Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

OBJECTIVES: The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. MATERIALS AND METHODS: Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. RESULTS: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. CONCLUSION: Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Risk Stratification in Oral Cancer: A Novel Approach.

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Anonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision-recall analysis and the Kaplan-Meier survival analysis. Results: Low-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials. Conclusion: Nomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients.

Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication.

BACKGROUND: Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well-established features like perineural invasion (PNI), differentiation, and lymphovascular-invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3-4). METHODS: Seven hundred and forty-two patients with T3-4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS). RESULTS: OS was adversely impacted by PNI (p = 0.046), LVI (p = 0.038), moderate/poor differentiation (p = 0.001), close/involved surgical margins (p = 0.002), pT (p = 0.034), and pN (p < 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42-4.90) for one adverse feature and HR 4.23 (CI 2.34-7.67) for ≥2. CONCLUSION: In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation.

Nodal yield and topography of nodal metastases from oral cavity squamous cell carcinoma - An audit of 1004 cases undergoing primary surgical resection.

OBJECTIVES: Nodal metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC). Detailed topographic study of metastasis can guide surgical and adjuvant radiation treatment protocols. METHODS: Retrospective analysis of distribution of nodal spread was done by auditing pathology records of 1004 patients who underwent primary surgical management at our center. RESULTS: The median nodal yield was 41 (range of 9-166) nodes, per patient. Metastasis was present in 42.9% patients, of which 52.3% demonstrated extranodal extension. Reclassification by AJCC8 criteria resulted in up-staging in 35.6% patients (pN1, pN2a, pN2b, pN2c, pN3a and pN3b in 13.1%, 3.7%, 6.9%, 0.9%, 0%, 18.1% respectively). Ipsilateral levels Ib and IIa were involved in a quarter of patients each, while IIb, IV and V were involved in < 4%, 3% and 1% of patients, respectively. Contralateral nodal metastasis was present in 5.4%. Skip metastases to level IV were 2.2% and 1.2% for tongue and gingivobuccal primaries. Tongue primaries had a lower likelihood of involving level Ib, but higher of level IIa and III, compared to gingivobuccal primaries, and a lower likelihood of extranodal extension. Primary site did not influence nodal metastasis to levels IIb, IV or V, but other factors like lymphovascular invasion, pT stage and margin status had an influence. CONCLUSION: This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.

Functional Landscape of Dysregulated MicroRNAs in Oral Squamous Cell Carcinoma: Clinical Implications.

MicroRNA (miRNA) dysregulation is associated with the pathogenesis of oral squamous cell carcinoma (OSCC), and its elucidation could potentially provide information on patient outcome. A growing body of translational research on miRNA biology is focusing on precision oncology, aiming to decode the miRNA regulatory network in the development and progression of cancer. Tissue-specific expression and stable presence in all body fluids are unique features of miRNAs, which could be potentially exploited in the clinical setting. Recent understanding of miRNA properties has led them to be useful, attractive, and potential tools either as biomarkers (distinct miRNA expression signature) for diagnosis and prognostic outcomes or as targets for novel therapeutic entities, enabling personalized treatment for OSCC. In this review, we discuss recent research on different aspects of alterations in miRNA profiles along with their clinical significance and strive to identify probable potential miRNA biomarkers for diagnosis and prognosis of OSCC. We also discuss the current understanding and scope of development of miRNA-based therapeutics against OSCC.