|Year : 2017 | Volume
| Issue : 1 | Page : 29-34
Clinicopathological features of oral squamous cell carcinoma: A hospital-based retrospective study
T Smitha1, CV Mohan2, S Hemavathy3
1 Department of Oral Pathology, VS Dental College and Hospital, Bengaluru, Karnataka, India
2 Dental Care and Research Centre, Bengaluru, Karnataka, India
3 Department of Oral Pathology, Sri Rajiv Gandhi College of Dental Sciences, Bengaluru, Karnataka, India
|Date of Web Publication||20-Mar-2017|
Department of Oral Pathology, VS Dental College and Hospital, K.R. Road, V.V. Puram, Bengaluru - 560 004, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Oral squamous cell carcinoma (OSCC) is the most common neoplasm representing more than 80% of all oral cancer cases. Squamous cell carcinoma is defined as a “malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin and/or the presence of intercellular bridges.” Most epidemiological studies have revealed that heavy smoking and alcohol intake are the most important risk factors for oral cavity cancer. Occupational exposure to carcinogens, infections with certain papilloma viruses, and nutritional status are additional risk factors that have been associated with an increased cancer risk. Poor dental hygiene, accompanied by tooth loss, is another suspected risk factor.
Aim: The purpose of this study was to analyze the incidence and clinicopathological features of patients with OSCC along with information on age, sex, locality, habits, sites, and grade of lesion.
Methods: This was a retrospective studies (2007–2014) in which data on 301 oral squamous cell carcinoma were investigated. H&E-stained slides were reviewed by the two authors and classified according to the Broder's grading system. Demographic variables related to oral squamous cell carcinoma were analyzed along with the histopathological findings. Statistical analysis on patients' sample was performed using the MedCalc software (Ostend, Belgium) and visualizations were performed using Tableau Public 9.0 (Seattle, Washington).
Results: Significant associations between buccal mucosa (BM) as the tumor site and smokeless tobacco consumption, lip cancer tumor and beedi plus cigarette smoking, tumor of floor of the mouth and alcohol consumption, maxillary alveolus (MA) as the tumor site, and tobacco plus alcohol consumption were observed. Tumor of BM and gingivo-BM was more common in women, whereas tumor of floor of the mouth, hard palate, and MA sites was more common in men. Tumor involving the lip and gingivobuccal sites was more common in patients who were >60 years old, whereas the cancers of the tongue and hard palate sites were more common in patients whose age is <40 years. In our study cohort, well-differentiated tumors were predominantly present.
Conclusion: Dentists play a key role in the screening, detection, and treatment of oral cancers and they can educate public, more importantly the youth, to bring out changes in the attitude and awareness about oral cancers.
Keywords: Neoplasms, oral squamous cell carcinoma, role of dentists
|How to cite this article:|
Smitha T, Mohan C V, Hemavathy S. Clinicopathological features of oral squamous cell carcinoma: A hospital-based retrospective study. J NTR Univ Health Sci 2017;6:29-34
|How to cite this URL:|
Smitha T, Mohan C V, Hemavathy S. Clinicopathological features of oral squamous cell carcinoma: A hospital-based retrospective study. J NTR Univ Health Sci [serial online] 2017 [cited 2019 Nov 18];6:29-34. Available from: http://www.jdrntruhs.org/text.asp?2017/6/1/29/202587
| Introduction|| |
Oral squamous cell carcinoma (OSCC) is a result of a multistep process involving genetic mutations and chromosomal abnormalities.,
The common clinical feature of OSCC is an ulcerated lesion with a central necrotic area and rolled up margins., Common sites for OSCC are stratified squamous epithelial lining of the buccal mucosa (BM), tongue, floor of the mouth, palate, and lip.
Tobacco consumption in various forms including betel quid, tobacco with lime, beedi, and hookah is an important etiological factor for developing OSCC. Krishna et al. found that risk for developing OSCC is higher in individuals with a habit of tobacco chewing and smoking than those with chewing tobacco alone. Frequency and duration of alcohol and tobacco consumption have been found to play a role in oral cancer development. Subapriya et al. found that combination of tobacco use or smoking with alcohol consumption is a very potent risk factor for the development of OSCC in a population in South India. Ages of the individuals with OSCC vary according to the geographical location. Epidemiological data on OSCC from developed and developing countries have shown different patterns in the age distribution. In the developing countries, OSCC is mainly diagnosed in individuals aged more than 60 years,, whereas in developing countries, it is predominant in individuals between fourth and sixth decades of life., In an epidemiological study conducted in Canada, the mean age of the patients with OSCC was more than 60 years; and in the USA, oral cavity and oropharyngeal cancers combined according to the Surveillance, Epidemiology, and End Results Program reported a median age of 62.0 years at diagnosis. A study by Krishna et al. in the Indian subcontinent reported that approximately 75% of the patients with OSCC in a North Indian population were aged between 40 and 60 years. In another large study done by Singh et al., the mean age of the patients was 48 years; and in a study on a South Indian population by Nayak et al., the incidence of OSCC cases was prevalent in 40–45 and 60–65 years' age group.
