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Aim of the Study: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes., Methods: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS)., Results: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%., Conclusion: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed., Methods: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months., Results: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP., Conclusion: India needs to implement tailored strategies to reduce the economic burden from premature mortality., (© 2024 Wiley Periodicals LLC.)

Background: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF., Methods: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events., Results: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001)., Conclusion: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Tata Memorial Center Research Administration Council funded this study. The funding agency had no role in the design, conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Advanced head and neck cancers are known to cause swallowing dysfunction due to anatomical and post-treatment changes. Literature is sparse on post-surgical and/or multi-modality therapy-associated swallowing function in advanced oral cancers. We conducted this study to longitudinally assess and compare the pre- and post-therapy swallowing dysfunction associated with locally advanced oral cancers., Methods and Material: A prospective observational longitudinal study was conducted at a tertiary cancer center from 2017 to 2018 including treatment-naive cT4a oral cancer patients (AJCC 7th edition). The assessment was done pre-surgery, post-surgery, and post-adjuvant setting as per the scales (Dysphagia score, Penetration aspiration scale, and Yale pharyngeal residue (vallecular and pyriform fossa)., Results: Of the 30 patients in the study, 47.4%, 47.4%, 52.6%, and 47.4% experienced deterioration of Dysphagia score, Penetration-Aspiration Scale (PAS), vallecula residue, and pyriform residue scores in the postoperative period. And 52.6%, 47.4%, 68.4%, and 57.9% had inferior dysphagia score, PAS, vallecula, and pyriform residue scores even 6 months after completion of adjuvant therapy. The dysphagia score correlated well with other objective assessment scores at different time points., Conclusion: Swallowing functions are significantly affected by surgery and adjuvant therapy and continue to be affected even 6 months after completion of treatment. Appropriate rehabilitation and intervention must be offered to patients to reduce this problem. Dysphagia scores can predict the swallowing status similar to other objective assessments., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Background: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1., Methods: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression., Results: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells., Conclusion: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT)., Methods: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed., Results: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort., Conclusions: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT., (© 2023 Wiley Periodicals LLC.)

Background: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology., Patients and Methods: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC)., Results: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60)., Conclusions: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification., Clinical Trial Registration: NCT00193843., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Context: The submandibular glands (SMGs) excision during head-and-neck oncosurgeries lead to significant morbidity and degradation of quality of life (QOL). The preservation of SMGs during head-and-neck oncosurgeries, without affecting oncological safety, will improve QOL by preventing xerostomia in these patients., Aims: The aim of this retrospective study was to assess the involvement of SMG by malignancy during neck dissection being done for the squamous cell carcinoma (SCC) of tongue and to evaluate oncological safety of SMG preservation in SCC of the tongue. Settings and Design: The study design was a retrospective analytical study., Subjects and Methods: The study included 391 patients of SCC of tongue operated at Quaternary oncological center from January 2016 to February 2020. The treatment records of 371 patients were reviewed for demographical data, nodal metastasis, and histopathological involvement of SMG by SCC. The statistical analysis was done using SPSS 22., Results: A total of 555 necks dissected were assessed, out of which 95 necks dissected were positive for nodal metastasis at level Ib. The SMG was involved by SCC in only two cases, both of which were poorly differentiated SCC. No intraglandular lymph nodes were detected in any of the SMG dissected., Conclusions: The study showed that involvement of the SMG by SCC of the tongue is not very common, and it may be possible to preserve the SMG during neck dissection in selected cases in SCC of the tongue. The preservation will definitely improve QOL of the patients, as excision of the SMG is one of the prominent factors, resulting in xerostomia., Competing Interests: None

Purpose: The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment., Methods: This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity., Results: Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival ( P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival ( P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA., Conclusion: NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial., Competing Interests: Kumar PrabashResearch Funding: Biocon (Inst), Dr Reddy's Laboratories (Inst), Fresenius Kabi (Inst), Alkem Laboratories (Inst), NATCO Pharma (Inst), BDR Pharmaceutics (Inst), Roche (Inst) Vanita NoronhaResearch Funding: Amgen (Inst), Sanofi/Aventis (Inst), Dr Reddy's Laboratories (Inst), Intas (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: American Society of Clinical Oncology Anil D'CruzEmployment: Apollo Hospitals India, Bombay Hospitals MumbaiHonoraria: Biocon Pharma, Merck Serono, MSD OncologyNo other potential conflicts of interest were reported.

Purpose: Management of clinically node-negative (N0) neck in early-stage (T1-T2) oral and/or oropharyngeal squamous cell carcinoma (OOSCC) has been controversial. The purpose of this systematic review and meta-analysis was to compare sentinel lymph node biopsy (SLNB) with elective neck dissection (END) in early-stage OOSCC., Methods: Studies comparing SLNB versus END in early-stage clinically node-negative OOSCC were identified using validated search strategy. To be considered eligible, trials had to include patients with early-stage, clinically node-negative OOSCC who had been randomly assigned to either SLNB or END. Primary outcome of interest was overall survival (OS), while secondary outcomes included isolated neck nodal recurrence (NNR), loco-regional recurrence (LRR), and neck-shoulder function. Outcome data was pooled using random-effects model and reported as hazard ratio (HR) or risk ratio (RR) with 95% confidence interval (CI). Any p-value < 0.05 was considered statistically significant., Results: A total of 608 patients from three trials comparing SLNB versus END in early-stage clinically node-negative OOSCC were included. The pooled HR of death for SLNB versus END was 1.18 (95% CI: 0.79-1.78, p = 0.41) which was not statistically significant. The rates of isolated NNR (pooled RR = 1.11, 95% CI: 0.69-1.80, p = 0.66) and LRR (pooled RR = 1.18, 95% CI: 0.81-1.72, p = 0.39) were also similar. Pooled analysis of the neck-shoulder function significantly favoured SLNB arm (pooled RR = 1.21, 95% CI: 1.12-1.32, p < 0.00001)., Conclusion: There is low-certainty evidence that SLNB is oncologically non-inferior to END and is associated with potentially lesser functional morbidity making it an emerging alternative standard of care in patients with early-stage clinically node-negative OOSCC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the present study, the potential of Raman spectroscopy (RS) in predicting disease-free survival (DFS) in oral cancer patients has been explored. Raman spectra were obtained from the tumor and contralateral regions of 94 oral squamous cell carcinoma patients. These patients were managed surgically and recommended for adjuvant therapy. The Cox proportional survival analysis was carried out to identify the spectral regions that can be correlated to DFS. The survival analysis was performed with 95% confidence intervals, hazard ratio, and p-values in the 1200-1800 cm -1 spectral region. Out of a total of 182 spectral points, 76 were found to be correlating with DFS, suggesting their utility to predict the patient outcome. The cut-off points of each correlating RS-point values were defined and tested towards predicting the DFS. The performance of predicting the power of spectral points was validated through Brier value, and it was found to be closer to the actual progression. The 76 spectral points identified from the tumors have the potential to accurately predict DFS in oral squamous cell carcinoma through a relatively simplistic prediction model in the absence of confounding factors., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

