Abstract
The cumulative survival for all stages in oral squamous cell cancers (OSCC) in the world remains poor despite the advances in management; hence, we conducted this study to evaluate the survival outcomes. This is a retrospective review and analysis of treatment, follow-up and survival records of 249 OSCC patients treated in our department from April 2010 to April 2014. Telephonic interviews were conducted for survival details for some patients who had not reported. Survival analysis was done using the Kaplan-Meier analysis, comparisons were done using log-rank test and multivariate analysis was conducted using the Cox proportional hazard model to find different variables (site, age, sex, stage and treatment) affecting overall survival (OS)/disease-free survival (DFS). Two-year and 5-year DFS for OSCC were observed to be 72.3% and 58.3% with mean survival of 63.17 months (95% CI: 58.342–68.002). Similarly, OS at 2 years and 5 years were 84.3% and 55.9% with mean survival of 65.143 months (95% CI: 60.143–69.601). Tumour site, patient age, stage of disease and treatment modality had a statistically significant hazardous effect on the overall and disease-free survival rates. The significant influence of age, site of tumour, stage of disease and modality of treatment required based on the clinic-pathologic risk factors on prognosis emphasizes the importance of early diagnosis through regular screening and early treatment which can be ensured with early referral, high clinical suspicion and awareness at the point of primary/secondary care.
Keywords: Disease-free survival, Overall survival, Oral squamous cell cancers
Introduction
Oral cancer is the most common single site cancer in males and one among the most frequent sites (fifth in sequence) of cancer in females in Southeast Asia. 2018 reported 354,864 new cases of OSCC and 177,384 deaths worldwide (age-standardized rate of 2.8 per lakh population). [1] India has one-third of the global load of OSCC [2] and has contributed to 30% of global OSCC mortality (1,19,992 new cases and 72,616 deaths) in 2018 [3] having a difference in incidence between males (11.3%) and females (4.3%). Interestingly, Areca nut exposure affects the incidence in India by increasing the incidence in males and decreasing in females. [4] Squamous cancers predominate (90%) [5] and affect the overall prognosis.
Prolongation of survival along with maintenance for quality of life (QOL) is target treatment outcome for OSCC. [6] NCCN (National comprehensive cancer network) gives extensive guidelines for management. [7] 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. [8] Survival data is the key outcome of treatment of OSCC, helps in formulation, surveillance and outcome analysis of health care programs [9] and to determine factors affecting the outcome. [10] Hence, we conceptualized this retrospective analysis to evaluate the survival rates and various prognostic factors influencing the treatment outcome in OSCC patients presenting to our tertiary care centre.
Material and Methods
Study Settings
This record-based retrospective study was conducted by reviewing patients’ clinical and treatment records of department of Otolaryngology in our tertiary care hospital of North India.
Study Population
The study included all patients of OSCC treated and operated with primary surgical resection in a single surgical unit of ENT and Head and Neck Surgery department between 2010 and April 2014. Retrospective treatment records were collected from central registration and evaluated. The inclusion criteria were defined as histo-pathologically proven newly diagnosed cases of OSCC who were treated with a curative intent. Patients with non-squamous histology, distant metastasis and/or other site malignancy, and those who were previously treated for oral cavity malignancies, those treated with a palliative intent and those with incomplete data were excluded from the study.
Data Collection
Demographic and clinical data including age, sex, co-morbidities, addictions, primary tumour site, size, location and extent were noted. Oral cavity subsites were divided into buccal mucosa, tongue, alveolus, retro molar trigone and hard palate. Record of resection, neck dissection, complications and adjuvant treatments like radiotherapy and chemotherapy were collected along with the histopathological data of tumour size, depth, differentiation, periosteal and bony invasion, margins, lymph nodes and extra capsular invasion. Follow-up records regarding clinical status, residual and recurrence of disease, second primary and survival data were reviewed.
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 interval was calculated as the time difference between the first date of treatment to the date of recurrence.
Statistical Analysis
Confidentiality of clinical and treatment data was maintained. Analysis was carried out using Statistical Package for Social Sciences (SPSS) for Windows. Mean and standard deviation, median and range, proportion, relative risks, and 95% confidence intervals (CI) were used to summarize the analytic outputs. Kaplan-Meier analysis was done for overall survival, survival by stage and site and factors affecting survival. Cox proportional hazard models were used for multivariate analysis of significant univariate variables. p value < 0.05 was taken to be significant.