In India, several studies have described the clinicopathological features of OSCC and highlighted specific sites in the oral cavity where the disease develops. Mehrotra et al. observed that the tongue is the commonly affected site in a sample of patients with oral cancer in Allahabad, Uttar Pradesh, India. A study conducted by Selvamani et al. in the southern part of India (Davangere, Karnataka) also found the tongue as the most affected site in OSCC cases. However, in other studies by Singh et al. and Shenoi et al., the alveolus was found to be the most commonly affected site. On the other hand, Krishna et al., Rai and Ahmed, and Sharma et al. found the BM as the predominantly involved site. In addition, studies were conducted by Singh et al. and Ranganathan et al. to verify whether there is any significant association between sex and age of patients with the different sites of development of OSCC. No differences were observed in terms of age or sex between the OSCC sites.
Early detection of neoplasms is necessary to reduce morbidity and mortality associated with oral cancers. Dentists play a major role in the early detection of oral cancers, thus increasing the survival rates of patients. An initiative was taken to screen the population from the rural districts of Bengaluru, Kolar and Ramnagar, and the diagnosed cases were referred to our teaching hospital for appropriate treatment modalities. The objectives of the article were to find out the age group with the highest number of OSCC, most commonly involved site, and prevalent grade of OSCC, as well as any association between the sites of cancer habits, sex, and age group of patients.
| Methods|| |
In a retrospective study (2007–2014), data of 301 OSCC biopsies received were obtained from laboratory records. After getting necessary approval of the Ethics Committee of the Institutional Review board, information provided on histopathology request forms from the department of oral pathology were collected. All specimens were fixed in 10% formalin, and then processed into paraffin-embedded sections and stained with hematoxylin and eosin. Special stains were occasionally employed. All the slides were reviewed by the authors and classified according to the Broder's grading system.
Statistical analysis on patients' sample was performed using the MedCalc for Windows, version 16.8.4 (MedCalc Software, Ostend, Belgium) and visualizations were performed using Tableau Public 9.0, Seattle, Washington. Information related to seven sites of origin of the tumors including BM, floor of the mouth, gingivobuccal (GB) sulcus, hard palate, maxillary alveolus (MA), tongue, and lip were considered. Six habits—alcohol consumption, beedi smoking, beedi plus cigarette smoking, smokeless tobacco use, tobacco plus alcohol consumption, and cigarette smoking––were considered for the analysis. People with no habits were also considered for analysis. Age of the patients was divided into three groups: <40 years, between 40 and 59 years, and 60 years or more.
| Results|| |
Statistical analysis showed that out of 301 patients with OSCC, most of the patients (33.9%) were aged 60 years or more followed by the patients aged between 40 and 59 years (37.2%). However, 28.9% of the patients were <40 years old.
The most common site for OSCC was the GB (38.21%), followed by BM (30.90%), tongue (12.29%), MA (8.64%), lip (3.99%), and floor of the mouth and hard palate (2.99%).
Our findings showed that 3.32% of the total patients had the habit of alcohol consumption while 8.31% had the habit of beedi smoking. Habit of beedi plus cigarette smoking was found in 3.99% of the patients, cigarette smoking in 0.33%, smokeless tobacco use in 40.86%, and habit of tobacco plus alcohol consumption was found in 21.93% of the patients. In our sample, 21.26% of the patients with OSCC had no tobacco or alcohol consumption habit. Smokeless tobacco consumption was the most prevalent habit among the patients with OSCC [Figure 1].