Background: Narrow band imaging (NBI) is a novel method with the potential to improve the diagnostic capability of white-light., Methods: A prospective observational study of 50 consecutive patients, with suspicious malignant/premalignant lesions. White-light images were assessed as suspicious for malignancy/negative for malignancy, whereas NBI images were classified based on the IPCL patterns. All lesions underwent biopsy and accuracy was compared with the histopathology (Fig. 1). Fig. 1 Representative images of the IPCL patterns from Types I-IV RESULTS: 25 lesions (49%) were positive for malignancy, 2 (3.9%) lesions showed severe dysplasia, and 24(47%) were considered negative on histopathology. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of white light and NBI in detecting invasive carcinoma was 74.07%, 79.17%, 80.00%, 73.08% and 76.47%, and 92.67%, 90.16%, 92.56%, 91.67% and 92.16% respectively. The NBI group had a significantly better sensitivity and specificity to white light. The interobserver concordance was κ = 0.881., Conclusion: NBI is a highly effective tool to detect invasive carcinomas amongst suspicious lesions of the oral cavity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Overexpression of anti-apoptotic MCL-1 protein in oral squamous cell carcinoma (OSCC) is linked to disease progression, therapy resistance and poor outcome. Despite its characteristic short half-life owing to ubiquitin-proteasome-dependent degradation, oral tumours frequently show elevated MCL-1 protein expression. Hence, we investigated the role of deubiquitinase USP9X in stabilising MCL-1 protein and its contribution to oral tumorigenesis., Methods: Expression of MCL-1 and USP9X was assessed by immunoblotting and immunohistochemistry in oral cancer cell lines and tissues. The association between MCL-1 and USP9X was confirmed by coimmunoprecipitation and immunofluorescence. Cell death assessment was performed by MTT, flow cytometry and clonogenic assays., Results: Both USP9X and MCL-1 are significantly elevated in oral premalignant lesions and oral tumours versus normal mucosa. USP9X interacts with and deubiquitinates MCL-1, thereby stabilising it. Pharmacological inhibition of USP9X potently induced cell death in OSCC cells in vitro and in vivo. The elevated expression of USP9X and MCL-1 correlated with poor prognosis in OSCC patients., Conclusion: We demonstrate the oncogenic role of USP9X in driving early-to-late stages of oral tumorigenesis via stabilisation of MCL-1, suggesting its potential as a prognostic biomarker and therapeutic target in oral cancers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Evidence for performing contralateral neck dissection (CND) of recurrent oral cavity squamous cell cancers (OCSCC) is lacking., Material and Methods: This is a retrospective study of 78 consecutive OCSCC having ipsilateral recurrence recorded over five years. We screened 1658 OCSCC patients and selected those patients who underwent CND as part of treatment for ipsilateral recurrence., Results: The median disease-free interval was 32 months. Incidence of contralateral nodal metastasis (CNM) in recurrent OCSCC was 23.1% and of which 14% were occult. The factor significantly influencing CNM was the depth of invasion (DOI) > 10 mm (p < 0.01). In our study, imaging had suboptimal PPV (33%) while it had high NPV (88%) in diagnosing nodal metastasis in recurrent OCSCC., Conclusion: DOI is the most important factor predicting CNM in case of ipsilateral primary recurrence. PET-CECT has a high NPV and contralateral neck should be addressed in case of tumours with higher DOI., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Importance: Follow-up assessment of patients who had treatment for head and neck cancer is critical and an important part of the overall treatment program. During each visit to the hospital, patients are evaluated by a physician and may undergo additional tests. Because it has been observed that the symptoms mentioned by patients often guide the treating clinicians in identifying cancer recurrence, an appropriately constructed questionnaire can help clinicians determine which patients need further testing as a result of a recurrence and which patients can continue to be monitored remotely., Objective: To evaluate the role of a symptom-based telephone questionnaire in detecting recurrences in patients with radically treated oral cancer., Design, Setting, and Participants: This prospective diagnostic cohort study was conducted from October 1, 2018, to February 28, 2019. This study took place at Tata Memorial Centre, an apex referral cancer center in India. A total of 615 consecutive patients with oral cancer were screened, of whom 400 patients consented to be a part of the study. After completion of curative treatment, these patients were followed up for 2 months to 2 years. We excluded patients younger than 18 years or older than 80 years, those with Eastern Cooperative Oncology Group status greater than 2, and those who had already been diagnosed with recurrent disease., Interventions/exposures: The patients were contacted 2 weeks before their clinic appointment, and a telephone interview was conducted using a predefined questionnaire. Based on patients' responses to these questions, their disease status was estimated. Subsequently, during the actual follow-up visit, a trained head and neck surgeon, who was blinded to the questionnaire result, examined them., Main Outcomes and Measures: The sensitivity and specificity of the telephone questionnaire were calculated by comparing its results with those of the trained head and neck surgeon after the clinical evaluation., Results: Of the 615 patients screened, 400 consented to be part of the study. Participants had a median (interquartile range) age of 49 (41-56) years, and 334 (83.5%) were men. Recurrence was noted in 20 patients (5.0%). The telephone-based questionnaire was found to have sensitivity of 90.0%, specificity of 74.2%, positive predictive value of 15.5%, and negative predictive value of 99.3%. Clinical examination values were 100.0%, 92.9%, 42.5%, and 100.0%, respectively. A total of 124 patients (31.0%) said that they would prefer such a telephone follow-up compared with an actual physical follow-up visit., Conclusions and Relevance: This diagnostic cohort study found that a symptom-based telephone questionnaire had good sensitivity and negative predictive value for detecting recurrences in patients with oral cancer on follow-up evaluation after completion of definitive treatment.

