European Journal of Cardiovascular Medicine

The prevalence of oral cancer is high among the Southeast Asian countries due to the wide use of tobacco products, especially in the chewable form (1). In India alone, an estimated number of 1,35,929 cases were diagnosed with Lip & Oral cavity cancer (10.3%) in the year 2020 according to Globocan data with 72,290(8.8%) estimated deaths (2). In India, oral cancer is one of the commonest cancers in both sexes, accounting for 30% of the overall cancer burden, which is likely to increase in the future (3). Tobacco causes most oral cavity cancers, and alcohol synergistically increases the risk of these cancers conferred by tobacco use (4) However, the risk of alcohol consumption without tobacco use is unclear. In India, the habit of chewing pan (mixture of lime and tobacco in betel nut leaves) results in prolonged carcinogen exposure to the oral mucosa and is thought to be the leading cause of oral cancer (5). Surgery is the preferred modality of treatment with surgical extend being decided by disease factors. Single modality treatment is preferred for early stages and multimodality including concurrent and adjuvant radiation or systemic treatment for advanced stages (6). Despite the various treatment modalities available, the overall 5-year survival rate after treatment of oral cancer (all the stages included) is around 50%. Loco-regional recurrence is the most common cause for treatment failure. Recurrence is known to occur in about35% of patients treated for oral cancer (3). Survival data is the key outcome of treatment of OSCC, helps in formulation, surveillance and outcome analysis of health care programs and to determine factors affecting the outcome (7). Despite having the greatest number of Oral cancer cases in the world, a very scarce information is available about the survival of oral cancer patients. There exists a gap in literature to identify the factors associated with recurrence in patients treated for oral cancer, in varied Indian settings, where the occurrence of oral cancers is very high. This study is aimed about finding the 5-year survival of Oral cancer patients along with other factors associated with recurrence.

Study settings:

This was a record based retrospective study conducted by reviewing the patient’s clinical and treatment records in the Department of General surgery in a tertiary care centre of Central India.

Study population:

Our study included all patients who were diagnosed to have Oral Squamous Cell Carcinomas and treated by Surgery as the primary modality of treatment in the Department of General surgery between December 2017 and November 2018. Retrospective treatment records were collected from central registration and evaluated. The inclusion criteria were defined as histo-pathologically confirmed newly diagnosed cases of Oral Squamous Cell Carcinomas of the Oral cavity and treated with a curative intent. Patients with non-squamous histology, distant metastasis, prior history of treatment for oral cavity malignancies, and those with incomplete data were excluded from the study.

Data Collection:

Basic demographic data and clinical data were collected from the records. This data included age, detailed history of tobacco and alcohol use, co-morbidities, Site of the cancer with tumour and nodal staging. Records of Neck dissection, extracapsular invasion of Nodes, margin status, Dysplasia at margin, perineural infiltration and histology of the tumour were collected. Survival & Recurrence at 2 year & 5 years after the completion of treatment was also recorded. Confidentiality of clinical and treatment data was maintained.

Survival Outcomes:

The overall survival was calculated from the 1st date of treatment to the date of death or last known date of patient being alive. Disease-free survival was calculated as the difference between first data of treatment to the date of recurrence.

Statistical Analysis:

The data collected was entered into excel sheet and analysis carried out by Statistical package for Social Sciences (SPSS) for Windows. Mean and Standard deviation along with range were used to analyse and summarize continuous variables. Chi-square test was used for nominal and ordinal variables. Kaplan-Meier analysis was done for overall survival, survival by stage and site and factors affecting survival. Log rank test was used to assess the significance. p<0.05 was found to be significant.

Of the 50 Oral cancer patients treated by Department of Surgery at a tertiary care centre in Central India during the study period were included in our study.

