Influence of Social Vulnerability in Treatment and Prognosis of Squamous Cell Carcinoma of the Tongue.

OBJECTIVE: To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real-world contribution of specific disparities. STUDY DESIGN: Retrospective cohort study. SETTING: United States. METHODS: The Centers for Disease Control and Prevention-Social Vulnerability Index (SVI) and National Cancer Institute-Surveillance, Epidemiology, and End Results Program database were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow-up and survival across social vulnerability and 4 subcategories of social vulnerability. RESULTS: As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow-up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores. CONCLUSION: Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.

Advanced-stage tongue squamous cell carcinoma: a machine learning model for risk stratification and treatment planning.

BACKGROUND: A significant number of tongue squamous cell carcinoma (TSCC) patients are diagnosed at late stage. OBJECTIVES: We primarily aimed to develop a machine learning (ML) model based on ensemble ML paradigm to stratify advanced-stage TSCC patients into the likelihood of overall survival (OS) for evidence-based treatment. We compared the survival outcome of patients who received either surgical treatment only (Sx) or surgery combined with postoperative radiotherapy (Sx + RT) or postoperative chemoradiotherapy (Sx + CRT). MATERIAL AND METHODS: A total of 428 patients from Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Kaplan-Meier and Cox proportional hazards models examine OS. In addition, a ML model was developed for OS likelihood stratification. RESULTS: Age, marital status, N stage, Sx, and Sx + CRT were considered significant. Patients with Sx + RT showed better OS than Sx + CRT or Sx alone. A similar result was obtained for T3N0 subgroup. For T3N1 subgroup, Sx + CRT appeared more favorable for 5-year OS. In T3N2 and T3N3 subgroups, the numbers of patients were small to make insightful conclusions. The OS predictive ML model showed an accuracy of 86.3% for OS likelihood prediction. CONCLUSIONS AND SIGNIFICANCE: Patients stratified as having high likelihood of OS may be managed with Sx + RT. Further external validation studies are needed to confirm these results.

Population-based comparative survival analysis of surgery with or without adjuvant radiotherapy and non-operative primary radiotherapy in patients with early-stage oral tongue squamous cell carcinoma.

PURPOSE: Although recent clinical guidelines do allow primary radiotherapy for selected patients with early-stage oral tongue cancer, there has been little knowledge on the treatment outcomes of non-operative radiotherapy using modern treatment techniques. This study evaluated recent prognostic differences between primary radiotherapy and surgical resection in T1‒2N0 oral tongue squamous cell carcinoma. METHODS: Patients diagnosed with T1‒2N0 oral tongue squamous cell carcinoma were identified from the Surveillance, Epidemiology, and End Results database. After propensity score matching, the disease-specific survival of primary radiotherapy and surgery was compared. RESULTS: From a total of 8,458 patients initially identified, we defined matched cohorts: cohort A, comparing surgery alone vs. primary radiotherapy (n = 230 vs. 230), and cohort B, comparing surgery plus adjuvant radiotherapy vs. primary radiotherapy (n = 230 vs. 230). The 7-year disease-specific survival rates were 77% vs. 35% (cohort A) and 65% vs. 35% (cohort B) (P < 0.001 for all comparisons). Primary radiotherapy was independently associated with worse disease-specific survival in both cohorts A (hazard ratio 4.06; 95% confidence interval 2.53‒6.52) and B (hazard ratio 2.81; 95% confidence interval 1.96‒4.04). Time-course hazard rate function plots showed a distinct short-term risk increment in disease-specific mortality in the primary radiotherapy group. CONCLUSION: In the contemporary treatment era, the use of radiotherapy as a definitive treatment resulted in an inferior prognosis in patients with T1‒2N0 oral tongue squamous cell carcinoma. The present population-based data suggest that primary radiotherapy cannot be used as an alternative to surgical management and it needs to be avoided as much as possible in early-stage tumors.

Prognostic impact of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue: a retrospective study.

Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM.

MicroRNA-26b-5p suppresses the proliferation of tongue squamous cell carcinoma via targeting proline rich 11 (PRR11).

MicroRNAs (miRNAs) have been proved to be involved in many biological processes during tumorigenesis and progression, including cell proliferation and cell cycle progression. However, the potential role of miR-26b-5p in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, we demonstrated that miR-26b-5p was decreased in TSCC tissues in both TCGA-TSCC subset and eight paired samples from TSCC patients, while Proline Rich 11 (PRR11) was obviously increased. Transfection of miR-26b-5p mimics inhibited CALL7 cell proliferation by arresting the cells at the S/G2 transition. Meanwhile, miR-26b-5p inhibitor had the opposite biological functions. The results of luciferase activity and RNA-pulldown assays indicated that miR-26b-5p directly targeted the PRR11 3' -untranslated region in CAL27 cells. Furthermore, the effects of miR-26b-5p on cell cycle regulation were reversed after treatment with siRNA against PRR11. In summary, our findings indicate that miR-26b-5p induce cell cycle arrest in TSCC by targeting PRR11. Hence, targeting miR-26b-5p could be a promising therapeutic strategy for the treatment of TSCC.

The expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma.

P-cadherin (CDH3) is a cell-to-cell adhesion molecule that regulates several cellular homeostatic processes in normal tissues. Lack of CDH3 expression is associated with aggressive behavior in oral squamous cell carcinoma (OSCC). Previous studies have shown that CDH3 is downregulated in high-grade OSCC and its reduced expression is predictive for poorer survival. The aim of this study was to evaluate the expression and prognostic relevance of CDH3 in tongue squamous cell carcinoma (TSCC). A retrospective series of 211 TSCC and 50 lymph node samples were stained immunohistochemically with polyclonal antibody (anti-CDH3). CDH3 expression was assessed semi-quantitatively with light microscopy. Fisher's exact test was used to compare patient and tumor characteristics, and the correlations were tested by Spearman correlation. Survival curves were drawn by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate Cox regression was used to estimate the association between CDH3 expression and survival. CDH3 expression did not affect TSCC patient's disease-specific survival or overall survival. Strong CDH3 expression in the primary tumor predicted poor disease-specific and overall survival in patients with recurrent disease. CDH3 expression in lymph nodes without metastasis was negative in all cases. CDH3 expression was positive in all lymph node metastases with extranodal extension. In contrast to previous report about the prognostic value of CDH3 in OSCC, we were not able to validate the result in TSCC.

Impact on patients with oral squamous cell carcinoma in different anatomical subsites: a single-center study in Taiwan.

The incidence of oral cavity squamous cell carcinoma (OSCC) is particularly high in South Asia. According to the National Comprehensive Cancer Network, OSCC can arise in several subsites. We investigated survival rates and the clinical and pathological characteristics of OSCC in different anatomical subsites in the Taiwanese population. We retrospectively analyzed data for 3010 patients with OSCC treated at the Changhua Christian Hospital. Subsequently, we compared clinical and pathological features of OSCC in different subsites. Pathological T4 stage OSCCs occurred in the alveolar ridge and retromolar trigone in 56.4% and 43.7% of cases, respectively. More than 25% of patients with tongue OSCC and 23.4% of those with retromolar OSCC had lymph node metastasis. The prognosis was worst for hard palate OSCC (hazard ratio 1.848; p < 0.001) and alveolar ridge OSCC (hazard ratio 1.220; p = 0.017). Retromolar OSCC recurred most often and tongue OSCC second most often. The risk for cancer-related mortality was highest for hard palate OSCC, followed by alveolar ridge and retromolar OSCC. We found distinct differences in survival among the different subsites of OSCC. Our findings may also help prompt future investigations of OSCC in different subsites in Taiwanese patients.