Background: The literature often cites margin status as being free, close or involved by tumor but there is very sparse evidence of the relevance of dysplasia at resection margin. Aims/Objectives: To compare the impact of dysplasia at final resection margin (D-FRM) and other margin statuses on overall survival (OS) and disease free survival (DFS)., Methods: This is a retrospective review of 1700 treatment naïve oral squamous carcinoma patients who underwent surgery between January 2012 and December 2015. The study arm consisted of patients with dysplasia at final resection margin (D-FRM). Each of these patients were double propensity matched to obtain positive (P-FRM), close (C-FRM) and free final resection margins (F-FRM)., Results: There was no hazard discrimination in survival among the D-FRM and C-FRM (vs F-FRM; p-0.597, HR-1.207 (0.621-2.346) and p-0.075, HR-1.594 (0.947-2.684), respectively). A decreasing survival trend was observed as the grade and number of D-FRM margins increased. Although not significant, the addition of adjuvant therapy for D-FRM showed a trend towards improved survival outcomes compared to C-FRM, especially with chemotherapy. Conclusion and relevance: The presence of D-FRM, irrespective of grade, had a similar impact on survival as C-FRM and underscores the possible need for treatment intensification.

Background: Sarcomatoid variant of oral squamous cell carcinoma (OSCC) is aggressive tumors that frequently recur and metastasize. Our aim was to determine the survival outcomes and factors that predict its incidence in recurrent and second primary tumors (SPT)., Methods: We retrospectively analyzed the records of SPT and recurrent OSCC cases with sarcomatoid differentiation. The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method. Logistic regression was used to identify the factors associated with SPT and recurrent sarcomatoid OSCC. Recursive partitioning was performed to classify the sample based on the clinicopathological factors of the index tumor., Results: A total of 82 patients were included in the study with a median survival, calculated from the date of diagnosis of recurrence or SPT, of 6 months (recurrence-2 months, SPT-8 months). The 3-year OS for the recurrence group was 19.9% and for SPT group was 29%. Perineural invasion in the index tumor was significantly associated with sarcomatoid differentiation in the recurrent tumor. At one end of the spectrum of the recursive partitioning were the SPTs that had small index tumor sizes and DOI/thickness less than 14.5 cm (lowest risk), and at the other end were recurrent diseases that had index tumors of advanced T stage (highest risk)., Conclusion: Sarcomatoid variant in the recurrent/SPT OSCC infers a poor prognosis. Recurrent disease that had an index tumor with advanced T stage carries the worst outcomes. Perineural invasion in the index tumor can help predict the presence of sarcomatoid carcinoma in the recurrent or SPT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Soft tissue deposit (STD) is the presence of tumor foci in the neck at sites other than lymphoid tissue. We evaluated the factors associated with STD and their impact on outcomes., Methods: The records of 4812 treatment naïve oral cancers operated between December 2010 and September 2015 were screened for the presence of STD. A matched-pair analysis was performed to obtain 450 patients without STD. Chi-square was used to test association with clinicopathological factors and hazard ratio (HR) for overall survival (OS) and disease-free survival (DFS) were calculated., Results: STD was present in 0.6% and associated with gingiva-buccal cancers, advanced stage, poor differentiation, presence of extranodal extension (ENE) and higher locoregional/distant metastasis. They had a significantly poorer OS (HR-2.08; P-value .0073) and DFS (HR-2.5; P-value .0002) with and without ENE [HR-1.96 and 3.7, respectively]., Conclusion: Despite aggressive adjuvant therapy STD has a significant negative impact on outcomes., (© 2020 Wiley Periodicals, Inc.)

The aim of our study was to evaluate the predictive ability of the American Joint Committee Cancer (AJCC) eighth edition (AJCC8) staging system for oral cavity cancers and validate these changes rendering the hypothesis of improving prognostication. We conducted a retrospective study including all oral cavity squamous cell carcinoma patients visiting our tertiary center from 2012 to 2015, staged as per the AJCC seventh edition (AJCC7) and AJCC8 systems. Stage-specific disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Concordance index (CI) and Akaike information criterion (AIC) were used to calculate the predictive accuracy of the both systems. The study sample consisted of 863 subjects followed up for a median of 24 months. Buccal mucosa complex (BMC) was the most common site (n = 496). We observed a 25.8% (n = 222) overall upstaging in the eighth edition, significantly seen in early tongue cancers (TCs) (Stage I) and advanced BMC cancers (Stage III). An increase in CI and reduction in AIC scores were indicative of a superior predictive accuracy for the eighth edition in assessing DFS (confidence interval [CI*] = 0.650-0.654; AIC = 3,022-3,014) and OS (CI* = 0.643-0.648; AIC = 2089-2086) across all stages. The accuracy was higher for TCs as compared to BMC. Although not statistically significant, we observed an increase in soft risk factors at higher stages in the eighth edition as compared to its predecessor. We concluded that the AJCC8 has a higher predictive accuracy than the AJCC7 edition, making it a reliable prognosticative tool., (© 2019 UICC.)

Oral squamous cell carcinoma (OSCC) is highly prevalent in south and southeast Asia. Many (30-50%) OSCC patients develop lymph node metastasis (LNM), which is the most important prognostic factor in OSCC. To identify genomic correlates of LNM, we compared exome sequences and copy number variation data of blood and tumor DNA from highly contrasting subgroups of patients to reduce false inferences-(i) patients with LNM and (ii) patients with late stage disease but without LNM. We found that LNM is associated with (i) specific hotspot somatic mutations in TP53 and CASP8; (ii) rare nonsilent germline mutations in BRCA2 and FAT1; (iii) mutations in mito-G2/M and nonhomologous end joining (NHEJ) pathways; (iv) recurrent deletion of genes for DNA repair by homologous recombination; and (v) chromosomal instability. LN+ patients with NHEJ pathway mutations have longer disease-free survival. Five genomic features have a high predictive value of LNM., (© 2019 UICC.)