Results
Two hundred forty-nine patients operated between 2010 and April 2014 were included in the study as per the inclusion and exclusion criteria. Table 1 depicts the basic socio-demographic characteristics of these patients. Majority of the patients (52.2%) were in the age group of 45 to 60 years with mean age of 48.9 ± 12.31 years (between 18 to 81 years) among males (n = 206) and 53.86 ± 12.68 years (between 30 to 78 years) among females (n = 43). The patients were divided into age two groups, i.e. patients aged ≤ 45 years (n = 94, 37.8%) and > 45 years (n = 155, 62.2%). 68.7% (n = 171) patients were from rural areas and 42.6% (n = 106) patients had a positive history of using smokeless tobacco, whereas only 23.5% had a history of alcohol consumption. As an interesting observation, we noticed that there were many patients in the patient population in whom opium addiction was present with occasional smoked tobacco use in the absence of chewable tobacco use. The most common site involved was buccal mucosa (n = 106; 42.2%), followed by tongue (n = 82; 32.93%), alveolus (n = 44; 17.7%), hard palate (n = 9; 3.6%) and floor of mouth (n = 8; 3.2%). Combination of surgery and radiotherapy was the most common form of treatment. Out of 249 patients, at the completion of 5 years of follow-up, 126 (50.6%) patients did not show any evidence of disease after treatment, whereas 9 (3.6%) had recurrence and were alive. Ninety-two (36.94%) patients died, and the rest 22 (8.83%) were lost to follow-up. Of the 92 patients who died during the follow-up other than the lost to follow-up patients, only 2 cases had other causes of death which was cardiac arrest in one case and dyselectrolytemia due to chronic kidney disease in another. Most tumours were in the advanced stages of stage IV (n = 174; 69.9%) or III (n = 39, 15.7%). Two-year and 5-year disease-free survival of OSCC patients were observed to be 72.3% and 58.3% with mean of 63.17 months (95% CI: 58.342–68.002). Similarly, the overall survival for 2 years and 5 years was 84.3% and 55.9% with mean of 65.143 months (95% CI:60.143–69.601). Different sites of tumours were analysed for overall survival (Table 2) and disease-free survival (Table 3). Mean OS and DFS were highest for cancers originating from the alveolus (76.26 months (CI: 66.539–85.987) and 75.71 months (65.646–85.789)); followed by hard palate (71.87 months (66.146–77.604) and 70.00 months (62.742–77.258)), and buccal mucosa (59.14 months (52.68–65.614) and 57.94 months (50.886–64.994)) (Table 2). When the margins were analysed, six patients had positive microscopic margins (R1). All those cases were advanced-stage IV tumours. Four of them had prior neoadjuvant chemotherapy due to borderline operability. Of these 6 cases, only one case had anterior lip margin positivity, who was taken for revision surgery to excise the margin followed by adjuvant chemoradiotherapy (CRT). The rest of the 5 cases were given adjuvant CRT without any surgical margin revision as these were posterior and superior margins in patients who already had infratemporal and pterygoid space involvement and clearances were not possible. All these 6 cases constituted 13% of the patients (6/46) who received Sx and CRT. In terms of subgroup analysis among stage IV or those who received Sx and RT, these six patients did not differ significantly from other patients who received Sx and CRT in terms of survival.
Table 1.
Basic characteristics of the patients who were included in the study
| Variable | Number | Percentage |
|---|---|---|
| Total | 249 | 100 |
| Age group | ||
| ≤ 45 years | 94 | 37.8 |
| > 45 years | 155 | 62.2 |
| Gender | ||
| Male | 206 | 82.7 |
| Female | 43 | 17.3 |
| Residential status | ||
| Rural | 171 | 68.7 |
| Urban | 78 | 31.3 |
| History of substance abuse | ||
| Tobacco | 105 | 42.1 |
| Alcohol | 60 | 23.5 |
| Site of tumour | ||
| Alveolus | 44 | 17.7 |
| Buccal cavity | 106 | 42.6 |
| Floor of mouth | 8 | 3.2 |
| Hard palate | 9 | 3.6 |
| Tongue | 82 | 39.9 |
| Type of treatment given* | ||
| Only surgery | 21 | 8.4 |
| Sx + RT | 182 | 73.0 |
| Sx + RT + CCT | 46 | 18.5 |
*Sx, surgery; RT, radiotherapy; CCT, combination chemotherapy
Table 2.
