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Background: Lately SOX2 and SOX9, transcription factors associated with stemness-like phenotypes of cancer cells, have been linked to tumor growth, metastasis, and resistance to therapy., Methods: This study aimed on evaluating the expression of SOX2 and SOX9 in a large cohort of patients with OSCC including primary and recurrent tumors and corresponding lymph node metastases. Semiautomatic digital pathology scoring was used to determine protein expression and survival analysis was performed to evaluate its prognostic significance., Results: We found a significant downregulation of SOX9 from primary disease to lymph node metastases (p < 0.001). SOX9 expression and the subgroup SOX2 low SOX9 high were significantly correlated with worse overall survival (p < 0.05). Additionally, SOX2 low SOX9 high expression pattern was confirmed as independent prognosticator for overall survival., Conclusions: These results indicate the relevant role of SOX2 and SOX9 in patients with OSCC and show the clinical relevance for further investigation on the molecular mechanisms underlying SOX-related gene expression., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: This study aimed to explore the disparities in PD-1 and PD-L1 expression among oral squamous cell carcinomas (OSCCs) in individuals categorized as never-smokers/never-drinkers versus smokers/drinkers., Methods: Immunohistochemical staining for PD-1 and PD-L1, along with PDCD1LG2/cen9 dual color probe analysis, was conducted on 130 OSCC specimens from both smoker/drinker and never-smoker/never-drinker cohorts. Associations between smoking/drinking status, clinicopathologic data, immunohistochemical antibody expression, fluorescence in situ hybridization, and survival outcomes were assessed., Results: OSCC in never-smokers/never-drinkers exhibited significantly elevated PD-1 expression (p = 0.003), increased PD-L1-TPS expression (p = 0.044), and elevated PD-L1-CPS expression (p < 0.001). High PD-L1-ICS expression was more prevalent in never-smokers (p = 0.042). Moreover, never-smokers and never-drinkers demonstrated augmented PD-L1 gene copy numbers (p = 0.081 and p = 0.054, respectively). Increased PD-L1 gene copy number, particularly amplification, correlated with PD-L1-TPS (p = 0.039 and p < 0.001). Conversely, PD-L1 gene copy loss was associated with negative PD-L1-CPS (p = 0.023). Notably, positive PD-L1-CPS was significantly linked with improved overall survival (p = 0.023)., Conclusions: OSCC arising in never-smokers/never-drinkers exhibit heightened PD-1/PD-L1 signaling, suggesting potential efficacy of immune checkpoint therapy in this subgroup of tumors., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: Depth of invasion (DOI) has a significant clinical impact on the staging system of oral squamous cell carcinoma (OSCC). We aimed to compare the prognostic impact of treating DOI as a continuous variable rather than a categorical one., Methods: A retrospective review of 277 OSCC patients surgically treated in a tertiary care center from 2000 to 2020, with a minimum 2-year follow-up. The analyses were performed using Cox and logistic regression., Results: DOI as a continuous variable significantly predicted mortality in both univariate (p < 0.001) and multivariate (p < 0.001) analyses. It was also a significant predictor of locoregional recurrence (multivariate p = 0.039) and occult lymph node metastasis (univariate p = 0.005, multivariate p = 0.04). Categorical analysis failed to demonstrate the same significance., Conclusions: DOI as a continuous factor rather than a categorical one is significantly associated with mortality, locoregional recurrence, and occult lymph node metastasis. This innovative approach promotes personalized risk stratification and better decision-making., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

This systematic review and meta-analysis investigated the impact of salvage surgery on 5-year overall survival (OS) and prognostic factors in recurrent oral cavity cancer (rOCC) patients. Relevant literature before May 2022 was reviewed, including retrospective cohort studies and observational studies comparing salvage surgery to other treatments. Risk-of-bias assessments were conducted using the Newcastle-Ottawa scale. Statistical and subgroup analyses assessed the impact of salvage surgery on 5-year OS and prognostic factors. 3036 documents were initially retrieved, with 14 retrospective cohort studies (2069 participants) included. Meta-analysis of 5-year OS in salvage surgery patients yielded a rate of 43.0%. Subgroup analysis showed higher OS in Asians (49.9% vs. 36.9%, p = 0.003) and late-relapse (63.8% vs. 30.0%, p = 0.004) groups. Prognostic factors revealed hazards associated with nodal recurrence, extranodal extension, and perineural invasion. Salvage surgery is a viable option for rOCC patients, showing favorable 5-year OS outcomes. Low publication bias enhances study reliability, but its single-arm design limits conclusions on salvage surgery superiority over other treatments., (© 2024 Wiley Periodicals LLC.)

Objectives: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival., Methods: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review., Results: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors., Conclusions: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar., (© 2024 Wiley Periodicals LLC.)

Background: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC)., Methods: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable., Results: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58)., Conclusion: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery., Methods: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome., Results: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93)., Conclusions: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers., Methods: Retrospective data of 116 patients treated with a daily dose of 3.6-3.7 Gy in four fractions over 4 days to a total of three courses, with a 2-week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer., Results: Ninety-nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression-free survival were 12 months (95% confidence interval [CI]: 8-20) and 8 months (95% CI: 6-10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on-treatment hospitalization or grade 3-4 toxicities., Conclusion: The modified QUAD SHOT regimen is practical for palliation in head and neck cancers., (© 2024 Wiley Periodicals LLC.)