The association between the various sites of tumor and habits of patients with OSCC is shown in [Table 1]. Among the patients whose tumor initiated in the BM, 13 (13.98%) patients were beedi smokers, 5 (5.38%) patients had no habits, 72 (77.42%) patients used smokeless tobacco, and 3 patients were tobacco plus alcohol consumers (3.23%). Association between the BM site of tumor and habit of smokeless tobacco use was found to be highly statistically significant (P < 0.0001). The patients whose tumor initiated in the lip were beedi plus cigarette users (100%), and the association was highly statistically significant (P < 0.0001). However, most of the patients (97.30%) with tongue cancers had no habit of either tobacco or alcohol consumption. The association between the absence of any habit and tongue cancer was found to be highly statistically significant in our dataset (P < 0.0001). A total of nine patients (100%) with the habit of alcohol consumption developed OSCC in the floor of the mouth, and the association between them was highly statistically significant (P < 0.0001).
|TABLE 1: ASSOCIATION BETWEEN THE SITES OF TUMOR INITIATION AND HABITS OF PATIENTS|
Click here to view
Among the patients whose tumor site was the GB, 12 (10.43%) patients were beedi smokers, 1 (0.87%) was cigarette smoker, 14 (12.17%) patients were with no habits, 51 (44.35%) patients had the habit of smokeless tobacco consumption, and 37 (32.17%) patients had tobacco and alcohol consumption habit. Although the number of smokeless tobacco users was high in this group, association between GB tumor site and smokeless tobacco abuse was not found to be statistically significant (P = 0.33). Alcohol plus tobacco abusers were affected by OSCC in MA in our sample (100%). Association between MA sites and the habit of tobacco plus alcohol consumption was found to be statistically significant (P < 0.0001). Finally, nine (100%) patients having hard palate as the site of origin of OSCC had no associated habits and their association was found to be statistically significant (P < 0.0001).
The association between various sites of tumor and gender of patients with OSCC is reported in [Table 2]. Among the patients with tumor of the BM, 68 were women and 25 were men. Association between female sex and BM tumor site was found to be statistically significant (P < 0.0001). Among the patients with tumor of the tongue, 17 were women and 20 were men. Association between male sex and tongue as the tumor site was not statistically significant (P = 0.70). Only 12 men were found with lip as the tumor site, and the association between male sex and lip site was found to be statistically significant (P = 0.0006). Similar to lip cancer group, 26 men were observed with MA cancer. Association between male sex and MA sites was found to be statistically significant (P < 0.0001). In patients with the GB as the cancer site, 62 were women and 53 were men. Although the number of women were more in this group, association between female sex and GB sites was not statistically significant (P = 0.16). Among patients with OSCC having hard palate as the tumor site, nine patients were men and the association between male sex and hard palate site was found to be statistically significant (P = 0.003). Similar to patients with OSCC having hard palate as the origin of tumor initiation, nine men had floor of the mouth as the site of tumor initiation and the association between male sex and floor of the mouth as tumor initiation site was found to be statistically significant (P = 0.003).
|TABLE 2: ASSOCIATION BETWEEN THE SITES OF TUMOR INITIATION AND GENDER OF PATIENTS|
Click here to view
The association between various tumor sites and different age groups of patients with OSCC is reported in [Table 3]. Among the age groups considered, the BM as the tumor site was most prevalent in the age group of ≥40–<60 years (46 patients), and there was a statistically significant association between the age group of ≥ 40–<60 years and BM sites (P = 0.0033). Tongue (n = 30) was the most common site of tumor in the age group of <40 years, and there was a statistically significant association between them (P < 0.0001). Tumor of the lip was most commonly observed in the age group of >60 years (n = 12), and there is a statistically significant association between them (P < 0.0001). MA cancer was mostly found in the age group of patients aged between ≥40 and <60 years (n = 12). However, there was no statistically significant association between MA as the tumor site and the age group (P = 0.32). Among the age groups considered, GB as the tumor site was most prevalent in the age group of patients aged >60 years (n = 60). A statistically significant association between GB as the tumor site and the age group (P < 0.0001) was also observed. Cases of the hard palate as the tumor site were most prevalent in the age group of <40 years (n = 9) and floor of the mouth as the tumor site was most prevalent in the age group of ≥40–<60 years (n = 9). Both the sites were statistically significantly associated with the respective age groups (P ≤ 0.0001).
Among the samples analyzed for histopathological grading, well-differentiated tumor was the most prevalent type present in our sample. A total of 137 cases of well-differentiated tumor were observed. The numbers of poorly and moderately differentiated tumor cases were 25 and 135, respectively. Presence of all the three grades (poorly differentiated, moderately differentiated, and well differentiated) was observed in all the sites of tumor origin considered in our analysis [Figure 2]a,[Figure 2]b,[Figure 2]c.