Oral cancer is associated with high rates of recurrence, attributable to field cancerization. Early detection of advanced field changes that can potentially progress to carcinoma can facilitate timely intervention and can lead to improved prognosis. Previous in vivo studies have successfully detected advanced field effects in oral cancers. Raman exfoliative cytology has previously shown to differentiate normal, oral pre-cancer and cancers. The present study explores Raman-exfoliative-cytology-based detection of field effects. Exfoliated cells were collected from tumor (n = 16) and contralateral-normal appearing mucosa (n = 16) of oral cancer patients, and healthy tobacco habitués (n = 20). After spectral acquisition, specimens were Pap-stained for cytological evaluation. Data analysis, by Principal Component Analysis and Principal Component-Linear Discriminant Analysis, indicate several spectral-misclassifications between contralateral normal and tumor, which were investigated and correlated with spectral, cytological and clinical outcomes. A qualitative analysis by grouping patients with number of misclassifications with tumor (Group 1: 0, Group 2: 1 and Group 3: >1) was explored. Group 3 with highest misclassifications showed spectral and cytological similarity to tumor group - one patient was a case of early inoperable residual disease, despite clear margins on histopathology. Thus, these misclassifications could be indicative of cancer field changes, and can prospectively help to identify patients susceptible to recurrences ., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The objective of this study was to evaluate the utility of frozen section (FS) in detecting occult nodal metastasis in cN0 OSCC and its impact on regional failure and survival., Materials and Methods: Clinical records of patients of OSCC operated from January 2013 to December 2014 were retrospectively reviewed. These patients were divided into two groups-Group A comprised of patients who underwent selective neck dissection (SND) (level III/IV) and FS based completion (level IV ± V); Group B included patients who underwent SND I-III/IV without FS. The sensitivity and specificity of FS in detecting occult metastasis was calculated. The regional failure rates and overall survival (OS) between the two groups were compared., Results: The sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of FS in detecting occult metastasis were 64.06%, 100%, 100%, and 92.15%, respectively. There was no significant difference in regional failure rates (p = 0.219) and OS (p = 0.08) between the two groups., Conclusion: FS has a poor sensitivity in detecting occult nodal metastasis. FS-guided neck dissection does not have a significant impact in reducing regional failure or improving OS in clinically node-negative neck in oral cavity carcinomas.

Fabrication and testing of a novel nanostructured surface-enhanced Raman catheter device is reported for rapid detection, classification, and grading of normal, premalignant, and malignant tissues with high sensitivity and accuracy. The sensor part of catheter is formed by a surface-enhanced Raman scattering (SERS) substrate made up of leaf-like TiO 2 nanostructures decorated with 30 nm sized Ag nanoparticles. The device is tested using a total of 37 patient samples wherein SERS signatures of oral tissues consisting of malignant oral squamous cell carcinoma (OSCC), verrucous carcinoma, premalignant leukoplakia, and disease-free conditions are detected and classified with an accuracy of 97.24% within a short detection-cum-processing time of nearly 25-30 min per patient. Neoplastic grade changes detected using this device correlate strongly with conventional pathological data, enabling correct classification of tumors into three grades with an accuracy of 97.84% in OSCC. Thus, the potential of a SERS catheter device as a point-of-care pathological tool is shown for the rapid and accurate detection, classification, and grading of solid tumors., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Surgical margin is one of the most important prognostic factors in oral cavity squamous cell carcinoma. There have been studies which refute the standard practice of considering 5 mm (mm) margin as free. Therefore we aimed to evaluate the impact of each mm of margin on the local recurrence free survival (LRFS) and to obtain a cut-off value which would impact the survival the most., Material and Methods: This was a retrospective study of 602 treatment naïve patients of buccoalveolar complex cancer. ROC curve was plotted for each millimetre of margin to derive the cut-off margin for maximum LRFS. Multivariate analysis was done for the margin groups to calculate the margin beyond which no significant improvement on LRFS was achieved. Early and advanced tumors were also evaluated separately., Results: A cut off margin of 5.5 mm was achieved on ROC for early (T1-T2) tumors and 6.5 mm cut off was achieved for advanced (T3-T4) tumors. Based on these cut off different margin groups were made. The cohort was grouped into positive margin, 1-5.5 mm, 5.6-7 mm and > 7 mm. Hazard ratio for patients with 1-5.5 mm and positive margin was 1.886 (95%CI, 1.15 to 3.09) and 5.58 (95%CI, 1.75 to 17.78) respectively. HR for margin 5.5 mm to 7 mm was 1.15 (95% CI, 1.15 to 2.06). There was no statistically significant difference in survival between margin groups of 5.6-7 mm and > 7 mm (p < 0.589) for both early and advanced tumors., Conclusion: Minimum surgical margins of 5.5 mm in the final histopathology should be aimed for in the bucco-alveolar carcinomas. There was significant improvement in LRFS with increasing margins upto 7 mm. Taking margins beyond 7 mm does not improve LRFS., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: A sea of literature addressing the adequacy of mucosal/soft tissue surgical margins in oral cavity cancers is available, but no mention exists regarding bony margins. We aim to study the predictors and impact on survival of positive bony margins and propose a safe margin distance., Methods: This is a retrospective study of 400 consecutive surgically treated pT4 oral cavity squamous cell carcinoma patients between January 2012 and December 2015. The factors predicting positive bony margins were determined using chi-square test. Kaplan Meier and Cox regression hazard models were used for survival analysis. The median follow up was 36 months., Results: The only factor that significantly predicted positive bony margins was lymphovascular emboli. The 3-year OS with bony margin positivity was 36.9%, compared to 67.5% for patients with adequate margins. When the tumor infiltrated the bone beyond mucosa (20.25%) the survival outcomes were significantly worse than the other patterns. Microscopic spread was seen in 10% cases, at a distance of 8 mm, the presence of which significantly impacted survival outcomes. Analysis of the receiver operating curve identified a cutoff of more than 15 mm as appropriate for classifying adequate bony margins. When the margins were taken above this, a significant positive impact on survival outcomes was present., Conclusion: The presence of lymphovascular emboli may impact the status of bony margins. Based on our results, to achieve an "adequate margin in bone" we propose taking the bony cut at least 15 mm away from the clinically discernible tumor when treating advanced oral cancers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: In this study we have tried to analyze the impact of age on various clinico-pathological parameters, treatment completion and subsequent survival in older patients., Materials and Methods: This is a retrospective analysis of 140 elderly (> 65 years) patients of oral cancer operated between January 2012 and December 2013. The patients were divided into two groups based upon their age that ≤ 70 years and > 70 years.Association of distribution of various clinico-pathological factors between different groups was assessed by using Chi-square test. Survival analysis was done using Kaplan Meir analysis. Univariate and multivariate analysis were performed., Results: The two groups had similar distribution of various clinico-pathological factors. Disease free survival for the group ≤ 70 and > 70 years was 37.6 months and 36.4 months (p < 0.594). 13.5% and 7.8% patients > 70 years and ≤ 70 years were either advised or received sub-optimal adjuvant therapy (p < 0.002)., Conclusion: There is no difference distribution of various clinico-pathological factors and survival in patients of oral cancer ≤ 70 and > 70 years of age. Age did not affect survival. Majority of patients could complete the adjuvant therapy advised. Still, significantly more number of patients > 70 years could not receive/complete appropriate adjuvant therapy. Thus treatment needs to be tailored keeping in mind the individual's performance status and the co-morbidities.

