Prevalence of Non-tobacco Associated Tongue Squamous Cell Carcinoma-Retrospective Study

Ushanthika T1, Herald J Sherlin*2, Sivakumar M3 1Saveetha dental college and hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, 600077, Tamil Nadu, India 2Department of Oral pathology, Saveetha dental college and hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, 600077, Tamil Nadu, India 3Department of Oral and Maxillofacial surgery, Saveetha dental college and hospital, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, Tamil Nadu, India


INTRODUCTION
Oral squamous cell carcinoma stands as the sixth most common cancer present in the world (Warnakulasuriya, 2009). Oral Squamous Cell Carcinoma (OSCC) is a major health problem worldwide, especially in the developing countries (Jayaraj et al., 2015c). In India, oral cancer is one of the most prevalent cancers and continues to be a signi icant general health issue. Oral Tongue Squamous cell carcinoma (OTSCC), the most commonly affected oral malignant growth sub-site, is related with a poor therapeutic result and outcome and survival despite aggressive multi modality management (Viveka et al., 2016).
The age adjusted incidence rate (AAR) for carcinoma tongue has expanded from 3.6 to 5.7 per 100,000 people over the over 25 years (Thangaraj et al., 2016). OTSCC has been accounted for to be among the main two most common subsites among the oral cavity cancers across numerous reports in India. The carcinoma of the tongue constitutes twenty percent to ifty percent of all instances of oral squamous cell carcinoma (OSCC) (Dantas et al., 2003), with the anterior two thirds and the lateral borders usually being the most affected areas.
Regardless of the way that the consolidated impacts of tobacco and alcohol consumption may expand the risk of developing carcinoma, there are etiologies that play a signi icant role in the development of carcinoma in patients without a background of drinking and smoking. Despite the fact that it's not totally clari ied, several factors have been known to cause human papilloma infection (HPV), diet and hereditary variables for this particular group (Sturgis et al., 2004).
Also other factors like oral epithelial dysplasia it's not uncommon for a mild dysplasia to rapidly progress to an invasive carcinoma like OSCC (Jayaraj et al., 2015a;Jangid et al., 2015). Also, other factors like oral epithelial dysplasia it's not uncommon for a mild dysplasia to rapidly progress to an invasive carcinoma like OSCC. Latest researches have exhibited that in patients not presented to smoking and drinking the lesions are prone to be classiied as well or moderately differentiated, while in people exposed to smoking and drinking, a lower level of cell differentiation has been observed (Kruse et al., 2010). As indicated by an investigation done in an oncology department in Chennai greater part of the OTSCC (85%) in patients without any habits are seen in advanced stages (Stages III and IV). Moreover early tongue cancers (Stages I and II) establish about 45% of all OTSCC's (Krishnamurthy and Ramshankar, 2013).
In oral cancer the role of saliva is used as a diagnostic tool in detecting Oral Squamous Cell Carcinoma (Shree et al., 2019). Investigation of salivary metabolomics may help in recognizing tumorspeci ic biomarkers for early diagnosis and forecast of tumor progression (Sridharan et al., 2019). Photography stands as one of the best ways to gather and save evidence of extra oral and intra oral pictures which helps in instructing, treatment and development (Hannah et al., 2018). Immunohistochemistry can be utilized for a better analysis and understanding (Sherlin et al., 2015;Swathy et al., 2015). A biopsy is done comparable to the histopathological changes in the oral mucosa among oral cancer patients utilizing hematoxylin and eosin and to the expression pattern of cytokeratin might be valuable in foreseeing epithelial separation in oral squamous cell carcinoma and mirror image biopsy (Gupta and Ramani, 2016).
There are many studies going on Syringic acid (SA) for its hepatoprotective, anti-in lammatory, free radical scavenging, and antioxidant activities. It is also said to have anti-carcinogenic properties and several studies have been going on to use it in OSCC and hepatocellular carcinoma (Gheena and Ezhilarasan, 2019). The early diagnosis and analysis of OSCC can lead to better prognosis and help in the execution of successful clinical treatment (Sridharan et al., 2017). However, surgery remains the best option for these patients unless proven otherwise (Jayaraj et al., 2015b). Most of the epidemiological studies have majorly focused on oral cancer as a whole, but however there are very few studies that have explicitly looked into OTSCC. The aim of the study was to assess the prevalence of non tobacco tongue OSCC and to correlate with the dental factors.