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases. STUDY DESIGN: Retrospective study. METHODS: Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. RESULTS: Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease-free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate- or a high-grade budding score had a poor prognosis for RC according to the log-rank test. CONCLUSIONS: In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate- or high-grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. LEVEL OF EVIDENCE: Step 4 (Level 4) Laryngoscope, 131:2512-2518, 2021.

Elective node dissection versus observation for management of patients with early-stage cT1/T2N0 tongue carcinoma: A systematic review and meta-analysis of prospective studies.

OBJECTIVE: To carry out a meta-analysis of prospective literature comparing the clinical efficacy of elective neck dissection (END) vs observation (OBS) in patients with early-stage cT1/T2N0 tongue carcinoma. DESIGN/SETTING/PARTICIPANTS/OUTCOME MEASURES: We systematically reviewed four databases from inception to 30-October-2020. We considered all studies meeting the following PICOS conditions: (a) Patients: early-stage cT1/T2N0 tongue carcinoma, (b) Intervention: END, (c) Comparator: OBS, (d) Outcomes: local tongue recurrence, cervical nodal recurrence, disease-specific survival (DSS) rate, and disease-free survival (DFS) rate and (e) Study design: prospective reports. We pooled dichotomous data as relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Four studies (one case-control study and three randomised controlled trials) met our inclusion criteria. There were 448 eligible patients (225 and 223 patients were treated with END and OBS, respectively). END significantly correlated with improved DSS rate (RR = 1.15, 95% CI: 1.04-1.27, P = .007). Nonetheless, there were no significant differences between END and OBS groups regarding the rates of local tongue recurrence (RR = 1.23, 95% CI: 0.50-3.03, P = .65), cervical nodal recurrence (RR = 0.45, 95% CI: 0.16-1.27, P = .13) and DFS rate (RR = 1.08, 95% CI: 0.91-1.27, P = .38). Pooled analysis for cervical nodal recurrence was heterogeneous, and sensitivity analysis revealed a significantly lower cervical nodal recurrence rate in favour of END group (RR = 0.30, 95% CI: 0.13-0.67, P = .004). CONCLUSION: END correlated with a significant decrease in cervical nodal recurrence and improved DSS rate. END might be superior to OBS in patients with early-stage cT1/T2N0 tongue cancer.

Development and validation of multiparametric MRI-based nomogram for predicting occult metastasis risk in early tongue squamous cell carcinoma.

BACKGROUND: Nomograms are currently used in predicting individualized outcomes in clinical oncology of several cancers. However, nomograms for evaluating occult nodal metastasis of patients with squamous cell carcinoma of lateral tongue (SCCLT) have not been widely investigated for their functionality. This retrospective cohort study was designed to address this question. METHODS: This study was divided into primary and validation cohorts. The primary cohort comprised 120 patients diagnosed between 2012 and 2017, whereas the validation cohort included 41 patients diagnosed thereafter. The diagnostic value of multiparametric MRI, including radiologic tumor thickness threshold (rTTT) in three-dimensions, paralingual distance, and sublingual distance were investigated. A nomogram was developed based on stepwise logistic regression of potential predictors associated with nodal metastasis in the primary cohort and then tested for predictive accuracy in the validation cohort using area under the curve (AUC) and goodness-of-fit tests. RESULTS: Multivariate analysis, tumor size (odd ratio [OR] 15.175, 95% confidence interval [CI] 1.436-160.329, P = 0.024), rTTT (OR 11.528, 95% CI 2.483-53.530, P = 0.002), paralingual distance (OR 11.976, 95% CI 1.981-72.413, P = 0.005), and tumor location (OR 6.311, 95% CI 1.514-26.304, P = 0.011) were included in the nomogram to predict the likelihood of having cervical metastasis. A nomogram cutoff value of 210 points (sensitivity 93.8%, specificity 87.5%) was significantly different to classify the patients metastasis risk group (P < 0.001). Nomogram showed predictive accuracy with AUC 0.881 (95% CI 0.779-0.983, P < 0.001) and good calibration after the validation. CONCLUSIONS: A preoperative nomogram incorporating multiparametric MRI demonstrated good prediction and performed adequately in our study. Three-dimensional assessment of occult metastasis risk value obtained from this nomogram can assist in preoperative decision making for individual patients with early-stage SCCLT. The probability of nodal metastasis tended to be greater than 20% in patients with high metastasis risk or nomogram total score > 210 points.

