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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.)

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: During radiation therapy for head and neck malignancies, most patients experience significant anatomical alterations due to loss of weight, changes in tumor volumes, and immobilization issues. Adaptive radiotherapy adapts to the patient's actual anatomy through repetitive imaging and replanning. In the present study, dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer was evaluated., Material and Methods: Thirty-four locally advanced Head and neck carcinoma patients with histologically proven Squamous Cell Carcinoma for curative treatment were included. Rescan was done at the end of 20 fractions of treatment. All quantitative data were analyzed with paired t-Test and Wilcoxon Signed Rank (Z) test., Results: Most patients had oropharyngeal carcinoma (52.9%). There were significant volumetric changes in all the parameters - GTV-primary (10.95, p < 0.001), GTV- nodal (5.81, p = 0.001), PTV High Risk (26.1, p < 0.001), PTV - Intermediate Risk (46.9, p = 0.006), PTV - Low Risk (43.9, p = 0.003), lateral neck diameter (0.9, p < 0.001), right parotid volumes (6.36, p < 0.001) and left parotid volumes (4.93, p < 0.001). Dosimetric changes in the organs at risk were non-significant., Conclusion: Adaptive replanning has been seen to be labour intensive. However, the changes in the volumes of both target and the OARs credit a mid-treatment replanning to be done. Long term follow-up is required to assess locoregional control after adaptive radiotherapy in head and neck cancer., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation., Methods: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m 2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS)., Results: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel., Conclusion: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

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: 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.)

Atypical fibroxanthoma (AFX) is a rare cutaneous ulcerative lesion with a good prognosis. Diagnosis is difficult and is usually made by exclusion from pleomorphic dermal sarcoma and squamous cell carcinoma. Definitive treatment varies from Mohs micrographic surgery to wide local excision. We present a case of 76-year-old woman with AFX over the dorsum of her left hand. The tumour was excised and the resulting defect was reconstructed with a local second dorsal metacarpal artery perforator flap., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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: 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.)

Objectives: We observed that a prominent strip of depapillated mucosa surrounded tongue carcinomas. This study evaluates its correlation with other prognosticating factors., Study Design: This prospective study included treatment naïve squamous carcinomas of tongue operated between January and December 2018. Patients with any disorder that could possibly influence the presence of depapillation were excluded, and stratified based on the presence (Group A) and absence (Group B) of depapillation surrounding the tumor. Data sets included biochemical test, clinical variables, and postoperative histologic features. A multivariate logistic regression was performed to identify the association of these factors., Results: Group A comprised 62.8% (n = 76/121) of the entire cohort, which was reasonably distributed for tumor and host factors. A greater number of inadequate margins were found in Group A. Clinical factors significantly associated with depapillation included higher preoperative platelet count (>250.5), infection rates, and Clavien-Dindo scores. Perineural invasion and lymphocytic infiltrate were significantly associated with Group A, particularly in early tumors (P = .040)., Conclusions: Local invasion and inflammation results in papilla dysfunction clinically appearing as depapillation, leading to accumulation of neurotransmitters and a favorable environment for neural infiltration. We suggest peritumoral depapillation to be a clinical surrogate for perineural invasion, especially in early tongue cancers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.)

Background: As per TNM classification, superficial tumors with a favorable prognosis are fallaciously clubbed together with unfavorable, deeply infiltrating lesions in the same classification., Methods: This is a retrospective study of 588 patients with treatment-naive oral tongue cancers. Binary logistic regression was used to identify predictors of nodal metastasis and extracapsular spread (ECS) using tumor volume and thickness as separate models. The C-index was generated to quantify predictive accuracy of T classification, thickness, and tumor volume for survival., Results: Compared to T classification, tumor volume and thickness were better predictors of nodal metastasis and ECS. Predictive accuracy for disease-free survival (DFS) and overall survival (OS) given by C-index was equal and better for thickness (0.60 and 0.69) and tumor volume (0.61 and 0.69) as compared to T classification (0.59 and 0.64, respectively). For early-stage T1 to T2 oral tongue cancer, thickness is a better predictor of nodal metastasis as compared to tumor volume and T classification., Conclusion: Concordance between the tumor thickness and volume proves that tumor thickness can be taken as a surrogate and reliable predictor of outcomes instead of calculating the tumor volume., (© 2018 Wiley Periodicals, Inc.)