MATERIALS AND METHODS
It is a single centred retrospective study in a private dental institution. We took patients who were clinically diagnosed as non-tobacco tongue OSCC who checked in from June 2019 to March 2020.
Inclusion criteria -histopathologically con irmed cases of squamous cell carcinoma of tongue not associated with any habits are taken.
Exclusion criteria -patients with tobacco habits and patients with carcinoma other than OSCC Ethical clearance for this study was obtained from the institutional review board.
Data from 86000 patients visiting Saveetha dental college and Hospital were reviewed, and data was collected. The patients list was identi ied and the patients with non-tobacco tongue OSCC was taken and the case sheet was reviewed. It was crossveri ied by another examiner and using histopathology reports. Internal validity measures taken were Clinical, HP criteria, Habits and Control of confounders. The records of all patient data, biopsy details, histopathology, dental factors were taken.
The data was entered in the excel sheet and was imported to SPSS and the analysis was done using SPSS software version 19 by IBM. The Chi-square test was performed to compare the proportions between the parameters and p-value level of signi icance set at 0.05.

RESULTS AND DISCUSSION
As a result of our study we found 15 patients associated with non tobacco tongue OSCC. Out of which 60% of the patients were from age group 51 to 60 years. Hence, the most prevalent was in the age group 51 to 60 years of age among non tobacco tongue OSCC patients in Table 1.  The present study indings coincides with the study indings by Arvind (Krishnamurthy and Ramshankar, 2013) where the mean age reported was 53.4 years and majority of patients were in the age group of 51-70 years. This is in agreement with many other Indian studies show that the peak-age frequency of occurrence of oral cancers (including OTSCCs) in India is in the ifth decade, at least a           (Gupta et al., 2008;Iype et al., 2001).
Among the 15 patients 73.3% of them were males and 26.7 % of them were females. The males predilection was higher in non tobacco tongue OSCC patients in Table 2. The males predilection was higher in non-tobacco tongue OSCC patients in this study which correlated with (Krishnamurthy and Ramshankar, 2013). Where the male to female ratio was 3:1. Though the collective effects of tobacco and alcohol consumption may increase the risk of developing carcinoma yet, few factors such as HPV, diet, and genetic factors also play an important role in the development of carcinoma in patients without a history of drinking and smoking (Dahlstrom et al., 2008). HPV is the most common sexually transmitted infection. Many people are exposed to oral HPV in their life. About 10% of men and 3.6% of women have oral HPV, and oral HPV infection is more common with older age. Most people clear HPV within one to two years, but HPV infection persists in some people. The relationship between diet and nutrition to the risk of cancer development has been established by several epidemiological and laboratory studies (Jeng et al., 2001) Table 3.
The obtained results showed that most patients presented with pain, as shown in graph 3. The various locations seen among the 15 patients were 72% presented in the left and right lateral border of the tongue, 13.3 % of the patients presented in the ventral border of the tongue and 13.3 % posterior lateral border of the tongue. The most prevalent site was seen in the anterior lateral border of the tongue in Table 4. The present study indings correlated with Albuquerque et al study (Albuquerque et al., 2011) which states that the lateral borders of the tongue were the most frequent carcinoma locations in both habits and non-habit groups with 59.7% and 40.3% respectively. (Falaki et al., 2011) analyzed 158 cases of OSCC and found that the most common site of involvement was the tongue (66%) and lateral border of the tongue.
Out of 15 patients 73.3 % of the patients were not associated with any dental factors only 26.6 % of patients presented with Sharp cups in Table 5. In this study most patients were not associated with any dental factors. According to the study by (Chaturvedi et al., 2017) there is not enough available evidence which appears to be signi icant enough to support sharp teeth to be a risk factor in causing oral cancer. Many times, during the examination of oral cancer patients, we come across a sharp tooth at corresponding location on the alveolar arch. However, over review of literature, we could not ind any study which has separately looked at association between sharp tooth and oral cancer.