Clinical Outcomes of Patients With pT1-T2N0 Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-year actuarial rates of local regional control, cancer-specific survival, and overall survival were calculated for the entire cohort and patients with/without adjuvant radiation. RESULTS: Ninety-six patients met the criteria with a median follow-up of 4 years; 14 had adjuvant radiation, while 82 had surgery alone. Two-year local regional control was 82.7% (75.4% to 90.8%) for the entire cohort, 84.9% (77.8% to 93.2%) for surgery only, and 70.7% (50.2% to 99.6%) for patients with adjuvant radiation. Two-year progression-free survival was 82.7% (75.3% to 90.8%). Of the 20 patients with recurrence, 11 (55%) were successfully salvaged. CONCLUSION: Local regional recurrence remains modest in early-stage OTSCC, but salvage is possible with high survival rates. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

A systematic review and meta-analysis of the prognostic role of age in oral tongue cancer.

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta-analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random-effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between-study heterogeneity (I2 ) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.

Effects of surgery on survival of patients aged 75 years or older with oral tongue squamous cell carcinomas.

The objective of this study is to assess prognostic value of surgery for elderly oral tongue squamous cell carcinomas (OTSCC) patients. Patients with OTSCC were extracted from the SEER database between 2010 and 2014. The distributions of categorical demographic and clinicopathological characteristics were determined for different age groups: the 75-79, 80-84, and 85-102 years old groups. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. A total of 1064 patients were analyzed. 75-79 years old patients tended to be male and rate of surgery declined with advancing age (P < 0.001). 75-79 years old patients more frequently presented with advanced stage compared to their older peers (P = 0.002). Compared to surgery groups, the hazard ratios for no surgery groups were 2.856 (95% CI 2.267-3.599; (P < 0.001)) for OS and 3.687 (95% CI 2.561-5.308; (P < 0.001)) for CSS in multivariable analysis. In subgroup analysis, the effect of no surgery was significantly associated with a higher risk of poor CSS in patients aged 75-79 years, 80-84 years and 85-102 years (P < 0.001, respectively). Our results showed that there were a series of factors contributing to poor outcomes in the elderly OTSCC patients, including clinicopathological characteristics and surgical management. Surgical resection is significantly associated with an improved OS and CSS, but further exploration in larger prospective clinical trials and better prognostic and predictive tools for select old patients for surgery are needed.

The prognostic role of histologic grade, worst pattern of invasion, and tumor budding in early oral tongue squamous cell carcinoma: a comparative study.

Major pathology guidelines often mandate stating the histologic grade as a component of the pathology report for various types of cancer. However, the prognostic value of histologic grade in head and neck squamous cell carcinoma (HNSCC) is controversial at best, and there is a need for more reliable prognostic histologic factors to better stratify and manage patients with HNSCC. In this study, we compared three relevant histopathologic features (histologic grade, worst pattern of invasion (WPOI), and tumor budding) in a large single-center retrospective cohort of early oral tongue squamous cell carcinoma (OTSCC) with tumor greatest dimension ≤ 4 cm. Only histologic grade predicted distant metastasis free survival (DMFS) on univariate analysis. Tumor budding was associated with nodal metastasis, overall survival (OS), regional recurrence-free survival (RRFS), and DMFS and was a significant predictor for nodal metastasis on the multivariable logistic regression model. WPOI 5 was associated with high frequency of nodal metastasis and shortened OS and was an independent adverse prognostic factor for OS on multivariate analysis using the Cox proportional hazards model. WPOI and tumor budding were prognostically more relevant than histologic grade. Consideration should be given to include WPOI and tumor budding in the pathology reporting of OTSCC.