Background: Parotid cancers are uncommon and have a relatively long natural history. Determination of prognostic factors affecting the outcome is difficult., Materials and Methods: The primary objective was to determine the demographic, clinical, histopathology and treatment-related factors affecting overall survival (OS) in parotid cancers. The secondary objective was to study the impact of these factors on disease-free survival (DFS) and patterns of failure. Data of consecutive patients who underwent parotidectomy for primary parotid malignancy between July 2006 and April 2015 with at least 6 months of posttreatment follow-up were retrospectively retrieved. Patients whose follow-up status was known at the time of analysis were included. One hundred and sixty-five patients met the inclusion criteria., Results: The median follow-up was 38 months. The mean OS and DFS were 141.03 and 124.38 months, respectively. Age > 45 years affected both OS and DFS (P = 0.00 and 0.002 respectively) adversely. Advanced T stage affected adversely OS in univariate (P = 0.00) but not in multivariate analysis (P = 0.91) and DFS in both univariate (P = 0.00) and multivariate analysis (P = 0.005). Nodal positivity adversely affected survival adversely in univariate (P = 0.00 for OS and DFS) and multivariate analysis (P = 0.022 for OS and P = 0.001 for DFS). Resection margin of < 5mm affected OS as compared to a margin of ≥5mm (P = 0.03)., Conclusions: Nodal positivity is the single most important factor affecting survival in parotid cancers. A histopathological resection margin of at least 5 mm is desirable. Advanced age along with high grade, advanced T and N stages need to be considered for adjuvant treatment., Competing Interests: There are no conflicts of interest

Head neck squamous cell carcinomas (HNSCCs) are a significant cause of morbidity and mortality all around the world. Just like tobacco and alcohol, Human papilloma virus (HPV) infection is now recognized to play a role in the pathogenesis of a subset of HNSCCs. Unprotected sexual behaviours with the HPV carrier plays an important role in transmission of this virus. The global incidence of head and neck cancers is declining, but the incidence of HPV related head and neck cancers is rapidly increasing over the last few decades. However, most institutions do not mandate documentation of sexual history or counselling of patients regarding sexual practices like they do for tobacco and alcohol addictions in HNSCC patients. The aim of this review of literature is to analyse if there is a strong evidence to correlate oral sex with HPV related HNSCC and counsel the patient's regarding sexual behaviours., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.)

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.)

The objective of this study was to examine the clinical and pathological features of squamous cell carcinoma of the Tongue and Buccal Mucosa and understand their differences. This is a retrospective analysis of prospectively collected data of 735 patients with squamous cell carcinoma of the tongue and 665 cases of carcinoma of the buccal mucosa treated by surgery at our hospital. Statistical analysis was done to examine clinical and pathological differences between carcinoma of the tongue and the buccal mucosa with regards to age, gender, clinical T stage/N stage, pathological T stage/N stage, overall stage, grade, thickness, perinodal extension (PNE), lymphovascular emboli (LVE) and perineural invasion (PNI). Statistically significant differences were found for factors like age (p < 0.001), gender (p < 0.001), clinical T staging (p < 0.001) and pathological stage (p < 0.001), grade of tumor (p < 0.001) and perineural invasion (p < 0.001) between carcinoma of the tongue and the buccal mucosa. Forty-eight percent patients in either subsite had pathologically proven node negative necks (pN0, p = 0.88). Multivariate analysis for occult nodal metastases revealed that predictive factors were different for the two subsites. There are significant differences between cancers of the tongue and buccal mucosa for various clinical and pathological factors. This may be a reflection of the underlying differences in their causation and pathophysiology. Squamous cell carcinoma in these two subsites should therefore be regarded as clinico-pathologically distinct entities.