Objective: The aim was to research ACTL6A's role in oral squamous cell carcinoma (OSCC)., Methods: OSCC and normal samples were obtained from patients and public databases. GSEA was performed. CIBERSORT was utilized to analyze immune landscape. Kaplan-Meier survival analysis and multivariate Cox regression analysis were conducted. After knocking down ACTL6A, we performed MTT assay, transwell assays, and flow cytometry to detect the impact of knockdown., Results: ACTL6A expressed higher in OSCC samples than normal samples. The CNV and mutation rate of TP53 was higher in ACTL6A high-expression group. TFs E2F7 and TP63 and miRNA hsa-mir-381 were significantly related to ACTL6A. ACTL6A could influence immune microenvironment of OSCC. Knockdown of ACTL6A inhibited OSCC cells' proliferation, migration, and invasion. ACTL6A was able to predict OSCC prognosis independently., Conclusion: ACTL6A expressed higher in OSCC than normal samples and it could be used as an independent prognostic marker in OSCC patients., (© 2024 Wiley Periodicals LLC.)

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: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received., Methods: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers., Results: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID-19. The patients who received treatment and got affected with COVID-19 had a far worse impact and higher mortality rate than all other groups., Conclusion: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID-19, is an advisable strategy based on this model., (© 2020 Wiley Periodicals, Inc.)

Background: American Society of Clinical Oncology guidelines recommend that the decision to give postoperative radiotherapy (PORT) for pN1 oral cavity squamous cell carcinoma (OCSCC) without other adverse features be based on the adequacy of the neck dissection (<18 or ≥18 nodes)., Methods: We conducted a cohort study of the National Cancer Database examining how PORT affects survival. We stratified analyses by the adequacy of the neck dissection and lymph node (LN) size., Results: Our cohort comprised 1909 patients (898 received PORT). PORT conferred a survival benefit in the overall cohort (adjusted hazard ratio 0.82, 95% CI 0.72-0.94). There was similar benefit in patients receiving inadequate and adequate neck dissections. Patients with >10 mm LN metastasis derived greater benefit compared with patients with smaller metastases., Conclusions: In pN1 OCSCC without other adverse features, the size of the LN metastases may predict benefit from PORT, whereas the adequacy of the neck dissection may not., (© 2019 Wiley Periodicals, Inc.)

Objectives: Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE)., Materials and Methods: Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1995 and 2018 were performed, with local failure (LF) and disease-specific mortality (DSS) as the primary endpoints., Results: After adjusting for other adverse histopathological factors and adjuvant therapy, multifocal PNI was associated with a greater risk of LF (P = .01) and DSS (P = 0.02) compared to DOI. The effect of multifocal PNI was comparable to the effect of nodal metastases without ENE (P = 0.02). LF and DSS were not improved by the administration of adjuvant radiotherapy within unifocal or multifocal PNI groups., Conclusion: Multifocal PNI is associated with a greater risk of death in OSCC than DOI. Its effect is comparable to that of nodal metastases (without ENE)., (© 2019 Wiley Periodicals, Inc.)

Background: We aimed to determine the patterns of local recurrence after curative resection and reconstruction for oropharyngeal and oral cancers., Methods: One hundred-fourteen patients with oropharyngeal and oral cancers underwent resection and reconstruction. The local recurrences were classified as "intra-flap" (the recurrent tumor was located in the flap tissue), "marginal" (≤5 mm from the flap anastomosis), and "outside" (in the original tissue and >5 mm from the anastomosis) recurrences., Results: Twenty-seven patients (23.7%) experienced local recurrence, while 32 (28.1%) experienced regional, and nine (7.9%) recurred distantly. Among those who showed local recurrence, one developed "outside" recurrence and the remaining 26 developed "marginal" recurrences. Age >60 years and lymph node metastasis were associated with poor disease-free survival and overall survival (OS), while the perineural invasion was related to poor locoregional failure-free survival and OS., Conclusion: Most recurrences developed at the anastomosis marginal site, while none developed in the flap tissue., (© 2019 Wiley Periodicals, Inc.)

Background: We ascertain the association of postoperative infection on survival in patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC)., Methods: A retrospective study of patients with stage III/IVA OCSCC undergoing curative-intent surgery was performed. Postoperative infection was considered within 30 days after surgery. Kaplan-Meier survival curves were used to compare overall survival (OS) in patients with postoperative infection. Cox regression and propensity-score matching were used to adjust for confounders., Results: Fifty-four of 114 patients had a postoperative infection. The 5-year OS in patients with a postoperative infection (24.1%) was lower than those without (65.2%; P < .0001). Postoperative infection was a negative predictor of OS after adjusting for patient, antibiotic, pathologic, and operative factors; the adjusted hazard ratio for OS was 2.54 (95% confidence interval, 1.27-5.09)., Conclusion: Postoperative infection is a strong negative predictor of OS in patients with OCSCC undergoing ablative surgery., (© 2019 Wiley Periodicals, Inc.)