Background: Routine use of frozen section (FS) is a costly procedure and sparsely available in resource poor countries. A proper cost benefit analysis may help to reduce its routine use and would empower surgeons to perform oral cancer surgeries without having FS facility. FS is performed to identify microscopic spread beyond gross disease that cannot be assessed clinically., Objective: Our primary aim was to determine the cost benefit analysis of FS in the assessment of margins in oral cavity squamous cell carcinoma (OSCC)., Materials and Methods: Retrospective study of prospectively collected data of 1311 consecutive patients who were operated between January 2012 and October 2013. The gross and microscopic margin status of each patient was extracted from the patient's chart. The cost estimates were performed to calculate the financial burden of FS as well as expenses incurred on adjuvant treatment resulting from inadequate margins., Result: Microscopic spread changed the gross margin status in 5.2% (65/1237) patients. Of this entire cohort of 1237 patients, FS helped 29 (2.3%) patients to achieve tumor free margin, and it changed the adjuvant treatment plan in 9 (0.7%) patients. The cost of FS for each patient was INR 11052. The cost-benefit ratio of FS was 12:1. Gross examination alone could have identified majority of the inadequate margins., Conclusion: Frozen section for assessment of margin status bears poor cost-benefit ratio. Meticulous gross examination of the entire surgical specimen is sufficient to identify majority of inadequate margins., Competing Interests: There are no conflicts of interest.

Objective: Globally oral cancer is one of the ten most common cancers with prevalence being high in Central and South East Asian countries. This survey was conducted to estimate the prevalence of oral pre-malignant lesions (OPML) and to identify their risk factors. Methods: A community based cross-sectional study was carried out among 2033 individuals aged ≥18 years. A questionnaire was administered to collect socio-demographic characteristics, various risk factors for oral cancer and presence of its symptoms. Oral cavity of all the participants was examined in detail by the study investigator as per WHO guidelines for the early diagnosis of oral neoplasia. Result: The prevalence of OPML was found to be 3.73%. Among those with OPML, all were ever tobacco consumers and had poor oral hygiene. A significant association was observed between OPML and younger age group (OR=2.56, 95% CI 1.08-6.02), males (OR=26.76, 95% CI 8.40-85.19) and low socio-economic status (OR = 1.91, 95% CI 1.20-3.02). Tobacco (p<0.001), alcohol (OR= 7.92, 95% CI 4.77-13.14) and areca nut consumption (OR = 5.48, 95% CI 3.42-8.77) were strongly associated with OPML. On multivariate analysis among ever tobacco users, OPML was associated with younger individuals, males and those using smokeless forms of tobacco (p <0.05). The study showed that the participants with OPML were more likely to be never married (OR=1.6, 95% CI 0.92-2.96),to be unskilled workers (OR= 1.45, 95% CI 0.61-3.43), to have suffered from oral trauma (OR =1.30, 95% CI 0.75-2.26), to have consumed hot and spicy food frequently (OR=1.53, 95% CI 0.96-2.24), to have consumed fruits infrequently (OR=1.53, 95% CI 0.90-2.59) and to report family history of any cancer (OR = 1.29, 95% CI 0.58-2.87) . However, these associations were statistically insignificant. Conclusion: The study reinforces that use of substances such as tobacco, alcohol and areca nut are the modifiable risk factors for OPML., (Creative Commons Attribution License)

Background: Controversy exists regarding the administration of adjuvant radiotherapy (RT) when perineural invasion (PNI) is the only adverse histological feature. The purpose of this study was to evaluate the impact of PNI on the survival of patients with oral cavity squamous cell carcinoma (SCC)., Methods: A retrospective study of 1524 treatment naive patients with oral cavity SCC who underwent surgery from January 2012 to March 2015 was conducted. Survival analysis was performed using Cox regression model., Results: The incidence of PNI was 20.3% and higher in tongue cancers (odds ratio 2.43). The PNI significantly affected both disease-free survival (DFS; hazard ratio [HR] 1.84) as well as overall survival (OS; HR 1.7). Patients with early node-negative oral cavity SCC with PNI are more likely to develop recurrences and have mortality (HR 2.79 for DFS; HR 2.54 for OS). However, the addition of adjuvant radiation in these patients showed improvement in survival (p = .022). Forest plot analysis showed a trend toward poor survival across all subgroups in patients with PNI., Conclusion: Aggressive treatment of the primary cancer with the coincident management of the neck is important in the presence of PNI. The PNI worsens survival and warrants intensification of adjuvant treatment., (© 2018 Wiley Periodicals, Inc.)