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.

Background: Notch pathway plays a complex role depending on cellular contexts: promotes stem cell maintenance or induces terminal differentiation in potential cancer-initiating cells; acts as an oncogene in lymphocytes and mammary tissue or plays a growth-suppressive role in leukemia, liver, skin, and head and neck cancer. Here, we present a novel clinical and functional significance of NOTCH1 alterations in early stage tongue squamous cell carcinoma (TSCC)., Patients and Methods: We analyzed the Notch signaling pathway in 68 early stage TSCC primary tumor samples by whole exome and transcriptome sequencing, real-time PCR based copy number, expression, immuno-histochemical, followed by cell based biochemical and functional assays., Results: We show, unlike TCGA HNSCC data set, NOTCH1 harbors significantly lower frequency of inactivating mutations (4%); is somatically amplified; and, overexpressed in 31% and 37% of early stage TSCC patients, respectively. HNSCC cell lines over expressing NOTCH1, when plated in the absence of attachment, are enriched in stem cell markers and form spheroids. Furthermore, we show that inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 inhibits spheroid forming capacity, transformation, survival and migration of the HNSCC cells suggesting an oncogenic role of NOTCH1 in TSCC. Clinically, Notch pathway activation is higher in tumors of non-smokers compared to smokers (50% Vs 18%, respectively, P=0.026) and is also associated with greater nodal positivity compared to its non-activation (93% Vs 64%, respectively, P=0.029)., Conclusion: We anticipate that these results could form the basis for therapeutic targeting of NOTCH1 in tongue cancer., Competing Interests: The authors declare no competing financial interests.

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.

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 and Objectives: Certain tumor-related factors like thickness increases the risk of nodal metastasis and may affect survival in patients with oral tongue cancers. The objective of this study is to identify those tumor-related prognostic predictors that can potentially influence decision for adjuvant radiotherapy., Methods: A retrospective review of all patients with oral tongue cancers treated primarily by surgery at Tata Memorial Hospital between January 2007 and June 2010. The demographic and commonly reported histopathological features were analyzed for their influence on disease free and overall survival., Results: Five hundred eighty-six patients were eligible for the study, of which 416 were males and 117 were females. Follow-up details were available for 498 (85%) patients with a median follow-up of 18 months and mean follow-up of 22 months. There were 302 patients who were alive and disease free at the last follow-up. This group had a mean follow-up of 27 months and median follow-up of 27.5 months. Disease recurrences during follow-up were observed in 184 (31%) patients. Sixty-one patients died subsequently. Perineural invasion significantly affected disease free survival (DFS). A tumor thickness of more than 11 mm significantly affected the overall survival (OS)., Conclusion: Other than nodal metastasis, tumor-related factors like thickness and perineural invasion are adverse prognostic factors and can influence survival. These patients, especially in case of early stage cancers, may potentially benefit from postoperative adjuvant radiotherapy., Level of Evidence: 2b., (© 2014 Wiley Periodicals, Inc.)

Background: The cost-effectiveness of the frozen section for assessment of margin in head and neck squamous cell carcinoma (HNSCC) is still contentious. The purpose of this study was to evaluate whether gross examination of margin is an alternative to frozen section., Methods: It was a prospective observational study in 145 consecutive patients undergoing surgery for HNSCC. Surgical margins were first assessed by the surgeons with a metallic scale. All specimens were then examined using frozen section and permanent section., Results: Overall, 83% of inadequate margins were detected by frozen section. The chances of inadequate margin were very low if gross surgical margin were 7 mm or more. Gross examination alone (with 7 mm as cutoff) predicted 88% of the inadequate surgical margin. There was no difference in precision of frozen section vis-à-vis gross examination with 7 mm cut off (p ≤ .8)., Conclusion: Achievement of 7 mm surgical margin measured by a surgeon obviates the need for frozen section., (Copyright © 2013 Wiley Periodicals, Inc.)