Background: Early oral cavity cancer has good prognosis but recurrence in them is still not uncommon. There is no general consensus on the prognostic factors and adjuvant therapy that would have a significant impact on survival., Methods: A retrospective analysis of early oral cavity cancer patients during the time period 2009-2017. The data regarding demographics, histopathological features, and recurrence patterns were collected and analyzed., Results: Depth of invasion (DOI) was the most important prognostic factor among all the factors analyzed. Further analysis showed that addition of adjuvant radiotherapy for patients with DOI >5 mm did not show survival benefits (P = .73). Another subset analysis of patients with DOI >10 mm also did not show any survival advantage with adjuvant therapy P = .24., Conclusion: There is no benefit of adding adjuvant RT in patients with DOI > 5 mm or in patients who were upstaged to T3 based only on DOI., (© 2019 Wiley Periodicals, Inc.)

Background: To explore the clinicopathological significance of tumor budding (TB) on oral squamous cell carcinoma (OSCC) prognosis., Methods: Data of 200 patients with OSCC were retrieved from the cancer registration database in Taipei Veterans General Hospital. Clinicopathological characteristics and survival relevant to TB were analyzed., Results: The data showed that TB was predominant in the tongue and floor of the mouth in younger patients with OSCC and correlated with several pathological factors, such as perineural invasion and lymphovascular invasion. Patients with TB have significantly lower recurrence-free survival (P ≤ .0001). TB was significantly associated with lymph node metastasis in patients with early cancer stage (P = .042). Multivariate analysis demonstrated extranodal extension and TB as independent predictors of lymph node recurrence (adjusted hazard ratio = 9.90 and 3.89, respectively)., Conclusion: TB is a significant predictor of tumor aggression with locoregional failure even in the revised 8th American Joint Committee on Cancer staging system., (© 2019 Wiley Periodicals, Inc.)

Background: The aim of the present study was to assess the long noncoding RNA (lncRNA) expression profile of oral cancer and clarify the biological functions and clinical value of a novel lncRNA ENST00000470447.1., Method: Microarray assay was used to explore lncRNA expression profiles in three paired oral cancer and adjacent normal tissue samples. The expression of targeted lncRNA (ENST00000545372.1, ENST00000470447.1, and ENST00000412353.1) was validated by quantitative real-time polymerase chain reaction. Then we evaluated the biological and clinical roles of ENST00000470447.1 in oral cancer by in vitro assays and multivariable Cox regression analysis., Results: LncRNAs were aberrantly expressed in oral cancer tissues. The expression levels of ENST00000470447.1 and ENST00000412353.1 in oral cancer tissues were significantly lower than those in matched adjacent noncancerous tissues (P < .001). in vitro assays indicated that overexpression of ENST00000470447.1 significantly inhibited the proliferation, migration, and invasion ability of Tca-8113 cells, whereas promoted the apoptosis of Tca-8113 cells. Furthermore, ENST00000470447.1 expression was significantly correlated with tumor differentiation (P = .030). Cox regression analyses demonstrated that high ENST00000470447.1 expression was associated with better disease-free survival for patients with oral cancer (hazard ratio: 0.25, 95% CI: 0.06-0.95; P = .041)., Conclusion: Our findings suggest that ENST00000470447.1 can be served as a potential novel marker for recurrence and metastasis prediction of patients with oral cancer, which may provide a potential therapeutic target for oral cancer., (© 2019 Wiley Periodicals, Inc.)

Background: The purpose of this analysis is to evaluate whether postoperative radiotherapy (PORT) at the same facility as surgery portends to better survival outcomes compared to PORT given at a different facility., Methods: Patients underwent upfront surgery at the National Cancer Database reporting facility followed by PORT. PORT was coded as performed at either the same facility or at a different facility as surgery., Results: A total of 10 832 patients were selected. Five-year overall survival (OS) was higher in patients undergoing PORT at the same facility: 52.5% vs 48.4% (P < 0.001). PORT performed at the same facility was associated with improved OS under multivariate (HR, 0.92; P = 0.01) and propensity score matched (hazard ratio, 0.90; P = 0.004) analyses., Conclusions: OS was better among patients with head and neck cancer who received PORT at the same facility as surgery., (© 2019 Wiley Periodicals, Inc.)

Background: This study's aim was to identify CD68 and stabilin-1 expressions and their prognostic implications in patients with oral cavity cancer (OCC)., Methods: Stabilin-1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin-1 expression levels and their effect on prognostic factors and survival., Results: Fifty-four patients' data were analyzed. CD68 and stabilin-1 expressions were positively correlated (P = .008). CD68 and stabilin-1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin-1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence-free nor OCC-specific survival., Conclusion: CD68 and stabilin-1 expressions in OCC were positively correlated. Stabilin-1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed., (© 2019 Wiley Periodicals, Inc.)

Background: The purpose of this study was to retrospectively describe the characteristics and outcomes of patients with oral squamous cell carcinoma and level IV/V metastasis and to compare patients who underwent no postoperative therapy with those who underwent postoperative radiotherapy (RT) and concomitant chemoradiotherapy (CCRT)., Methods: We evaluated 669 patients. Clinicopathological data, postoperative therapy, and clinical course were investigated., Results: Sixty-one patients (9.1%) developed level IV/V metastasis. The 3-year cumulative overall survival rates of patients with and without level IV/V metastasis were 47.3% and 64.3%, respectively. Tongue tumors, pN2 or N3 classification, and moderate or poor differentiation were significantly associated with the development of level IV/V metastasis. The surgery+RT/CCRT group was associated with better 3-year cumulative disease-specific survival and overall survival rates than the surgery only group., Conclusion: Adjuvant therapy (RT alone or CCRT) after surgery is recommended for patients with level IV/V metastasis., (© 2019 Wiley Periodicals, Inc.)