|Figure 2: (a) Poorly differentiated tumors present in all the tumor sites. (b) Presence of well-differentiated tumors among all the considered sites. (c) Presence of moderately differentiated tumors among all the considered sites|
Click here to view
| Discussion|| |
We performed a comprehensive demographic analysis of 301 patients suffering from OSCC. Although our result showed that age group of patients between 40 and 59 years was the most affected group, we observed age group-specific distribution of oral cancer sites in our data sample. In synchronization with our study, a 25-year review by Sarkaria and Harari  identified 14 reports with three or more patients younger than 40 years of age with OSCC of the tongue. In the study of tongue cancer on Indian population by Selvamani et al., 12% of the patients were between the age group of 31–40 years. The result of our age group analysis on lip cancer is also consistent with the retrospective study conducted in Spain by Domínguez-Gordillo  who reported the mean age of the patients with lip cancer as 69.7 years (P < 0.05). However, our result on the age group prevalence of GB sulcus is not consistent with the study conducted by India Project Team of the International Cancer Genome Consortium, which indicated the presence of 50% of OSCC-GB cases in the 40–50 years' age group. Our analysis revealed that in our sample, GB tumor was the most prevalent subgroup. Although smokeless tobacco abusers were high in number in this subgroup, the association was not statistically significant. In our data, we observed that GB tumors were associated with both smokeless tobacco habit and tobacco plus alcohol habit, which is in accordance with the report of India Project Team of the International Cancer Genome Consortium. In our study, the second most prevalent subgroup of OSCC was BM, and the statistically significant habit associated with the site was smokeless tobacco chewing. Our results are similar to the findings of Krishna et al. who reported smokeless tobacco chewing as the most prevalent habit and BM as the most prevalent site of tumor among patients with OSCC in their sample. One of the striking findings from our retrospective analysis is that 97.30% of the patients with tongue cancers had no habit of either tobacco or alcohol consumption. This finding is in accordance with the findings by Krishnamurthy and Ramshankar  who reported that out of 458 tongue cancer cases, 86.4% were never alcohol users and 49.3% were never tobacco users.
Male-to-female ratio of the occurrence of OSCC is generally more than 1 as men are more affected by the disease compared to women. The ratio is 1.45 in Japanese, 1.5 in Pakistani, 1.65 in Yemeni, and 10.5 in Taiwanese patients. It may be noted that a reverse trend has been observed in Thailand  (male: female is 1:1.56). Results of our gender analysis of patients with OSCC revealed that the female sex is significantly associated with squamous cell cancers of BM, which was the predominant site among smokeless tobacco users. This finding is similar to the results obtained by Singh et al. who reported that smokeless form of tobacco was significantly associated in OSCC in women.
In the current study, a large number of OSCC cases were showing well-differentiated carcinoma. In this context, it may be mentioned that use of several biomarkers is being investigated to differentiate between poorly and well-differentiated tumors. Juneja et al. and Cuevas et al. have recently reported the expression of several tumor-associated genes such as p16, p53, and Bcl-2 in poor and well-differentiated OSCC.
| Summary and Conclusion|| |
In the current demographic analysis, we focused on age, sex, tumor initiation sites, and grading of patients with OSCC from a hospital in Bengaluru. The addictive habits associated with OSCC vary from one region to another and from one country to another. Therefore, the sites involved in tumor initiation also are different across different regions and countries.
Dentists are in a strong position and play a pivotal role. With the tremendous support from the institution backed by the management, many screening camps were conducted to screen and treat the oral cancer patients at our referral hospital from rural areas surrounding Bengaluru. Oral cancer fatalism in people is either due to not accepting professional advice on avenues for prevention or arriving too late for the therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jayasooriya PR, Pitakotuwage TN, Mendis BR, Lombardi T. Descriptive study of 896 oral squamous cell carcinomas from the only university based Oral Pathology Diagnostic Service in Sri Lanka. BMC Oral Health 2016;16:1.
Abrahao AC, Bonelli BV, Nunes FD, Dias EP, Cabral MG. Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders. Braz Oral Res 2011;25:34-41.
Pires FR, Ramos AB, Oliveira JB, Tavares AS, Luz PS, Santos TC. Oral squamous cell carcinoma: Clinicopathological features from 346 cases from a single oral pathology service during an 8-year period. J Appl Oral Sci 2013;21:460-7.
Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin 2002;52:195-215.
Singh MP, Kumar V, Agarwal A, Kumar R, Bhatt ML, Misra S. Clinico-epidemiological study of oral squamous cell carcinoma: A tertiary care centre study in North India. J Oral Biol Craniofac Res 2016;6:31-4.
Krishna A, Singh RK, Singh S, Verma P, Pal US, Tiwari S. Demographic risk factors, affected anatomical sites and clinicopathological profile for oral squamous cell carcinoma in a North Indian population. Asian Pac J Cancer Prev 2014;15:6755-60.