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: To study posterior fossa epidermoids treated surgically at our institute and to compare their long term outcome with respect to extent of surgical decompression., Materials and Methods: Retrospective analysis of 50 cases of posterior fossa epidermoid surgically treated at our institute between 1997 and 2007., Results: The mean duration from onset of symptoms to surgery was 2.5 years. Patients with cerebellopontine angle (CPA) epidermoids presented predominantly with trigeminal neuralgia (35%) and hearing loss (29%) while patients with fourth ventricle epidermoids had features of raised intracranial pressure (ICP) and gait ataxia (69.2% each). The rate of recurrence was 9% in tumors considered totally removed and 93% in those subtotally removed. Of the 17 patients with recurrences, 3 (7.9%) underwent a second operation. The mean duration of follow up at first recurrence was 9.3 years., Conclusion: Based on our experience, the rate of recurrence is significantly higher after subtotal removal as compared to total removal of epidermoids on long-term follow up. Symptomatic recurrence requiring re-exploration is evident only after a long duration (∼10.9 year) following primary surgery. Hence, total removal without producing new neurological deficits should be the standard goal when operating on posterior fossa epidermoid cysts., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: The thyroid gland is removed en bloc during laryngectomy. There are no objective criteria for deciding the extent of thyroid gland resection in primary hypopharyngeal cancer cases. The present study aimed to determine the incidence of thyroid gland involvement in hypopharyngeal cancer and identify the various predictors of this involvement., Method: This paper reports a retrospective analysis of 358 patients with hypopharyngeal cancer, who underwent total laryngectomy with partial or total pharyngectomy at Tata Memorial Hospital, Mumbai between 2004 and 2010., Results: The mean age of this population was 61 years. The pyriform sinus was the most common hypopharyngeal subsite involved (in 89 per cent of cases). Most patients underwent hemi-thyroidectomy as part of their surgery. The thyroid gland was involved in only 13 per cent of cases., Conclusion: Thyroid gland involvement is not common in hypopharyngeal cancer. Cases that involved the post-cricoid area, subglottic extension, extralaryngeal spread or prior tracheostomy were associated with a higher risk of thyroid gland involvement. Ipsilateral thyroidectomy is sufficient in most patients undergoing surgery (laryngectomy with partial or total pharyngectomy) for hypopharyngeal cancers.

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.

Background: Oral cancer is the most common cancer in Indian males and is the third most common cancer in Indian females. Tobacco, alcohol, areca nut, and human papillomavirus (HPV) are the common etiologic factors. Each of these agents follows a unique model of carcinogenesis that leads to a certain distinct presentation and behavior. For example, HPV is strongly associated with oropharyngeal cancers in younger age and is known to have a better outcome and specific histopathologic characteristics. A high incidence of oral submucous fibrosis (OSMF) is linked to areca nut (group 1 human carcinogen) chewing in the Indian subcontinent., Methods: We prospectively studied 371 consecutive patients with proven squamous cell carcinoma of the oral cavity. Of these, 112 patients had oral cancer with OSMF and 259 had oral cancer without OSMF. All patients underwent standard management and their clinicopathologic findings were recorded., Results: We found that patients of oral cancer with OSMF are younger males with better prognostic factors such as better grade of tumor differentiation, lesser incidence of nodal metastases, and extracapsular spread. This difference was maintained even after matching for stage. We also report that presence of OSMF is an independent factor influencing nodal metastases., Conclusions: Based on these findings we propose that oral cancers with OSMF constitute a clinicopathologically distinct disease. Since all patients with OSMF had chewed areca nut with or without smokeless tobacco, we believe that the differences in the 2 groups emanate from differential mechanisms of areca nut carcinogenesis., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: In squamous cell carcinoma of the tongue, when lesions reach or cross the midline, there is a higher risk of contralateral nodal metastasis. Identifying factors that are associated with higher risk of nodal metastasis may help in optimizing the treatment., Methods: A retrospective analysis was conducted of all patients with squamous cell carcinoma of the tongue who had undergone bilateral neck dissection at Tata Memorial Hospital between January 2007 and June 2010 for a lesion crossing or reaching the midline., Results: Contralateral nodal metastases were present in 71 of 243 patients (29%) who underwent bilateral neck dissection. Of these 71 patients, 69 patients (97%) had ipsilateral nodal metastasis., Conclusion: In carcinoma of the tongue, where lesions reach or cross the midline, the chance of contralateral nodal metastases without ipsilateral nodal metastasis is extremely rare. Frozen section of ipsilateral neck dissection can be a pointer for addressing the contralateral neck., (Copyright © 2012 Wiley Periodicals, Inc.)