Background: The associations between malignant transformation of oral potentially malignant disorders (OPMDs), oral cancer development and prognosis, and apurinic/apyrimidinic endonuclease 1 (APE1) functional polymorphisms are unclear., Methods: Patients with OPMDs, patients with oral cancer, and healthy controls from the community were recruited to determine the effects of APE1 polymorphisms on malignant transformation, overall survival, and genetic susceptibility, respectively., Results: The APE1 Asp148Glu polymorphisms significantly correlated with a high hazard ratio for OPMD malignant transformation (adjusted hazard ratio [AHR] = 2.29; 95% confidence interval [CI] = 1.44-3.74) and low overall survival in oral cancer patients (AHR = 1.71, 95% CI = 1.11-2.56) according to follow-up and survival analysis. However, APE1 polymorphisms did not significantly correlate with development of oral cancer in the case-control study and logistic regression analysis., Conclusions: These results indicate that APE1 Asp148Glu polymorphisms may have indirect roles in increasing the OPMD malignant transformation rate and in decreasing overall survival in oral cancer patients., (© 2019 Wiley Periodicals, Inc.)

Background: This study evaluated carbon-ion radiotherapy (C-ion RT) for oral non-squamous cell carcinomas (non-SCC)., Methods: We retrospectively obtained data from 74 patients who underwent C-ion RT for oral malignancies between April 1997 and March 2016. The C-ion RT was administered in 16 fractions at a total dose of 57.6 or 64.0 Gy (relative biological effectiveness)., Results: Forty-three patients had salivary gland carcinomas, 29 patients had mucosal melanoma, and 2 patients had other types of pathologies. The tumors were classified as T1-T3 (24 cases), T4a (21 cases), or T4b (29 cases). The median follow-up was 49 months. The 5-year rates were 78.8% for local control, 36.2% for progression-free survival, and 58.3% for overall survival. Although 10 patients developed grade 3 osteoradionecrosis after C-ion RT, all patients maintained their mastication and deglutition functions after sequestrectomy and prosthesis placement., Conclusion: C-ion RT was effective for oral non-SCC and had acceptable toxicities., (© 2019 The Authors. Head & Neck published by Wiley Periodicals, Inc.)

Background: This study evaluated the prognostic role of Fluorine 18-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG PET/CT) parameters quantitatively measured in patients with recurrent oral cavity cancer., Methods: Cox proportional hazards regression analyses were used to assess the associations between quantitative 18 F-FDG PET/CT parameters and other clinicopathological factors and progression-free survival (PFS) and overall survival (OS)., Results: All of the 18 F-FDG PET parameters (SUV max , SUV mean , SUV peak , metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were significantly associated with poor PFS and OS outcomes after salvage treatment (P < .01). In multivariate analyses, Karnofsky performance score, recurrence site, MTV, and TLG were independent variables predictive of both PFS and OS (P < .05). High MTV (>8.8 mL) or TLG (>29.4 g) values at recurrent lesions were associated with >5-fold increased risk for tumor progression and mortality after salvage surgery., Conclusions: The PET parameters of MTV and TLG measured at recurrent lesions may predict tumor progression and survival after salvage treatment., Condensed Abstract: This study examined the role of 18 F-FDG PET/CT at recurrent staging for predicting tumor progression and survival in 71 consecutive patients with recurrent oral cavity squamous cell carcinomas. Of 18 F-FDG parameters, metabolic tumor volume and total lesion glycolysis were independent factors predictive of tumor progression and survival after salvage treatment., (© 2019 Wiley Periodicals, Inc.)

Background: The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab-based sequential therapy as a primary treatment., Methods: Forty-seven treatment-naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab-based radiotherapy. Immunohistochemical staining was applied to study the tissues., Results: The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression-free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty-two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD-L1 staining compared to pretreatment biopsy in the post hoc study., Conclusion: The regimen was effective in selected patients. Increased PD-L1 suggested altered tumor features., (© 2019 Wiley Periodicals, Inc.)

Background: To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer., Methods: A total of 27 717 oral cancers mainly from a population-based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012., Results: Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92-2.51) for tongue, 2.60 (2.28-2.97) for buccal, 2.68 (2.20-3.28) for floor of mouth, 2.96 (2.52-3.47) for hard palate, 6.04 (5.17-7.05) for gingiva, and 10.83 (9.20-12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31-1.67) in buccal, 1.61 (1.43-1.82) in tongue, 1.68 (1.41-1.99) in floor of mouth, 1.79 (1.57-2.05) in gingiva, 1.97 (1.71-2.26) in hard palate, and 2.15 (1.89-2.45) in oropharynx., Conclusion: Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance., (© 2019 Wiley Periodicals, Inc.)