Introduction: In the absence of any robust data supporting the TNM classification of T4 buccal mucosa cancers, we did this prospective study to compare the oncologic outcomes of T4a and T4b buccal mucosa cancer patients., Patients and Methods: This is a prospective study of 210 treatment naïve T4 buccal mucosa cancer patients. All patients underwent upfront radical surgery followed by adjuvant radiotherapy (RT)/chemoradiotherapy (CCRT). This is the largest prospective series in the literature on T4 buccal cancers., Results: T4a disease was seen in 135(64.3%) patients and T4b in 75(35.7%) patients. On comparison between all T4a and T4b cases, a significant difference was observed with regard to 3-year local control (49.6% vs. 41.1%: p-0.025) and disease-free survival (DFS) (65.3% vs. 42%: p-0.035) with a slightly higher incidence of distant metastasis in T4b patients (17.3% vs. 9.6%). Inadequate cut margin (<5 mm) was seen only in 7.4% patients with T4a disease and 12% patients with T4b disease. When patients with adequate cut margins were considered for analysis, local recurrence rate was similar for T4a (26/135; 19.3%) and T4b (15/66; 22.7%) disease suggesting the importance of radical surgery in infra-notch T4b buccal cancers. While the 3-year survival for T4a patients who received adjuvant RT alone was 72.2%, it was only 42.1% for similar T4b patients suggesting a need to intensify adjuvant treatment for these patients., Conclusion: Surgery should be considered as the primary modality of treatment for T4b patients, where clear margins are achievable. The benefit of treatment intensification with adjuvant CCRT should be explored in T4b buccal cancers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Objectives: T4 squamous cell carcinomas of the buccal mucosa is known to have ominous outcome. The aim of this study was to develop a nomogram for T4 buccal mucosa cancer patients and demonstrate the difference in survival based on prognosticators beyond those covered by the traditional TNM staging system., Methods: We examined medical records of treatment naïve 205 T4 buccal mucosa cancer patients operated between January 1, 2009, and December 31, 2014. A nomogram was developed using multivariate cox-regression. The nomogram was validated internally by bootstrapping and externally in an independent validation set., Results: The nomogram for predicting 3-year overall survival was built using Tumor differentiation, Pathological Lymph node involvement, Bone and Perineural invasion. Based on nomogram, a score was assigned to each patient and they were divided into two groups based on Youden derived cut-off value (13.5). These two groups in training and validation set showed significant difference in survival., Conclusion: We developed a high performance, accurate and efficient nomogram to predict the probability of 3-year survival in T4 buccal mucosa cancer patients. Intensification of adjuvant treatment in these advanced cancer patients with poorer score might improve their survival., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Presence of extracapsular spread (ECS) significantly decreases survival in oral cancer patients. Considering its prognostic impact, we have studied the incidence and factors predicting ECS in clinically node negative early oral cancers., Materials and Methods: We performed a retrospective chart review of 354 treatment naïve clinically node negative early oral cancer patients operated between 2012 and 2014. Chi-square test and logistic regression were used for identifying predictors of ECS, while cox-regression test was used for survival analysis., Results: The incidence of occult nodal metastasis was 28.5% (101/354). Among them, ECS was seen in 15.3%(54/354) patients. The incidence of ECS in T1 and T2 lesion was 13.4% (21/157) and 16.8% (33/197), respectively. The overall incidence of ECS was 48% and 29% in lymph nodes smaller than 10 mm and 5 mm respectively. We found that tumor depth of invasion (>5 mm; p-0.027) and node (metastatic) size >15 mm (p-0.018) were significant predictors of ECS. p N2b disease was seen in 41/354 (11.6%) of which 31/354 (8.7%) had ECS, i.e. 75.6% of pN2b patients been ECS positive (p-0.000). The 3-year OS of patients without nodal metastasis, nodal metastasis without ECS and nodal metastasis with ECS was 88.4%, 66.9% and 59.2% (p-0.000) respectively., Conclusion: A significant number of patients with metastatic nodal size less than 1 cm have ECS which suggests aggressive behavior of the primary tumor. Thus, elective neck dissection is the only way of detecting ECS in these patients which may warrant treatment intensification., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Quality of life (QOL) has become an important aspect of today's health care management. This study performed longitudinal assessment of QOL in patients with advanced cancers of the buccal mucosa (T4). We compared the QOL between patients who received adjuvant chemoradiation therapy (CTRT) and that of patients who received radiation therapy alone and assessed whether baseline QOL can predict disease recurrence., Study Design: This was a prospective study of 225 patients with T4 buccal mucosal cancer. Health-related QOL was assessed at baseline and at 3, 6, 9, and 12 months after completion of treatment by means of the European Organization for Research and Treatment of Cancer Core QOL Questionnaire and the HN35 questionnaire., Results: There was persistent improvement in global QOL and pain. Emotional functioning improved at 12 months. Most of the head and neck-specific symptoms deteriorated at 3 months, with subsequent improvement at 12 months except in swallowing, senses, speech, social eating, social contact, and sexuality. Patients who received adjuvant CTRT had poorer QOL. Poorer baseline global QOL (P = .049), dyspnea (P = .04), appetite loss (P = .015), and weight loss (P = .08) may predict recurrence., Conclusions: Although there is an improvement in global QOL and pain, most of the head and neck-specific symptoms worsened in the immediate postoperative period. Adjuvant CTRT has a persistent effect on specific domains compared with adjuvant radiation therapy alone. Poor baseline QOL scores are associated with a higher risk of recurrence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Higher rates of local recurrences and second primaries, ascribable to field cancerization, are known problem in oral cancers. The present study explored utility of identification of potential recurrences by Raman spectroscopy, which has been shown to identify oral precancers, cancers, and field cancerization in humans and micro-sized mechanical irritation-induced tumors in animals., Methods: Raman spectra were acquired from tumor and contralateral normal mucosa in 99 patients with oral cancer who were then followed up for appearance of clinically apparent cancerous lesions. Misclassifications observed in subsequent multivariate statistical analysis between contralateral normal and tumor spectra were correlated with appearance of new malignant lesions., Results: The patients with mismatched spectra had 1.5 times higher chances of developing local recurrence. The sensitivity of Raman spectroscopy in predicting the recurrences was 80% and the specificity was 29.7%., Conclusion: Findings provide proof-of-concept for Raman spectroscopy-based identification of sites that have higher propensity to progress to carcinomas before becoming clinically apparent. Prospective validation of Raman spectroscopy by including additional oral cavity subsites and use of multifiber bundles may improve rate of identification of recurrence-prone subjects., (© 2017 Wiley Periodicals, Inc.)

Background: Oral cancers are one of the most common cancers in India. Surgery is the main modality of treatment for oral cancer patients. It is important to understand the postoperative morbidity and mortality as it influences patient outcomes., Aim: The aim of this study was to determine oral cancer patients' characteristics, treatment details, 30-day morbidity and mortality, and survival outcomes., Settings and Design: This was a retrospective analysis of prospectively collected data in a tertiary cancer center., Materials and Methods: This study included 850 surgically treated oral cancer cases between January and December 2012., Statistical Analysis: We performed univariate survival analysis by log-rank test, and all significant (P < 0.05) variables underwent multivariate analysis using Cox regression., Results: The median age was 52 years and the male-to-female ratio was 3.4:1. Nearly one-third of the patients received some form of prior treatment. Buccal mucosa (BM) was the most common subsite (64.94%). BM cancers (81.1%) were more likely to present in advanced stage compared to tongue cancers (52%) (P = 0.000). The incidence of postoperative morbidity and mortality was 36.4% and 0.9%, respectively. Complications were higher in cT3-4 (P = 0.000), cN positive (P = 0.000), and those requiring microvascular reconstruction (P = 0.004). The 5-year overall survival of the entire study group was 70.4%. The survival of early and locally advanced stages was 75.1% and 68.4%, respectively. The factors influencing survival were age (>50 years), advanced cT stage, nodal metastasis, overall stage, and presence of orocutaneous fistula., Conclusion: The morbidity, mortality, and long-term outcomes of surgically treated oral cancer patients at our center are comparable to those treated in the developed world. Aggressive management of postoperative complications is crucial for early recovery and timely initiation of adjuvant treatment., Competing Interests: There are no conflicts of interest