Overall survival at 2 years and 5 years, respectively
| Mean overall survival time in months (95% CI) | 2-year survival | 5-year survival | |
|---|---|---|---|
| Age groups | |||
| ≤ 45 years (n = 94) | 69.26 (63.297–75.226) | 89.4% | 69.0% |
| > 45 years (n = 155) | 60.05 (54.276–65.829) | 80.5% | 47.7% |
| Site of tumour | |||
| Alveolus (n = 44) | 76.26 (66.539–85.987) | 86.1 | 75.9 |
| Buccal cavity (n = 106) | 59.14 (52.68–65.614) | 82.0 | 46.9 |
| Floor of mouth (n = 8) | 39.542 (22.993–56.091) | 62.5 | 41.7 |
| Hard palate (n = 9) | 71.87 (66.146–77.604) | 93.5 | 87.5 |
| Tongue (n = 82) | 54.35 (48.260–60.445) | 81.7 | 51.5 |
| Stage of tumour | |||
| I (n = 19) | 79.84 (71.424–88.270) | 94.7 | 80.0 |
| II (n = 17) | 77.84 (71.316–84.376) | 92.3 | 82.1 |
| III (n = 39) | 75.90 (70.359–81.442) | 86.7 | 84.7 |
| IV (n = 174) | 56.11 (50.522–61.713) | 75.7 | 43.7 |
| Type of treatment* | |||
| Only surgery (n = 21) | 67.03 (53.740–80.321) | 81.0 | 64.3 |
| Sx + RT (n = 182) | 71.07 (66.102–76.039) | 88.4 | 64.3 |
| Sx + RT + CCT (n = 46) | 34.64 (28.006–41.273) | 60.9 | 14.7 |
*Sx, surgery; RT, radiotherapy; CCT, chemotherapy
Table 3.
Disease-free survival at 2 years and 5 years, respectively
| Mean overall survival time in months (95% CI) | 2-year survival % | 5-year survival % | |
|---|---|---|---|
| Age groups | |||
| ≤ 45 years (n = 94) | 67.00 (60.254–73.746) | 78.3 | 72.1 |
| > 45 years (n = 155) | 58.05 (51.817–64.300) | 69.9 | 49.6 |
| Site of tumour | |||
| Alveolus (n = 44) | 75.71 (65.646–85.789) | 81.2 | 77.8 |
| Buccal cavity (n = 106) | 57.94 (50.886–64.994) | 72.5 | 51.4 |
| Floor of mouth (n = 8) | 36.78 (19.032–54.530) | 62.5 | 46.9 |
| Hard palate (n = 9) | 70.00 (62.742–77.258) | 85.7 | 63.4 |
| Tongue (n = 82) | 50.43 (43.400–57.473) | 63.9 | 53.1 |
| Stage of tumour | |||
| I (n = 19) | 79.53 (70.669–88.405) | 94.7 | 82.1 |
| II (n = 17) | 77.43 (70.320–84.555) | 93.8 | 83.3 |
| III (n = 39) | 76.01 (70.457–81.563) | 94.9 | 88.6 |
| IV (n = 174) | 53.37 (47.277–59.471) | 61.8 | 46.1 |
| Type of treatment* | |||
| Only surgery (n = 21) | 69.89 (50.441–79.347) | 76.2 | 64.5 |
| Sx + RT (n = 182) | 70.15 (64.913–75.398) | 80.5 | 66.4 |
| Sx + RT + CCT (n = 46) | 28.29 (20.081–36.516) | 35.5 | 21.6 |
*Sx, surgery; RT, radiotherapy; CCT, chemotherapy
Factors Influencing Survival
Factors found to be individually significant in single factorial analysis were included in the multi-variance analysis through Cox proportional hazard measure to see their combined effect on the overall survival and disease-free survival along with the calculation of the hazards to look for the mortality which was related to the disease. Age > 45 years was found to have a significant impact on the cumulative survival of the patients (Fig. 1). The OS at 2 and 5 years for patients aged < 45 years of age was 89.4% and 69.0%, which was 80.5% and 47.7% for patients with age > 45 years (Table 2). The disease-free survival rates at 2 and 5 years were 78.3% and 72.1% for patients aged < 45 years and 69.9% and 49.6% for patients aged > 45 years of age (Table 3). This was significant both for OS (p = 0.004, HR = 2.014 (1.246 to 3.256) Table 4) and DFS (p = 0.009, HR = 1.879 (1.167 to 3.025) Table 5). Similarly, the survival values were significantly