Background: To evaluate the prognostic value of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in oral, pharyngeal, and lip cancer for survival and relapse., Methods: Clinic-pathologic and hematological records were retrospectively retrieved. Patients completed follow-up period were included for survival and relapse analysis., Results: The preoperative NLR value was a prognostic factor for both overall survival and relapse-free survival. The high NLR group demonstrated higher total relapse rate, higher local relapse rate, and higher relapse rate within 12 months. However, the preoperative PLR did not associate with survival or relapse., Conclusions: The preoperative NLR, not PLR, is an independent prognostic indicator of survival. It also exhibits predictive value for relapse, particularly early relapse within 12 months. The preoperative NLR value might be recommended as a useful tool for predicting the outcomes and stratifying patients for different management strategies., (© 2019 Wiley Periodicals, Inc.)

Background: This article is about the eighth edition staging guidelines for upstaged patients with oral cavity squamous cell carcinoma (OCSCC) with >10 mm depth to pT3. This upstages some patients from stage I-II to stage III, a point at which patients are traditionally considered for postoperative radiation therapy (PORT). The role of PORT in patients upstaged for >10 mm depth is unknown., Methods: We identified patients with surgically resected stage I-II OCSCC with >10 mm depth who were upstaged to stage III. We used Cox proportional hazard modeling to compare patients who received PORT to those who did not (median follow-up 38.6 months)., Results: We observed that 3.6% of patients with OCSCC were upstaged to stage III for depth >10 mm including 823 eligible patients. On adjusted analyses, PORT was associated with improved overall survival in patients upstaged to stage III (adjusted hazard ratio [aHR] 0.47, 95% confidence interval [CI] 0.30-0.73)., Conclusion: PORT is associated with improved survival for patients with OCSCC upstaged to stage III for >10 mm depth., (© 2019 Wiley Periodicals, Inc.)

Background: To develop and validate practical prognostic indexes (PIs) for predicting the prognosis and response to postoperative adjuvant therapy in patients with oral squamous cell carcinoma (OSCC)., Methods: A large cohort of 1071 OSCC patients were randomized to either training set (N = 708) or validation set (N = 363). Three types of PIs were developed according to the nomogram scores, β coefficients and excess hazard ratios, respectively. Restricted cubic spline was used to demonstrate the relationship between PIs and the risks of death., Results: First, a nomogram was developed incorporating age at diagnosis, smoking status, clinical stage, tumor differentiation, lymph node status, comorbidity, and neutrophil to lymphocyte ratio levels. Then, three PIs were established with high survival predictive ability, and were superior to AJCC staging system (all P < .05). The risks of death were escalated continuously with the increasing number of PIs. Interestingly, adjuvant chemoradiotherapy was positively associated with poor overall survival in patients with low PIs, but exerted a beneficial effect on patients with high PIs., Conclusion: Combined nomogram with further established PIs not only predicts the survival probability of OSCC patients, but also continuously quantifies the risk of death. High PIs could predict a beneficial response to adjuvant chemoradiotherapy, whereas low PIs indicate an unfavorable response., (© 2018 Wiley Periodicals, Inc.)

Background: Oral tongue/floor of mouth squamous cell carcinoma (OTFMSCC) with a depth of invasion (DOI) > 10 mm involves extrinsic muscles and lingual neurovascular/lymphatic bundles. "Compartmental" hemiglossopelvectomy (CHGP) was developed to improve loco-regional control by "en bloc" removal of tumor and its pathways of spread., Methods: We conducted a retrospective observational study on 45 CHGPs performed at a single institution for OTFMSCC with a DOI > 10 mm at CT/MR. Group A (n = 35) included naïve patients, and group B (n = 10) recurrent cancers. We evaluated 2-year overall survival (OS), disease-free survival (DFS), local control (LC), and loco-regional control (LRC)., Results: Two-year OS, DFS, LC, and LRC were 80%, 91%, 100%, and 94% for group A, and 27%, 26%, 67%, and 36% for group B, respectively. Salvage surgery and positive margins were significantly associated with worse prognosis., Conclusion: CHGP is a reliable oncologic approach in primary surgery for advanced OTFMSCC. In recurrent cancers, survival remains poor., (© 2018 Wiley Periodicals, Inc.)

Background: Cortactin (CTTN) is located on chromosome 11q13 and is associated with invasiveness in various cancer entities. CTTN protein expression could be a prognosticator of oral squamous cell carcinoma (OSCC) in terms of recurrence and survival., Methods: CTTN-dependent invasion was performed using migration assay in human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) cells. Cortactin protein analysis in tissue microarrays was used for correlation with clinical parameters, as well as for survival analysis. Gene expression profiling in HNSCC cells was performed to unreveal CTTN signaling., Results: Knockdown of CTTN in HNSCC cells showed less invasion in vitro. Gene expression profiling showed various deregulated genes known to be involved in progression. We confirmed the link between CTTN overexpression and progression in a large clinical cohort. High expression was associated with worse overall and progression-free survival., Conclusions: We propose CTTN for managing OSCC in terms of adjuvant therapy and aftercare. Furthermore, our study reveals new potential targets in CTTN signaling for individualized OSCC therapy., (© 2018 Wiley Periodicals, Inc.)