Objective: Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with the use of areca nut, and is mainly seen in the parts of Southeast Asia and the Indian subcontinent. We hypothesized that oral cancers occurring in presence of OSMF are clinicopathologically a distinct entity., Study Design: We analyzed 289 treatment naïve patients of oral cancer. They were followed up for a median of 44 months. Association of presence of OSMF with other histopathological factors was done using the χ 2 test. Kaplan-Meier analysis was used for survival analysis., Results: Oral squamous cell carcinoma along with OSMF was seen more often in younger patients (P < .001) and males (P < .007), and had a lower T-stage (P < .002) and N-stage (P < .000). These were thinner (P < .002), less infiltrative (P < .04) tumors and required adjuvant therapy less frequently (P < .017). The mean disease specific survival, overall for those with and without OSMF was 58.8 and 48.6 months (P < .002), and specifically for stages III and IV was 49.4 and 38.5 months, respectively (P < .053)., Conclusions: Oral squamous cell carcinomas associated with OSMF are associated with good clinicopathologic profile and have better prognosis and oncological outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Despite meticulous surgery and proper adjuvant treatment, outcome of oral squamous cell carcinoma remains unpredictable. This shows that there may be other factors which should be considered while prognosticating these patients. Many a times there is spread of disease beyond the gross margin which can alter the margin status. We hypothesized that microscopic spread beyond gross disease may portend a poor prognosis., Method: This is a retrospective study of prospectively collected data of 1025 treatment naïve oral squamous cell carcinoma patients. All patients underwent surgery from January 2012 to October 2013, this was followed by appropriate adjuvant treatment. Demographic and histopathological details were noted from the electronic medical records., Results: Microscopic spread beyond gross disease (MSGD) is associated with higher incidence of nodal positivity (p < 0.046), peri-neural invasion (p < 0.001), thicker tumours (p < 0.024) and poor differentiation (p < 0.060). The overall survival in patients with MSGD was 32.45 months vs. 37.5 months in patients without MSGD (p < 0.002)., Conclusion: Tumours with MSGD tend to have a higher incidence of nodal metastasis, PNI and thicker tumours. Presence of MSGD was associated with lower overall survival as compared to those without., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: Surgical margin status is an important prognostic factor in oral squamous cell carcinoma. The primary aim of the surgeon is to achieve a microscopically complete surgical resection during initial surgery. As there are no definite guidelines, a few surgeons use frozen section (FS) for margin assessment whereas others use gross examination (GE)., Study Design: This is a retrospective analysis of prospectively collected data from the electronic medical records of 435 oral cavity cancer patients. As per the operating surgeon's preference, margin assessment was done using GE in 239 (54.94%) specimens, and FS was used in 196 (45.05%) specimens. Surgery was the primary modality of treatment for all patients, followed by adjuvant therapy., Results: Close/positive margins were seen in 6.63% of patients in the FS group and in 6.69% of patients in the GE group (P = .855). The sensitivity and specificity were 45.45% and 98.8%, respectively, for FS and 61.9% and 88.32% for GE. We found no survival benefit when FS was used for margin assessment (disease-free survival: P = .469; overall survival: 0.325). Incidence of inadequate margins was similar in both the groups (P = .608) even in patients with some form of previous treatment., Conclusion: We propose the judicious use of FS rather than routine use for margin assessment. The study reports that GE is an well-tolerated oncologic alternative to FS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The submandibular gland is responsible for 70% to 90% of unstimulated saliva production. Its excision causes a decrease in basal salivary flow resulting in increased symptoms of subjective xerostomia and decreased quality of life. In this study, we have tried to assess the pattern of nodal metastasis in relation to the submandibular gland. With this study, we have tried to find out whether submandibular gland preservation is a viable option in patients with carcinoma of the oral cavity., Methods: This was a prospective study conducted in a tertiary care cancer center. The fibrofatty tissue surrounding the submandibular gland was divided into 6 parts depending upon its location with the submandibular gland. All these 6 parts along with the submandibular gland were separately sent for histopathological analysis. Metastasis pattern in level Ib region was noted., Result: The study included 137 patients with carcinoma of the oral cavity who underwent neck dissections. Eighty-five patients had clinic-radiologically N0 neck, 52 patients had cN+ (clinically node positive) neck. Level Ib was involved in 8.2% of the cases with cN0 (clinically node negative neck). In patients with cN+ neck, level Ib metastasis was seen in 40% of the cases. Metastasis in N0 necks in the area deep to the submandibular gland was seen in only 1 case (9% of all pathologically node-positive patients) with cN0 neck. This was the only case in which submandibular gland mobilization would have been required to take out the metastatic node. Even in cases with N+ neck, deep metastasis was seen in 4 cases only (14.8%). None of them had a primary tumor in the tongue. Therefore, there is a possibility of preserving the submandibular gland in cases of carcinoma of the tongue., Conclusion: Involvement of level Ib in early tongue cancers is not very common and direct metastases to the submandibular glands are rare. Even when metastasis is present in level Ib, it can be excised without affecting the submandibular gland. In early tongue lesions, submandibular gland mobilization for dissection at level Ib is not required as no metastases deep to the submandibular glands were seen in these patients. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications., Patients and Methods: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed., Results: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment., Conclusions: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Context: In view of low incidence of contralateral nodal metastasis and increase in the morbidity, the opposite neck is not routinely addressed. However, contralateral nodal metastasis is seen frequently in a certain group of patients. Identifying those factors associated with higher chances of contralateral nodal metastasis may help in optimizing the treatment., Aims: The aim of this study was to identify prognostic factors associated with contralateral nodal metastasis in cases of buccal mucosa cancers., Settings and Design: A retrospective audit of 125 patients with squamous cell carcinoma of buccal mucosa at a tertiary cancer center., Subjects and Methods: Those cases in which lesions were reaching or crossing midline were included in this study. All cases underwent surgery as primary modality of treatment and had bilateral neck dissection., Statistical Analysis Used: Chi-square test is used for evaluating the variables predicting contralateral nodal metastasis. Finally, a multivariate analysis was performed using binomial logistic regression to identify those variables that were independently associated with the risk of contralateral nodal metastasis., Results: Among 125 patients, 53 cases were node negative. Ipsilateral nodal metastasis was seen in 44/125 (35.2%) patients, 26/125 (20.8%) had bilateral neck node metastasis, and 2/125 (1.6%) had isolated contralateral nodal metastasis. Among these 28 patients with contralateral nodal metastasis, 26 patients had ipsilateral nodal metastasis. Ipsilateral nodal metastasis and skin involvement were independently predictive of contralateral nodal metastasis., Conclusions: Contralateral nodal metastasis in the absence of ipsilateral nodal metastasis is very rare and frozen section of ipsilateral neck dissection specimen can be an important pointer for addressing contralateral neck.