lower for buccal mucosa and tongue cancer patients as per the values mentioned above which were significantly lesser than that for the hard palate and alveolus which can be seen in survival functions as per subsites in Fig. 2. Stage IV patients did perform significantly worse in terms of survival compared with stages I, II and III (Fig. 3, Tables 2 and 3) which was significant for both overall survival (p = 0.000, HR = 22.858, Table 4) and disease-free survival (p = 0.000, HR = 18.012). Patients who were given surgery (Sx) and adjuvant chemoradiotherapy (CRT) performed worse compared with those patients who were given Sx and adjvant radiotherapy (RT) as indicated (Fig. 4). This observation might be because of the fact that Sx and CRT were required in patients of late advanced disease which had clear risk factors of extranodal extension and presence of gross lymphovascular invasion, for which systemic therapy was added along with the standard dual therapy. Similarly, on studying the hazard functions at the mean of covariates for overall and disease-free survival, we could see that the cumulative hazard, the total probability/chance of a patient having the hazard which is death for OS and recurrence for DFS at the end of 5 years of follow-up, went around 0.5 for 60 months for overall survival and around 0.45 at 60 months for disease-free survival (Fig. 5) as was found with average 55.9% overall survival and 58.3% disease-free survival in our cases.
Fig. 1.
Survival functions of different age groups of the study participants
Table 4.
Cox proportional hazard measure for overall survival of the patients
| Variables | Log-rank p | Hazard ratio | 95.0% CI for Exp (B) | ||
|---|---|---|---|---|---|
| Lower | Upper | ||||
| Site | Alveolus | .006 | |||
| Buccal cavity | .005 | 2.954 | 1.398 | 6.243 | |
| Floor of mouth | .032 | 3.820 | 1.120 | 13.034 | |
| Hard palate | .490 | .481 | .060 | 3.844 | |
| tongue | .001 | 3.759 | 1.735 | 8.144 | |
| Age group | > 45 years | .004 | 2.014 | 1.246 | 3.256 |
| Sex | Sex | .244 | .720 | .414 | 1.251 |
| Stage of disease | I | .000 | |||
| II | .436 | 2.178 | .307 | 15.472 | |
| III | .216 | 2.952 | .532 | 16.391 | |
| IV | .000 | 22.858 | 5.065 | 103.150 | |
| Treatment given* | Only surgery | .000 | |||
| Sx + RT | .009 | .248 | .087 | .709 | |
| Sx + RT + CCT | .300 | .563 | .191 | 1.666 | |
*Sx, surgery; RT, radiotherapy; CCT, chemotherapy
Table 5.
Cox proportional hazard measure for disease-free survival of the patients
| Variables | Log-rank p | Hazard ratio | 95.0% CI for Exp(B) | ||
|---|---|---|---|---|---|
| Lower | Upper | ||||
| Site | Alveolus | .010 | |||
| Buccal cavity | .004 | 2.930 | 1.396 | 6.150 | |
| Floor of mouth | .028 | 3.918 | 1.158 | 13.257 | |
| Hard palate | .592 | .567 | .071 | 4.509 | |
| tongue | .001 | 3.542 | 1.648 | 7.616 | |
| Age group | > 45 years | .009 | 1.879 | 1.167 | 3.025 |
| Sex | Sex | .206 | .699 | .402 | 1.217 |
| Stage of disease | I | .000 | |||
| II | .506 | 1.945 | .274 | 13.811 | |
| III | .315 | 2.398 | .435 | 13.205 | |
| IV | .000 | 18.012 | 4.097 | 79.193 | |
| Treatment given* | Only surgery | .000 | |||
| Sx + RT | .014 | .271 | .096 | .764 | |
| Sx + RT + CCT | .446 | .659 | .225 | 1.927 | |
*Sx, surgery; RT, radiotherapy, CCT, chemotherapy
Fig. 2.