Background: Aldo-keto reductase family 1 member B10 (AKR1B10) expression in oral squamous cell carcinoma (OSCC) tissue specimens is correlated with the progression and prognosis of OSCC., Methods: Saliva samples were obtained from 35 normal controls and 86 patients with OSCC before cancer surgery. The AKR1B10 levels were determined using enzyme-linked immunosorbent assay (ELISA)., Results: The mean salivary AKR1B10 levels were significantly higher in the patients with OSCC than in the normal controls (P < .001). Higher salivary AKR1B10 levels were significantly associated with larger tumor size, more advanced clinical stage, and areca quid chewing habit. Patients with OSCC with a higher salivary AKR1B10 level (>646 pg/mL) had a significantly poorer survival than those with a lower (≤646 pg/mL) salivary AKR1B10 level (P = .026)., Conclusion: The salivary AKR1B10 level may be a promising biomarker for screening high-risk patients with OSCC and monitoring the progression of OSCC., (© 2018 Wiley Periodicals, Inc.)

Background: Definitive surgery is recommended for oral cavity squamous cell carcinoma (SCC). The purpose of this study was to present our assessment of the disparities in treatment selection for oral cavity SCC., Methods: Non-Hispanic white and non-Hispanic black patients with oral cavity SCC were identified in the National Cancer Database (NCDB). Regression models were used to estimate relative risk (RR) of receiving surgery and absolute difference between non-Hispanic white and non-Hispanic black patients., Results: There were 82.3% of non-Hispanic white patients who received surgery, compared to 64.2% of non-Hispanic black patients (P < .001). The non-Hispanic black patients were less likely to receive surgery than non-Hispanic white patients (RR 0.87) with an absolute difference of 10.9%. The non-Hispanic black patients were significantly more likely to not be offered surgery (RR 1.42) and to refuse recommended surgery (RR 1.38) but not have a contraindication to surgery (RR 1.17)., Conclusion: The non-Hispanic black patients are less likely to receive or be recommended surgery for oral cavity SCC and are more likely to refuse surgery. Further study is needed to identify strategies to close this disparity., (© 2018 Wiley Periodicals, Inc.)

Background: The treatment failure for oral squamous cell carcinoma (SCC) frequently takes the form of local and regional recurrences. We investigated the role of lingual lymph nodes (LLNs) in the recurrence of SCC of the tongue and the floor of the mouth., Methods: A total of 111 patients with SCC of the tongue and the floor of the mouth who received treatment between 2012 and 2017 were included in this study. The patients with lingual lymph nodes that were confirmed to be metastasis on pathological examination were classified into the LNN group. The demographic and clinical data differences between the No-LLN group and the LLN group were compared. Statistical analyses were performed using the Pearson chi-square test RESULTS: The total incidence of LLNs was 17.12% (19/111) and 5 patients (4.5%) demonstrated LLN metastases. All the patients with LLN metastases had a neck lymph node status of N2 classification. The incidence and metastasis of the LLNs were associated with pathological classifications of SCC of the tongue and the floor of the mouth., Conclusions: LLNs are rare in patients with SCC of the tongue and the floor of the mouth, and they would be ready to be omitted. The dissection of these LLNs would be of benefit to those patients with advanced pathological grade., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of our article was to describe a tertiary center's experience with patients with primarily surgically treated early-stage intraoral cancer with a second primary malignancy confirmed during follow-up., Methods: A total of 183 patients were primarily surgically treated for oral cancer between 2000 and 2004. Among these, 24 patients (13.1% (24/183)) met inclusion criteria., Results: There were 22 men (91.7%) and 2 women (8.3%) with a median age of 59.5 years. Patients with head and neck cancer with a second primary malignancy had significantly higher survival compared to nonhead and neck cancer with a second primary malignancy. Patients with head and neck cancer with second primary malignancy were diagnosed during the period of 14 to 45 months (median 29 months), whereas nonhead and neck cancer with second primary malignancy occurred in a period of 7 to 46 months (median 19 months)., Conclusion: This study highlights the importance of optimizing screening strategies for second primary malignancies. In order to improve the survival of patients with head and neck squamous cell carcinoma (HNSCC), effective programs of screening and/or chemoprevention of second primary malignancies are essential., (© 2018 Wiley Periodicals, Inc.)

Background: This study analyzed the expression of CD44 and cystine-glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival., Methods: Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS)., Results: Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P < .05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P < .01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P < .05 each)., Conclusion: Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC., (© 2018 Wiley Periodicals, Inc.)