In the present study, we found that 80% of the patients presented with ulcerative lesions which correlated to other studies which found the same.
[ Table 6] According to (Wahi et al., 1965) most tumors of the oral cavity ulcerate, this could be due to the friction of the mucous membrane during eating.
In grading of OTSCC 66.7 % were WDSCC and 26.7% were MDSCC. The most commonly seen grading was WDSCC in patients with non tobacco tongue OSCC in Table 8. Considering the histological grading of tongue OSCC most patients in the present study had well differentiated squamous cell carcinoma (66%) followed by MDSCC (27%). Which correlated to (Selvamani et al., 2015) and Lawal et al (28) who found that well-differentiated OSCC accounted for 23 cases (44.2%), while moderately differentiated OSCC was seen in 29 cases (55.8%) and (Agarwal et al., 2011) found 10 cases (55.5%) of well-differentiated OSCC and 4 cases (22.2%) of moderately differentiated OSCC in his analysis. The phenotype of non-habit associated OSCC is generally well to moderately differentiated carcinoma. Comparative analysis of the expression of p53 inhabit and non-habit associated with OSCC show a signi icant decrease in expression in the latter. This could explain why the non-habit associated OTSCC patients with well differentiated squamous cell carcinoma shows a good response to radiotherapy and thus an improved overall prognosis (Rapidis et al., 1977).
The Staging of OTSCC observed in this study was stage III, which was found in 60% of the patients in Table 7. The most prevalent staging was stage III, which was 60% in this study which coincided with a similar inding by Karlo Mario Carvalho et al where most cases were seen was above stage III. Also relevant to the study by Arvind Krishnamurthy (Krishnamurthy and Ramshankar, 2013) majority of the oral cavity cancers (85%) in the cancer center was present in advanced stages (Stages III and IV), on the contrary early tongue cancers (Stages I and II) constitute nearly 45% of all OTSCCs. This shows the lack of awareness and reluctance for early medical attention in the population. The current recommendations to screen for oral cancer at every routine check-up is not practical and has not produced the intended results (Sivaramakrishnan and Ramani, 2015). Selective opportunistic screening may be a more realistic and effective solution. Detection of oral and oropharyngeal SCCs during a nonsymptom-driven examination has proved an association to lower stage at diagnosis, in the same way as patients with a regular primary care dentist are signi icantly more likely to be diagnosed at early stages Left lateral border of the tongue was the most common site of involvement in patients with no associated dental factors. There was no signi icance between dental factors and the site of Tongue SCC. Pearson Chi-square p=0.078 Figure 3 X-axis-denotes dental factors, Y-axis represents frequency. Blue denotes Stage I, Green denotes stage II, beige denotes Stage III, Purple denotes Stage IV. Most of the Tongue SCC patients were in Stage III and not associated with dental factors. There was no signi icance between dental factors and staging of Tongue SCC. Pearson Chi-square p=0.816 Figure 4 X-axis-denotes dental factors, Y-axis represents frequency of clinical appearance. Blue denotes ulcerated appearance, Green denotes erythematous presentation, Beige represents leukoplakia or white patch. There was no signi icant association between dental factors and clinical appearance of Tongue SCC. Pearson Chi-square p=0.626 The information obtained from the current study will help clinicians better understand the etiology and biology of OTSCC and can also potentially aid the policy makers to channelise the resources better for effective public health interventions. Limitation the study was done in a short duration. It was a short cross-sectional study of a particular population and other etiological factors were not assessed. The future scope of the study is based on a larger population and assessment of more etiological factors can be done. A long term study incorporating advanced pathological methods can give a better outcome. This information will help clinicians better understand the etiology and biology of OTSCC.

CONCLUSIONS
The present study highlights the clinical and histopathological characteristics of OTSCC which are not associated with habits. The study also emphasizes the need for identi ication of the proper etiological factors, which plays a pivotal role in prevention. Early detection and prevention of this particular type of oral cancer help in the institution of proper treatment, thereby improving the quality and quantity of life of the patients.