The aim of this research was to determine the pathologic invasion of the carotid sheath (CS) when found grossly uninvolved during surgery, in patients undergoing neck dissection for head and neck squamous cell carcinoma (HNSCC). A prospective study was undertaken in 70 consecutive patients with biopsy proven HNSCC, without prior history of any treatment, undergoing neck dissection, in whom the CS was found grossly uninvolved intra-operatively, were included. A total of 80 neck dissections were performed. Supra-omohyoid neck dissections for clinically N0 neck and appropriate modified radical neck dissections for clinically N+ neck were carried out. 129 CS were dissected separately and thoroughly examined by well trained head and neck pathologists for tumour infiltration and the presence of lymphatic tissue. On microscopic examination, 27 patients were N0 status and the remaining 43 (61.4%) had at least one metastatic lymph node (N+). None of 129 CS specimens show the presence of normal lymphatic tissue or metastatic tumour deposits. The authors think that avoiding resection of the CS in the absence of gross invasion by nodal disease is possible without jeopardising oncologic safety. A preserved CS might offer protection to the important neurovascular structures and reduce significant morbidity., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: The aims of this study are to evaluate the impact of frozen section in achieving adequate surgical margin and to study the accuracy of frozen section in detection of occult metastases., Materials and Methods: This was a retrospective review of prospectively collected data of 877 patients with squamous cell carcinoma of the tongue who underwent surgery and intra-operative frozen section at our center from January 2007 to June 2010., Results: Frozen section was found to have very high accuracy in assessment of margin as well nodal status. On frozen section, 2% of our patients had positive margins and 21% had close margins. Most of these underwent intra-operative revision and at final pathology, 1.2% patients had positive margins and 11% were close. Of the 651 supraomohyoid neck dissections performed, one third were found to have occult metastases on frozen section. Of those reported positive on frozen section, 68% got additional removal of level 4 ± 5. Interestingly, 11% of these additionally removed nodes harbored metastases at final pathology. However, 7% of the patients were wrongly declared negative on frozen section. Tumor thickness was predictor of margin positivity as well as occult metastases. Tumor volume did not correlate with occult metastases or margin status., Conclusions: Frozen section nearly halves the rates of positive margin and close margins which certainly translates into clinical benefits. The incidence of 11% positive nodes in the frozen section guided removal of lower levels is an important finding in our study that questions the ability of supraomohyoid neck dissection to completely eradicate the nodal burden in such patients.