Background: The American Joint Committee on Cancer (AJCC) eighth edition has incorporated depth of invasion into TNM classification of oral cavity squamous cell carcinoma (SCC) due to the prognostic impact on recurrence and survival. After reclassifying our patients with T1 to T2 oral cavity SCC according to these recommendations, we intended to study the effect of adverse pathological features (perineural invasion [PNI], lymphovascular invasion, and differentiation) on overall survival (OS)., Methods: We conducted a retrospective analysis of 442 patients with T1 to T2 oral cavity SCC. Univariate and multivariate analysis was performed for impact of adverse pathological features on OS., Results: For the newly reclassified T1 to T2 oral cavity tumors, on multivariate analysis, the prognostically relevant parameters were PNI (P = .032) and differentiation (P = .009). Increasing adverse pathological features resulted in worse survival (P = .005)., Conclusion: Incorporation of PNI and differentiation better reflect prognostic outcome in oral cavity tumors classified as T1 to T2 as per the new AJCC eighth edition. Increasing adverse pathological features resulted in worse survival., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to determine the impact of adjuvant radiotherapy (RT) in locoregionally advanced oral cavity cancer., Methods: Data were extracted from the National Cancer Data Base, of which overall survival (OS) is the only outcome variable available. The chi-square test and Cox regression models were used., Results: A total of 6654 patients were identified. The utilization of adjuvant RT has increased over time. A propensity matched cohort included 3946 patients, exactly one-half of whom received adjuvant RT. Independent predictors associated with receipt of adjuvant RT included age, Charlson/Deyo comorbidity score, extracapsular extension, surgical margins, and T and N classifications. On multivariable analysis, adjuvant RT remained an independent prognosticator for OS., Conclusion: Receipt of adjuvant RT is a prognostic factor associated with improved OS, its utilization has increased over time, and it should be considered for clinically suitable patients who have undergone resection for the disease., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression., Methods: The KPNA2 expressions were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2-knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real-time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor-kappa B (NF-κB)., Results: The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease-specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)-1β-induced nuclear import of NF-κB and MMP (MMP-1, MMP-3, and MMP-9) transcription., Conclusion: The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP-mediated metastasis., (© 2018 Wiley Periodicals, Inc.)

Background: Overexpression of keratin 17 (K17) is highly associated with poor prognosis in squamous cell carcinoma (SCC) of the cervix. This study was performed to (1) determine whether K17 may be a prognostic biomarker in head and neck squamous cell carcinoma (HNSCC) and (2) to establish if K17 expression is associated with human papillomavirus (HPV) status., Methods: Immunohistochemical staining was performed for K17 of oral, oropharyngeal, and laryngeal SCCs, and normal oropharyngeal mucosa. The HPV status was determined using polymerase chain reaction (PCR)., Results: Elevated K17 expression was significantly associated with an overall decreased patient survival (P = .02) and, more specifically, in patients with oropharyngeal SCC (P = .01). When controlling for HPV status and tumor location K17 was still a significant predictor of survival (P = .01)., Conclusion: Therefore, K17 is a novel prognostic biomarker of poor survival for patients with HNSCCs, controlling for anatomic site and HPV status., (© 2018 Wiley Periodicals, Inc.)

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: Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC)., Methods: Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy., Results: There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases)., Conclusion: Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications., (© 2018 Wiley Periodicals, Inc.)

Background: There is no published study on the influence of lymph node ratio on locoregional recurrence of squamous cell carcinoma (SCC) of the buccal mucosa. Therefore, we focused in our study on this specific anatomic subsite., Methods: We conducted a retrospective chart review of 95 patients from 2003-2013 with treatment-naive SCC of the buccal mucosa. Exclusion criteria were neoadjuvant chemoradiotherapy, perioperative death, N3 disease, unresectable disease, synchronous malignancy, and follow-up <3 months. Statistical analysis was performed using univariate and multivariate analysis., Results: Significant correlations were found between locoregional recurrence and pathologic N classification (P < .001), grading (P = .001), and lymph node ratio (P < .001). Multivariate analysis indicated lymph node ratio as an independent risk factor for locoregional recurrence (P = .002). A cutoff value under 7% led to a 10.383-fold higher risk of incurring a locoregional recurrence., Conclusion: Lymph node ratio is a useful parameter to stratify the risk of locoregional recurrence in patients with SCC of the buccal mucosa., (© 2017 Wiley Periodicals, Inc.)

Background: Intraoperative analysis of lymph nodes during a sentinel lymph node biopsy (SLNB) procedure could result in one-step surgery for early oral squamous cell carcinoma (OSCC) with an occult nodal metastasis. One-step nucleic acid amplification rapidly detects cytokeratin 19 (CK19) RNA with high accuracy. Sensitivity and specificity of CK19 expression in OSCC was evaluated., Methods: Immunohistochemical CK19 expression was done in 207 patients with OSCC with 65 cases of paired nodal metastases., Results: CK19 was expressed in 65% of all OSCC and even less in early OSCC (56%), with poor correlation between primary tumor and (occult) nodal metastasis. Furthermore, ectopic glandular tissue in close proximity of lymph nodes showed strong CK19 expression., Conclusion: CK19 lacks both sensitivity and specificity as a biomarker for nodal metastasis in OSCC, which questions the suitability for CK19-based one-step nucleic acid amplification in SLNB procedures. Therefore, future studies should focus on other biomarkers, because the concept of fast intraoperative diagnostics during SLNB remains attractive., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to investigate the clinical relevance of phosphorylated ribosomal protein S6 (p-S6), a surrogate marker of mammalian target of rapamycin (mTOR) activation, and p21 in a series of 125 patients with oral squamous cell carcinomas (OSCCs)., Methods: Immunohistochemical analysis was performed to ascertain the phosphorylation status of p-S6 at Ser235/236 and Ser240/244, p21, and p53 protein expression., Results: Expression of phosphorylated S6 protein on either serine 235/236 or serine 240/244 was detected in 83% and 88% tumors, respectively, and both of them were inversely and significantly correlated with the tumor size and local infiltration. Positive p21 expression was found in 91.5% of the cases, and was inversely correlated with tumor size. In OSCC, p21 expression correlates with p-S6 levels, a surrogate marker of mTOR activation, independently of p53 status., Conclusion: Expression of both p21 and p-S6 was found to inversely associate with tumor size but not survival outcomes in patients with OSCC., (© 2017 Wiley Periodicals, Inc.)