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.
Subapriya R, Thangavelu A, Mathavan B, Ramachandran CR, Nagini S. Assessment of risk factors for oral squamous cell carcinoma in Chidambaram, Southern India: A case-control study. Eur J Cancer Prev 2007;16:251-6.
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;49:21-6.
] [Full text]
Muir C, Weiland L. Upper aerodigestive tract cancers. Cancer 1995;75 1 Suppl: 147-53.
Sankaranarayanan R. Oral cancer in India: An epidemiologic and clinical review. Oral Surg Oral Med Oral Pathol 1990;69:325-30.
Erickson B, Biron VL, Zhang H, Seikaly H, Côté DW. Survival outcomes of First Nations patients with oral cavity squamous cell carcinoma (Poliquin 2014). J Otolaryngol Head Neck Surg 2015;44:4.
Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma – An update. CA Cancer J Clin 2015;65:401-21.
Nayak VN, Donoghue M, Selvamani M. Oral squamous cell carcinoma: A 5 years institutional study. J Med Radiol Pathol Surg 2015;1:3.
Mehrotra R, Pandya S, Chaudhary AK, Kumar M, Singh M. Prevalence of oral pre-malignant and malignant lesions at a tertiary level hospital in Allahabad, India. Asian Pac J Cancer Prev 2008;9:263-5.
Selvamani M, Yamunadevi A, Basandi PS, Madhushankari GS. Prevalence of oral squamous cell carcinoma of tongue in and around Davangere, Karnataka, India: A retrospective study over 13 years. J Pharm Bioallied Sci 2015;7 Suppl 2:S491-4.
Rai HC, Ahmed J. Clinicopathological correlation study of oral squamous cell carcinoma in a local Indian population. Asian Pac J Cancer Prev 2016;17:1251-4.
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;21:316-9.
] [Full text]
Ranganathan K, Rooban T, Rao UM. Oral squamous cell carcinoma in patients with and without predisposing habits in glossal and extra-glossal site: An institutional experience in South India. Indian J Cancer 2015;52:625-7.
] [Full text]
Sarkaria JN, Harari PM. Oral tongue cancer in young adults less than 40 years of age: Rationale for aggressive therapy. Head Neck 1994;16:107-11.
Domínguez-Gordillo A, Esparza-Gómez G, García-Jiménez B, Cerero-Lapiedra R, Casado-Gómez I, Romero-Lastra P, et al.
The pattern of lip cancer occurrence over the 1990-2011 period in public hospitals in Madrid, Spain. J Oral Pathol Med 2016;45:202-10.
India Project Team of the International Cancer Genome Consortium. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun 2013;4:2873.
Krishnamurthy A, Ramshankar V. Early stage oral tongue cancer among non-tobacco users – An increasing trend observed in a South Indian patient population presenting at a single centre. Asian Pac J Cancer Prev 2013;14:5061-5.
Ariyoshi Y, Shimahara M, Omura K, Yamamoto E, Mizuki H, Chiba H, et al.
Epidemiological study of malignant tumors in the oral and maxillofacial region: Survey of member institutions of the Japanese Society of Oral and Maxillofacial Surgeons, 2002. Int J Clin Oncol 2008;13:220-8.
Bhurgri Y, Bhurgri A, Usman A, Pervez S, Kayani N, Bashir I, et al.
Epidemiological review of head and neck cancers in Karachi. Asian Pac J Cancer Prev 2006;7:195-200.
Halboub ES, Al-Anazi YM, Al-Mohaya MA. Characterization of Yemeni patients treated for oral and pharyngeal cancers in Saudi Arabia. Saudi Med J 2011;32:1177-82.
Chiang CT, Hwang YH, Su CC, Tsai KY, Lian IeB, Yuan TH, et al.
Elucidating the underlying causes of oral cancer through spatial clustering in high-risk areas of Taiwan with a distinct gender ratio of incidence. Geospat Health 2010;4:230-42.
Kruaysawat W, Aekplakorn W, Chapman RS. Survival time and prognostic factors of oral cancer in Ubon Ratchathani Cancer Center. J Med Assoc Thai 2010;93:278-84.
Juneja S, Chaitanya NB, Agarwal M. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma. Indian J Cancer 2015;52:505-10.
] [Full text]
Cuevas Gonzalez JC, Gaitan Cepeda LA, Borges Yanez SA, Cornejo AD, Mori Estevez AD, Huerta ER. p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: A study of 208 cases. Indian J Pathol Microbiol 2016;59:153-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]