Survival functions of the study participants as per the location of the tumour
Fig. 3.
Survival functions of the study participants as per the stage of the tumour
Fig. 4.
Survival functions of the study participants as per the type of treatment given
Fig. 5.
Hazard function at the mean of covariates for overall survival and disease-free survival of the study participants
For advanced-stage tumours which need multimodality therapy, survival outcomes with modalities on a stage by stage grouping in terms of mean OS and DFS were calculated. In stage III, patients who were treated either surgery alone or surgery followed by adjuvant RT or surgery followed by adjuvant RT+ CT, there was no difference in terms of mean OS or DFS. However, among stage IV patients who constituted the significant bulk of our patient population, the patients who had only surgery and did not consent for radiotherapy after the primary surgical treatment had worst OS and DFS which was 13.87 and 7.5 months, respectively. However, all those who were treated with surgery followed by RT had an average of 42 months of overall survival and 38 months of disease-free survival. However, patients who required Sx and CRT among stage IV patients, average OS and DFS again worsened and were found out to be 29 months and 20 months, respectively. This change was statistically significant for both OS and DFS (Table 6).
Table 6.
Treatment outcomes in terms of mean OS and DFS with various modalities on a stage by stage grouping for advanced (stages III and IV) cancers
| N | Mean | Std. Deviation | |||
|---|---|---|---|---|---|
| Stage 3 | |||||
| DFS | Surgery | 1 | 59.000 | ||
| Surgery + RT | 37 | 49.676 | 19.5165 | ||
| Surgery + RT + CT | 1 | 51.000 | |||
| Total | 39 | 49.949 | 19.0553 | ||
| Model | Fixed effects | 19.5165 | |||
| Random effects | |||||
| p = 0.894 | |||||
| OS | Surgery | 1 | 59.000 | ||
| Surgery + RT | 37 | 51.081 | 18.2489 | ||
| Surgery + RT + CT | 1 | 51.000 | |||
| Total | 39 | 51.282 | 17.8074 | ||
| Model | Fixed effects | 18.2489 | |||
| Random effects | |||||
| p = 0.913 | |||||
| Stage 4 | |||||
| DFS | Surgery | 4 | 7.500 | 10.3763 | |
| Surgery + RT | 125 | 38.280 | 23.0272 | ||
| Surgery + RT + CT | 45 | 19.800 | 16.7136 | ||
| Total | 174 | 32.793 | 23.0962 | ||
| Model | Fixed effects | 21.4074 | |||
| Random effects | |||||
| p = 0.000 | |||||
| OS | Surgery | 4 | 13.875 | 13.5177 | |
| Surgery + RT | 125 | 42.068 | 20.8850 | ||
| Surgery + RT + CT | 45 | 29.378 | 15.1602 | ||
| Total | 174 | 38.138 | 20.4694 | ||
| Model | Fixed effects | 19.4587 | |||
| Random effects | |||||
| p = 0.000 | |||||
Discussion
OSCC constitutes the most common (~ 30%) head and neck cancer in India with an age-adjusted incidence rate of 20 per lakh population. [3, 11] 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 [12, 13] and these factors affect the overall survival and disease-free survival rates. Duration of hospital stay and time taken for recovery and high out of pocket expenditures also affect decision of the patients and the overall outcomes. 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. [14, 15]
In the present study, age had a significant effect on survival of patients with oral cancers with statistically significant higher hazard ratio for overall survival (2.0 times, p value < 0.05) as well as disease-free survival (1.8 times, p value < 0.05) in older age group as compared with the younger ones. These results are higher than those depicted by Chang TS et al. [16] The observed effect of age on prognosis is similar to few other cohort studies by Gilroy et al. and Pytynia et al., that depict a better survival rate in men especially in early stages and patients of < 50 years of age. [17, 18] On the contrary, some studies report a more aggressive course of disease in younger patients. [19, 20] Most frequent subsite in the present series has been buccal mucosa followed by the tongue, alveolus, hard palate and floor of the mouth, which was similar to few other studies in Indian and other Asian population such as those from Taiwan and Thailand. Strong association with betel quid and tobacco chewing habits in these regions explains similar trends. [16, 21–23] Sex distribution seen in the present study showing a male preponderance (n = 212) in OSCC in comparison with females (n = 37) is in agreement with other studies [16, 24, 25]. In contrast to Asian population, many western studies found gradually increasing incidences of oral and oropharyngeal SCC in young white females. [26, 27] This alteration of the gender distribution is likely due to the narrowing of the gap related to habits of smoking and drinking which has become socially acceptable among women in the western world. [28, 29] A significant gender difference in our cohort is coinciding with the current smoking trend according to Global Adult Tobacco Survey (GATS) [30] data, indicating a prevalence in smoking younger males (age group of 24–44 years) was many folds higher compared with the females. It is important to note that none of the female patients suffering from OSCC in the present study gave a positive history of tobacco consumption similar to the trends observed by Y Fan et al. [31] and is in contrast to the western literature.