Table 1 Demographic characteristics

Nearly half of the patients were 50 years or older with mean and standard deviation of 49.4 years and 15.6 years. The age of the patients range from 27 to 79 years. All the cases were males. 48 out of 50 cases (96%) were users of tobacco mainly in the smokeless form like Khaini, Gutka , Betel quid etc., The mean years of Tobacco use and its standard deviation were 22.6 years and 12.2 years respectively. The quantity of smokeless tobacco use was not studied. All patients were either regular or occasional users of Alcohol. The mean years of Alcohol use and its standard deviation were 24.6 years and 12.5 years respectively. The quantity and type of Alcohol were not studied. 7 out of 20 patients were comorbid, most common being Diabetes Mellitus, Hypertension or both.

Table 2 Clinical Presentation

The Site of the Oral cancer was Gingivo Buccal sulcus alone in majority of patients (62%) followed by Buccal Mucosa alone and Gingivo buccal sulcus with Buccal Mucosa in 8 patients each (16%). More than half of the patients(52%) had T4 as their tumour staging followed by T3 (40%). 32 out of 50 patients (64%) had N3 nodal staging followed by N2 (24%). Based on the clinical TNM staging, all 50 patients had advanced disease (Stage 3 & 4). Only 6 patients (12%) had stage 3 disease whereas 44 patients (88%) had either Stage IVa or Stage IVb disease.

Table 3 Treatment Details

Ipsilateral Neck Dissection done in all 50 patients whereas contralateral neck dissection was done in 34 patients (68%). Extracapsular invasion was present in 21 patients (42%). Margin status was positive with dysplasia in only 1 patient (2%). Perineural invasion was present in only 12 patients (24%).  Poorly differentiated squamous cell carcinoma was present in 21 patients (42%) followed by moderately differentiated squamous cell carcinoma in 19 patients (38%) in Histology.

Table 4 Recurrence & Overall Survival

25 out of 50 patients had recurrence of the Oral Squamous cell carcinoma. At the end of 2 years, 37 patients (74%) were alive whereas at the end of 5 years, only 13 patients (26%) were alive. The 2 year and 5-year mortality of Oral Squamous Cell carcinoma patients were 26% and 74% respectively. The 5-year survival rate is very less because all our patients had stage III and stage IV disease at the time of diagnosis.

Table 5 Recurrence & its associated factors

Table 5 shows the association of various factors with the recurrence of Oral Squamous Cell Carcinomas. Various parameters like Age category, Comorbidity, contralateral neck dissection, TNM staging, Extra capsular invasion, Dysplasia with positive margins, Perineural invasion and histology were compared with recurrence.  Extracapsular invasion, perineural invasion and Histology were found to be associated and p value is found to be significant for recurrence of oral squamous cell carcinomas.

Table 6 5-Year Survival & its associated factors

Table 6 shows the association of various factors with the 5- year survival rates of Oral Squamous Cell Carcinomas. Various parameters like Age category, Comorbidity, contralateral neck dissection, TNM staging, Extracapsular invasion, Dysplasia with positive margins, Perineural invasion and histology were compared with 5-year survival. Contralateral neck dissection, Staging, Extracapsular invasion of nodes and Histology were found to be associated with 5 year survival rate and p value was found to be significant.

Figure 1 shows that there is significance difference in 5 year survival rate of Oral Squamous Cell Carcinoma patients according to TNM staging. Log rank test was used and p value was found to be 0.014.

Figure 2 shows that there is significance difference in 5-year survival rate of Oral Squamous Cell Carcinoma patients with extracapsular invasion of nodes. Log rank test was used and p value was found to be 0.002.

Figure 3 shows that there is significance difference between 5-year survival rate of Oral Squamous Cell Carcinoma patients with Histology. Log rank test was used and p value was found to be 0.004.

The overall survival at 5 years was found to be 26%. The Disease-free survival at the 5 years was found to be 50%.

