre SB, Chikhale A. Demographic and clinical profile of oral squamous cell carcinoma patients: a retrospective study. Indian J Cancer
2012; 49 (1): 21-6.
Iype EM, Pandey M, Mathew A, Thomas G, Sebastian P, Nair MK. Oral cancer among patients under the age of 35 years. J Postgrad Med
2001; 47 (3): 171-6.
Mesquita JA, Cavalvanti AL, Nonaka CF, Godoy GP, Alves PM. Clinical and histopathological evidence of oral squamous cell carcinoma in young patients: systematized review. J Bras Patol Med Lab
2014; 50 (1): 67-74.
Falaki F, Dalirsani Z, Pakfetrat A, Falaki A, Saghravanian N, Nosratzehi T, Pazouki M. Clinical and histopathological analysis of oral squamous cell carcinoma of young patients in Mashhad, Iran: a retrospective study and review of literature. Med Oral Patol Oral Cir Bucal
2011; 16 (4): e473-7.
Al-Rawi NH, Talabani NG. Squamous cell carcinoma of the oral cavity: a case series analysis of clinical presentation and histological grading of 1,425 cases from Iraq. Clin Oral Investig
2008; 12 (1): 15-8.
Mack TM. The new pan-Asian paan problem. Lancet
2001; 357 (9269): 1638-9.
Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, Hayder SJ, Haider SM, Ikram M, Chuang SK, Saeed SA. Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer
2000; 86 (1): 128-31.
Krishna Rao SV, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade - An update (2000-2012). Asian Pac J Cancer Prev
2013; 14: 5567-77.
Rahman M, Sakamoto J, Fukui T. Bidi smoking and oral cancer: a meta-analysis. Int J Cancer
2003; 106 (4): 600-4.
Lin WJ, Jiang RS, Wu SH, Chen FJ, Liu SA. Smoking, alcohol, and betel quid and oral cancer: a prospective cohort study. J Oncol
2011; 2011: 525976.
Fang QG, Shi S, Li ZN, Zhang X, Liua FY, Xu ZF, Sun CF. Squamous cell carcinoma of the buccal mucosa: analysis of clinical presentation, outcome and prognostic factors. Mol Clin Oncol
2013; 1 (3): 531-4.
Fang KH, Kao HK, Cheng MH, Chang YL, Tsang NM, Huang YC, Lee LY, Yu JS, Hao SP, Chang KP. Histological differentiation of primary oral squamous cell carcinomas in an area of betel quid chewing prevalence. Otolaryngol Head Neck Surg
2009; 141 (6): 743-9.
Chen JY, Hung CC, Huang KL, Chen YT, Liu SY, Chiang WF, Chen HR, Yen CY, Wu YJ, Ko JY, Jou YS. Src family kinases mediate betel quid-induced oral cancer cell motility and could be a biomarker for early invasion in oral squamous cell carcinoma. Neoplasia
2008; 10 (12): 1393-401.
Muange P, Chindia M, Njiru W, Dimba E, Mutave R. Oral squamous cell carcinoma: a 6-month clinico-histopathologic audit in a Kenyan population. Open J Stomatol
2014; 4 (10): 475-83.
Adel M, Kao HK, Hsu CL, Huang JJ, Lee LY, Huang Y, Browne T, Tsang NM, Chang YL, Chang KP. Evaluation of lymphatic and vascular invasion in relation to clinicopathological factors and treatment outcome in oral cavity squamous cell carcinoma. Medicine (Baltimore)
2015; 94 (43): e1510.