Tumour stage showed a significant impact on overall survival and disease-free survival, apart from being more hazardous. Tumour stage was not identified as a prognostic factor in this study, which can be explained by the homogeneity of the study population in terms of the initial extent of the disease and presentation in advanced stages. The 5-year survival rate of persons with early-stage oral cancer according to the TNM staging system may reach 80–90% whereas for advanced-stage oral cancer, it is nearly 46%. In India, Iyer et al. reported 80% 5 years survival rates for buccal mucosa carcinoma in stage I and II disease [32] and it was as low as 5–15% for locally advanced disease stages III and IV. [33, 34]
Maximum benefit in terms of OS (71.07 months with 95% CI: 66.10–76.04) and DFS (70.15 months with 95% CI: 64.91–75.40) was seen in patients who had undergone surgical treatment and received postoperative radiotherapy after that along with maximum OS (88.4% and 64.3%) and DFS (80.5% and 66.4%) at the end of 2 years and 5 years. When all three modalities were used concomitantly in the same patient, it was least protective, with a minimum proportion of patients surviving 2 years and 5 years. This can be explained by the advanced histological stage in patients requiring chemotherapy along with surgery and RT. Andreadis C et al. observed no significant difference in overall survival with the help of chemotherapy as compared with surgery or radiation alone as modality of treatment. [35] Padma R et al. depicted that adding adjuvant chemotherapy with postoperative radiotherapy improves survival outcomes. [36] Pathologic positive margin has been proven to be an adverse prognostic factor for OSCC patients, which correlates with local recurrence and overall survival (OS). The 5-year OS in early-stage OSCC patients with safe margin, positive margin and close margin has been reported 78.2%, 61.4% and 50.8%, respectively, in literature. Surgical clear margins > 5 mm are recommended, to prevent local recurrence. Most authors believe that the most significant factor affecting the survival rate is tumour staging “by assessing the primary tumour size and cervical lymph node status”. Tumour characteristics particularly histologic parameters must be utilized along with staging characters to identify the prognosis and select favourable treatment.
Conclusion
Based on the presented retrospective review of patient records, it is to be emphasized that the rising incidence and the declining survival rates in north Indian population should be seen as alarming signal. In our study, a higher stage of the disease, increased age of the patient at presentation and presence of high-risk histologic features which required Sx and CRT showed to alter the survival grossly.
Implications
A significant population of the patient presenting in such an advanced stage to the institute raises concerns about the delayed presentation, which needs focus in terms of awareness, early referral and diagnosis for possible early treatment. Tobacco and smoking addiction were major contributing factors for high incidence of oral cancer in this region and emphasis should be given on health education and health promotion to encourage abstinence and de-addiction. Education should also aim towards self-examination to facilitate early diagnosis and intervention. Health care providers should also be sensitized and educated to diagnose and report early signs and symptoms of oral cancer. Hence, we feel that these survival figures can be improved with presentations of patients in lower stages, early in the course of the disease. High level of clinical suspicion at the primary place of presentation, early referral and control of addiction and habits can certainly help in improving these outcomes.
Limitations
The present retrospective review included patients of OSCC in our centre. Additional HPV analysis in all patients will help us understand the factors responsible for OSCC in the absence of tobacco use and other known risk factors. Minimization of lost to follow-up by careful and stringent follow-up to achieve complete or near complete data collection, inclusion of radiation details and greater sample size with larger sizes of the subgroup can validate our findings further and might help explore further variables which affect the survival of oral cancers in this part of the country.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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