Background: Inoperable oral cavity squamous cell carcinoma (SCC) is a highly invasive disease associated with the extensive destruction of locoregional tissues and a dismal prognosis. Management strategies for these patients are limited., Methods: This study was a single arm, prospective, open-label phase II trial. A regimen consisting of cetuximab-docetaxel, cisplatin, and fluorouracil (C-TPF) followed by bio-chemoradiotherapy (bio-CRT) with cisplatin and cetuximab was administered to patients who responded to induction chemotherapy. The objective response rate to C-TPF was the primary endpoint., Results: Forty-three patients were enrolled in this study. The objective response rate of C-TPF was 88.4%; 88.9% (32/36) of the responders completed the full bio-CRT course, and the objective response rate of bio-CRT was 64.7%. The most common grade 3/4 adverse events for induction chemotherapy were leucopenia (32.6%) and febrile neutropenia (14.0%). The 1-year progression-free survival (PFS) and overall survival (OS) rates were 43% and 68%, respectively., Conclusion: C-TPF is an effective and tolerable induction chemotherapy regimen for inoperable oral cavity SCC., (© 2017 Wiley Periodicals, Inc.)

Background: Aldo-keto reductase family 1 member B10 (AKR1B10) is implicated in xenobiotic detoxification and has disparate functions in tumorigenesis that are dependent on the cell types. The purpose of this study was to investigate the clinicopathological significance of AKR1B10 as a prognostic marker for oral squamous cell carcinomas (OSCCs)., Methods: AKR1B10 protein expression was analyzed by immunohistochemistry in 77 patients with OSCC., Results: The AKR1B10 labeling score for OSCCs (1.16 ± 1.14) was significantly higher than that for normal oral mucosa (0.10 ± 0.23; p < .0001). High expression of AKR1B10 significantly correlated with large tumor size (p = .041), advanced TNM classification (p = .037), and patient's areca quid chewing habit (p = .025). Multivariate analysis revealed that high AKR1B10 labeling score >1.16 (hazard ratio, 3.647; p = .001) significantly correlated with mortality., Conclusion: AKR1B10 overexpression is an independent poor prognostic biomarker for OSCC. AKR1B10 inhibitors may be promising in clinical trials against OSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1327-1332, 2017., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to determine the effect of postoperative radiotherapy (PORT) on recurrence and survival in patients with oral squamous cell carcinoma (OSCC) of intermediate recurrence risk., Methods: Intermediate risk patients, defined as pT1, pT2, pN0, or pN1 with at least one adverse pathological feature (eg, lymphovascular/perineural invasion), were identified from the head and neck databases of the Liverpool Head and Neck Cancer Unit and the Sydney Head and Neck Cancer Institute. Patients who received surgery and PORT were case matched with patients treated by surgery alone based on pN, pT, margins, and pathological features., Results: Ninety patients were matched into 45 pairs. There was significant improvement (P = .039) in locoregional control with PORT (84%) compared with surgery alone (60%), which was concentrated in the pN1 subgroup (P = .036), but not the pN0 subgroup (P = .331)., Conclusion: PORT significantly improves locoregional control for intermediate risk OSCC., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of this study was to evaluate prognostic factors, locoregional control, and survival in locally advanced bucco-alveolar complex cancers., Methods: A retrospective review of 83 patients treated between January 2009 and December 2012 with bucco-alveolar complex cancers was conducted. All patients had surgery and adjuvant radiotherapy with intensity-modulated radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was performed using Kaplan-Meier and multivariable Cox regression model., Results: On univariate and multivariate analysis, perineural invasion (PNI) was found to be an independent adverse risk factor. Patients with PNI-positive disease had significantly worse 2-year disease-free survival (DFS), locoregional failure free survival, and overall survival (OS) as compared to patients with PNI-negative disease (P < 0. 001, 0.001 and < 0. 001) respectively., Conclusion: Compared with patients with PNI-negative disease, patients with PNI-positive disease had much worse outcome despite aggressive adjuvant treatment. It warrants escalation of therapy and modification in radiation portals to cover neural pathways in patients with PNI-positive disease., (© 2017 Wiley Periodicals, Inc.)

Background: The purpose of the present study was to investigate the role of tumor volume in the prognosis of patients with oral cavity squamous cell carcinoma (SCC)., Methods: One hundred twenty-three patients with T4a oral cavity SCCs underwent surgical treatment. The volumes of the primary cancer were calculated by the multiplication of 3 macroscopic dimensions of the surgical specimen and related to recurrence and death., Results: There were 54 recurrences (43.9%) and 75 deaths (60.9%). The mean tumor volume among the patients living without disease during the follow-up period was 28.2 cc, compared to 88.2 cc for patients living with disease, and to 78.9 cc for patients who died of the disease (p < .001). Multivariate analyses showed that volume and perineural invasion were independent factors for recurrence, whereas volume and lymph node metastasis were independent factors for death., Conclusion: Among patients who already have advanced cancers, tumor volume can significantly impact their prognoses. © 2017 Wiley Periodicals, Inc. Head Neck 39: 960-964, 2017., (© 2017 Wiley Periodicals, Inc.)