Background: MicroRNA (miRNA) expression is broadly altered in cancer, but few studies have investigated miRNA deregulation in oral squamous cell carcinoma (OSCC). Epigenetic mechanisms are involved in the regulation of >30 miRNA genes in a range of tissues, and we aimed to investigate this further in OSCC., Methods: TaqMan® qRT-PCR arrays and individual assays were used to profile miRNA expression in a panel of 25 tumors with matched adjacent tissues from patients with OSCC, and 8 control paired oral stroma and epithelium from healthy volunteers. Associated DNA methylation changes of candidate epigenetically deregulated miRNA genes were measured in the same samples using the MassArray® mass spectrometry platform. MiRNA expression and DNA methylation changes were also investigated in FACS sorted CD44(high) oral cancer stem cells from primary tumor samples (CSCs), and in oral rinse and saliva from 15 OSCC patients and 7 healthy volunteers., Results: MiRNA expression patterns were consistent in healthy oral epithelium and stroma, but broadly altered in both tumor and adjacent tissue from OSCC patients. MiR-375 is repressed and miR-127 activated in OSCC, and we confirm previous reports of miR-137 hypermethylation in oral cancer. The miR-200 s/miR-205 were epigenetically activated in tumors vs normal tissues, but repressed in the absence of DNA hypermethylation specifically in CD44(high) oral CSCs. Aberrant miR-375 and miR-200a expression and miR-200c-141 methylation could be detected in and distinguish OSCC patient oral rinse and saliva from healthy volunteers, suggesting a potential clinical application for OSCC specific miRNA signatures in oral fluids., Conclusions: MiRNA expression and DNA methylation changes are a common event in OSCC, and we suggest miR-375, miR-127, miR-137, the miR-200 family and miR-205 as promising candidates for future investigations. Although overall activated in OSCC, miR-200/miR-205 suppression in oral CSCs indicate that cell specific silencing of these miRNAs may drive tumor expansion and progression.

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Carcinoma of the uterine cervix is the most common female malignancy in the world. While cervical cancer is a worldwide disease, oral cancer has the highest incidence in developing countries, especially among tobacco and alcohol users and betel quid chewers. A strong association of cervical and oral cancer with high-risk human papillomavirus (HPV) 16 and 18 infections underlines the importance of the virus in the pathogenesis of these squamous cell carcinomas. Functionally high-risk HPV infection contributes to carcinogenesis and tumor progression predominantly through the actions of two viral oncogenes, E6 and E7. The E6 and E7 genes have been studied in different patient populations and a number of variants have been described. More than 40 variants have been classified and may be related to differences in progression of squamous intraepithelial lesions. The transcription factor, NFkappaB and its activation pathways are frequently targeted by viruses and aberrant constitutive activation of NFkappaB is frequently found in human tumors of diverse tissue origin. Diet-gene interactions are also likely to contribute considerably to the observed inter-individual variations in HPV associated cancer risk, in response to exposures to the nutritional factors that have the potential to promote or protect against cancer.

Background: Paclitaxel (24-hour infusion) has yielded activity in advanced squamous cell carcinoma of the head and neck (SCCHN). Protracted exposure to paclitaxel may overcome resistance observed by using shorter infusions. Therefore we sought to evaluate paclitaxel by 96-hour infusion in both treatment-naïve and previously treated patients with SCCHN., Materials and Methods: Eligibility stipulated bi-dimensionally measurable, biopsy-documented, incurable SCCHN, Eastern Cooperative Oncology Group performance status (PS) 0-1, and adequate physiological indices. Patients were divided into three cohorts: 1) chemotherapy-naïve; 2) chemotherapy-exposed, paclitaxel-naïve; and 3) chemotherapy and paclitaxel exposed. Paclitaxel was dosed at 140 mg/m2 (96-hour infusion) every 3 weeks in treatment-naïve patients and at 120 mg/m2 (96 hours) every 3 weeks in previously treated patients., Results: Fifty patients were accrued between February 1997 and July 2000. The study was terminated because of low response rate. Eighty percent of patients were male, 75% PS 1. Nearly half the patients had oropharyngeal or hypopharyngeal primary sites. There was one treatment-related death due to neutropenic fever/pneumonia. Grade 4 toxicities included granulocytopenia in eight patients (20%), thrombocytopenia, and stomatitis in one patient each. Grade 3 or greater anemia occurred in 10 patients. There was no grade 2 or 3 peripheral sensory neuropathy. In 15 chemotherapy-naïve patients, two responses (13%) were observed. There were no responses in treatment-exposed patients. The overall median survival was 5.5 months, and 1-year survival rate 10%. Treatment-naïve patients had a median survival of 8.2 months and 1-year survival rate of 20%., Conclusions: Paclitaxel by 96-hour infusion at a dose of 120-140 mg/m2/96 hours is only marginally active in the treatment of SCCHN. This dose and schedule cannot be recommended for further evaluation.