Angiogenesis in oral squamous cell carcinomas (OSCC) is essential for its growth, invasion, and metastasis. This entails a shift in the balance between proangiogenic and antiangiogenic factors. CD105 and TGF-β1 are 2 such proangiogenic factors wherein CD105 exerts its angiogenic effect by binding to and modulating the TGF-β1 pathway. A total of 50 resected specimens of OSCC were considered. One tissue specimen was taken from tumor proper and another specimen from adjacent apparently normal mucosa (AANM). Both tissues were immunohistochemically stained using CD105 and TGF-β1 antibodies. The expression of each antibody was individually assessed and then compared. Pearson χ test was used for statistical comparison of expression. CD105 was significantly expressed in OSCC as compared with AANM and also correlated with increasing TNM stage. The mean microvessel density was higher in OSCC. TGF-β1 was significantly expressed in epithelium of OSCC as compared with AANM. On comparing expression of TGF-β1 and CD105, 79.54% of endothelial cells expressed positivity for both molecules. Both CD105 and TGF-β1 were increased in OSCC, although based on our results CD105 alone can be used as a prognostic marker. On the basis of immunohistochemical expression of CD105 and TGF-β1 in endothelial cells, our results demonstrate that CD105 acts as one of the receptors of TGF-β1 on endothelial cells and induces the angiogenic pathway in OSCC.

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80%; these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

Background: The purpose of this study was to compare sentinel node biopsy (SNB) and ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative evaluation of the N0 neck in T1 to T2 oral cavity squamous cell carcinoma (SCC)., Methods: Fifty-one consecutive patients with T1 to T2 N0 oral cavity SCC were included in this study. Preoperative ultrasound was performed in all patients. Ultrasound-guided FNAC was performed in patients in whom the ultrasound result was reported as indeterminate or positive. SNB was done in all patients followed by elective neck dissection (END). Histopathology of END was considered as the gold standard for all statistical analysis., Results: The incidence of occult metastasis was 26.4%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.4%, 100%, 100%, and 90.2% for SNB and 14.3%, 100%, 100%, and 76.5% for ultrasound-guided FNAC., Conclusion: Ultrasound-guided FNAC lacked sufficient accuracy to detect occult metastases. SNB is a reliable method to detect occult metastasis that has potential to replace END., (© 2014 Wiley Periodicals, Inc.)

Background: Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate., Methods: In this prospective, randomized, controlled trial, we evaluated the effect on survival of elective node dissection (ipsilateral neck dissection at the time of the primary surgery) versus therapeutic node dissection (watchful waiting followed by neck dissection for nodal relapse) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas. Primary and secondary end points were overall survival and disease-free survival, respectively., Results: Between 2004 and 2014, a total of 596 patients were enrolled. As prespecified by the data and safety monitoring committee, this report summarizes results for the first 500 patients (245 in the elective-surgery group and 255 in the therapeutic-surgery group), with a median follow-up of 39 months. There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group. At 3 years, elective node dissection resulted in an improved rate of overall survival (80.0%; 95% confidence interval [CI], 74.1 to 85.8), as compared with therapeutic dissection (67.5%; 95% CI, 61.0 to 73.9), for a hazard ratio for death of 0.64 in the elective-surgery group (95% CI, 0.45 to 0.92; P=0.01 by the log-rank test). At that time, patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group (69.5% vs. 45.9%, P<0.001). Elective node dissection was superior in most subgroups without significant interactions. Rates of adverse events were 6.6% and 3.6% in the elective-surgery group and the therapeutic-surgery group, respectively., Conclusions: Among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection. (Funded by the Tata Memorial Centre; ClinicalTrials.gov number, NCT00193765.).

Objective: Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients., Materials and Methods: A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naοve at presentation., Results: Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months., Conclusion: The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Objectives: Toll like receptors play an important role in innate and adaptive immune responses. Heat shock proteins play a significant role in cell proliferation, differentiation and oncogenesis. HSP70 acts as one of the ligands of TLR4 and binds to it in a CD14 dependent fashion to bring about proinflammatory cytokine production leading to an anti-tumor response. On the contrary, TLR4 has been implicated in carcinogenesis by secretion of anti-apoptotic proteins. Thus the aim of this study was to compare and correlate the association of HSP70 and TLR4 in various grades of oral squamous cell carcinoma., Study Design: Twenty-seven cases of oral squamous cell carcinoma were considered. Ten cases each of well-differentiated (WDSCC) and moderately differentiated (MDSCC), 7 cases of poorly differentiated carcinoma (PDSCC) were considered. Sections were stained for HSP70 and TLR4 and were evaluated for staining degree and intensity., Results and Conclusion: Positive expression of both HSP70 and TLR4 was found in all cases of WDSCC and MDSCC, whereas in PDSCC out of 7 cases only 6 showed positivity for TLR4 and 4 cases showed positivity for HSP70. Those cases that were positive for TLR4, also showed positivity for HSP70. HSP70 acts as a ligand and binds to TLR4 thus activating the My88 pathway resulting in production of proinflammatory cytokines, chemokines, growth factors etc., enhancing anti-cancer immunity in the early stages of disease. In later stages, TLRs expressed on cancer cells can produce anti-apoptotic proteins contributing to carcinogenesis and cancer cell proliferation.