Oral cancer is a global health problem. The increasing burden of this cancer in our country is a cause of major concern because of high morbidity and poor quality of life. Although, oral cancer is historically believed to be a disease of people of older age groups, recent studies have observed cases as early as the third decade. This increased incidence in younger age group is likely due to exposure to tobacco and alcohol at  an early age (as early as 10 years as per history given by the patients), especially in the low socioeconomic strata.(5).Lack of knowledge and awareness, inadequate suboptimal primary care and health care and referral facilities, delayed referral and low financial support lead to presentation in locally advanced T stages, especially in rural India(8).Al these factors affect the Overall Survival and Disease Free survival of the patients. As majority of the presentations are in advanced stages, resection with free margins and adjuvant therapy remains the criterion standard treatment for OSCC. Despite the best treatment offered, chances of recurrences remain high (9).

Unlike other studies, all of our patients are Males with history of current or past Tobacco use in 95% patients along with Alcohol use. There is no observed effect of age on recurrence unlike other studies conducted by Bakshi et al (10), Gilroy et al(11) and Pytynia et al(12). Most frequent sub site in the present study has been Gingivobuccal sulcus followed by the buccal mucosa whereas in study conducted by Chang et al (13),it was the buccal mucosa .The 5 year survival rate is less when compared with other studies conducted by Thavarool et al(3) and  Deepa Nair et al. because all of our patients presented with Advanced stages (III & IV) unlike other studies which have patients in Stage 1 and Stage 2. This can be attributed to the lack of awareness, lack of affordable health‑care facilities, low socioeconomic status, and scarcity of trained workforce (14). The 5 year survival rate is higher in our study when compared with a study conducted by Iyer et al (15)., which was only 5-15%.)., The 5 year survival rates in our study is lower when compared with study conducted by Kim et al (19). And Lee et al (20). The recurrence can occur in ipsilateral neck, contralateral neck or in primary site in advanced stage tumours, and this is independent of the type of neck dissection done. This is similar to study done by Thavarool et al (3)., All of our patients were users of both Tobacco and alcohol. Alcohol consumption has been shown to act synergistically with tobacco in the increased risk of development of oral cancer resulting in advanced Oral cancers (18). This is similar to study done by Lohia et al (5)., Extracapsular invasion, Perineural invasion and Histology of the tumour were found to be significantly associated with recurrence in patients of Oral Squamous Cell Carcinoma. Factors like advanced stage and Perineural invasion affect 5-year survival rates which is similar to study conducted by Thavarool et al (3)., Tumour staging showed a significant impact on Overall survival and recurrence in our study, similar to study done by Bakshi et al (10). Our study did not have any early-stage Oral cancer patients and hence, overall survival and recurrence in them cannot be studied. Tumor stage and grade were very strongly related to the level of survival in the present study similar to study done by Lohia et al (5). Kaplan meier analysis of 5-year survival rates with Extracapsular invasion of Nodes, Staging and histology of the tumour showed significant difference (p<0.05).

The study has important policy implications. First, the results of the study highlight the importance of oral cancer screening for early detection at the primary health care (PHC) setting which may help in improving survival rates. Future studies are recommended to explore the feasibility of cancer screening at the PHC level. (24). Strategies, to improve general public awareness about early detection of oral cancers must be in place

Based on the presented retrospective review of patient records, it is to be emphasized that the advanced Oral cancer patients have 5-year survival rate of 26% only. Staging of the tumour, Extracapsular invasion of nodes and histology of the tumour affect the 5-year survival rate of the Oral cancer patients. Increased awareness about Oral cancers, its risk factors and Signs and symptoms can reduce its incidence. Early detection of Oral cancers in Stage 1and stage 2 can result in increased 5-year survival rates of the patients.

Limitations:

First and foremost, limitation of this study is smaller sample size. This data is from patients of a single tertiary care centre in Central India and hence could not be generalised. A majority of patients are in advanced stages and this study cannot comment on the factors responsible for recurrence in early cases of OSCC.

Implications:

All of the patients diagnosed with OSCC in this study are either users of Tobacco or alcohol or both. Screening for Oral cancers in High-risk groups will help us identify Oral Premalignant disorders and cancers in the early stages and future studies should recommend to explore the feasibility of cancer screening at the PHC Level.  Strategies to improve general public awareness about early detection of oral cancers must be in place.

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