Objectives/hypothesis: Surgical excision is regarded as the treatment of choice for sinonasal inverted papilloma. Resection can be performed endoscopically or through an external approach. Debate exists about which approach to use. The study presents different endoscopic techniques for various tumor locations and reviews the results., Study Design: A prospective study and an integrated literature review., Methods: Seventeen consecutive patients with inverted papilloma who underwent endoscopic surgical excision, including medial maxillectomies and modified Lothrop procedures, were analyzed. Preoperative symptoms, computed tomography and magnetic resonance imaging findings, operative findings, tumor stage, and outcomes were recorded., Results: Thirteen male and four female patients presented with inverted papilloma between December 1993 and October 2001. Nasal obstruction was the most common presenting symptom (50%). Sixty-five percent of tumors were either stage II or stage III. Endoscopic resection was the primary treatment in 14 patients. Of the three patients who were secondarily treated endoscopically, one had recurrence and was subsequently found to have focus of squamous cell carcinoma. The overall recurrence rate was 6% and the incidence of malignancy was 6% (1 of 17). Recurrence rate for primary resections was zero (0 of 14). Five patients underwent endoscopic medial maxillectomies, and one patient with frontal sinus inverted papilloma was successfully treated with a modified endoscopic Lothrop procedure., Conclusions: Endoscopic sinus surgery is a viable treatment alternative for sinonasal inverted papilloma. Recurrence rates for primary treatment are comparable to external approaches. Close follow-up of patients is mandatory because recurrence may be associated with malignancy.

Background: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population., Methods: Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival., Results: Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%)., Conclusions: Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck., (Copyright 2002 American Cancer Society.)

Aims and Background: Altered oncogenic activity is a feature associated with many malignant and premalignant conditions. Among the many oncogenes, ras and myc are commonly altered in many tumors. This study aims to evaluate the expression of ras and c-myc oncoproteins in a total of 204 cervical tissue samples, including premalignant and malignant lesions as well as apparently normal cervical tissue., Methods and Study Design: Mouse monoclonal antibodies against the three mammalian ras gene products (c-H-ras, c-K-ras, c-N-ras) and the c-myc protein were used to evaluate oncoprotein expression by immunocytochemistry., Results: None of the samples analyzed displayed immunoreactivity for H-ras and K-ras. Normal cervical epithelium showed minimal immunoreactivity for N-ras with about 33% of the samples expressing the protein. More conspicuous expression in normal tissue was displayed by c-myc, with about 90% of the samples expressing the protein (mean value of cells positive=34%). The immunoreactivity for N-ras increased with increasing histological abnormality from low-grade squamous intraepithelial lesions (SIL) to invasive carcinoma. Increased immunoreactivity for N-ras was evident in the basaloid cells of malignant lesions, with the maximum value of 66% found in poorly differentiated squamous cell carcinoma (PDSCC). The percentage of nuclei positive for c-myc also showed a gradual increase from low-grade SIL onwards, the highest positivity being found in PDSCC, where the mean value was 85%. Statistical analysis revealed a good correlation between the expression of N-ras (r=0.8922, P=0.001) and c-myc (r=0.8856, P=0.001) and various histological stages of tumor progression in the cervical epithelium., Conclusions: These results therefore suggest that c-myc and N-ras oncoproteins are important during tumor progression in the uterine cervix.

The delay in the diagnosis of oral cancer has been variously reported as being contributed by the clinicians, patients or both. The purpose of this study was to evaluate the referral pattern of 65 patients eventually diagnosed as having oral squamous cell carcinoma. The results showed that 50% of the patients delayed seeking professional help for more than 3 months after being aware of the lesion. The majority of the patients consulted medical practitioners as the first source of help. The mean clinicians' and patients' delay were 10.3 weeks and 28.9 weeks respectively. Dental practitioners showed a tendency to refer more advanced lesions compared to the medical practitioners. The findings raise the concern that lack of patients' awareness, misdiagnosis by clinicians and late detection by dental practitioners prevail thus calling for urgent measures towards early detection of the disease.