Circ_0000003 regulates glutamine metabolism and tumor progression of tongue squamous cell carcinoma via the miR­330­3p/GLS axis.

Various circular RNAs (circRNAs) have been shown to exert vital functions in tongue squamous cell carcinoma (TSCC). However, their roles in TSCC progression remain to be elucidated. This research aimed to investigate the role and mechanism of hsa_circ_0000003 (circ_0000003) in TSCC progression. Here, we found that circ_0000003 expression was upregulated in TSCC tissues and cell lines, and high circ_0000003 expression was correlated with advanced TNM stage, increased tumor size and poor patient survival. Circ_0000003 was revealed to facilitate cell proliferation, migration and invasion of TSCC cells. Mechanistically, we found that circ_0000003 acted as a competing endogenous RNA (ceRNA) that sponged miR­330­3p, thereby elevating glutaminase (GLS) expression. Accordingly, cell invasion, migration, glutamine consumption, α­ketoglutarate (α­KG) production and ATP production were significantly decreased by circ_0000003 knockdown in TSCC cells, and these effects were reversed by miR­330­3p inhibition. In conclusion, circ_0000003 facilitates TSCC cell proliferation, migration, invasion and glutamine catabolism by regulating the miR­330­3p/GLS pathway.

The role of electrochemotherapy with intratumoral bleomycin for early tongue carcinoma.

BACKGROUND: The role of electrochemotherapy (ECT) using intratumoral bleomycin and electroporation as a first line treatment for oral tongue carcinoma has not been defined. AIMS/OBJECTIVES: To evaluate the method of ECT in oral tongue carcinoma. MATERIAL AND METHODS: Twenty-one successive patients with primary T1-T2 oral cancer predominantly of the oral tongue underwent either ECT (test; n = 9), or standard surgical resection and reconstruction (control; n = 12). Outcome variables were: local recurrence rates, 10-year-survival, adverse events, treatment cost, and quality of life. RESULTS: The 10-year local recurrence rate (44.4%) was higher and the tumour-specific survival rate (55.6%) was lower in the ECT group compared to the control group (17% and 91.6%, respectively). Postoperative haemorrhage, dysphagia, and pain were more frequent in ECT patients, treatment time was shorter, but treatment cost was higher. Quality of life was not improved by ECT. CONCLUSIONS AND SIGNIFICANCE: Our results indicate that ECT seems not as suitable for the treatment of early tongue cancer as it is for neoplastic and metastatic skin lesions and less favourable than standard surgical therapy.

Clinicopathological and Prognostic Analysis of PD-L1 and PD-L2 Expression in Surgically Resected Primary Tongue Squamous Cell Carcinoma.

BACKGROUND/AIM: The expression of tumor-associated programmed death-ligand 1 (PD-L1) predicts clinical responses to PD-1-directed immunotherapy. The expression levels of PD-L2, another PD-1 ligand, and its relationship with responses to PD-1-targeting therapy in oral squamous cell carcinoma (OSCC) remain unclear. Furthermore, the clinicopathological characteristics and prognostic effects of the expression of PD-L1 and PD-L2 in OSCC have not yet been elucidated. MATERIALS AND METHODS: The expression of PD-L1 and PD-L2 was immunohistochemically examined in 98 tongue carcinomas. Furthermore, the expression levels of PD-L1 and PD-L2 in OSCC cell lines and their relationships with those of MMP2 and MMP9 were assessed. RESULTS: The expression levels of PD-L1 and PD-L2 correlated with those of MMP2 and MMP9. The expression of PD-L1 and/or PD-L2 was detected in OSCC cells, and their levels correlated with those of MMP9. The prognosis of patients with PD-L1- and PD-L2-positive tumors was significantly worse. CONCLUSION: PD-L1 and PD-L2 status is potentially a novel predictor of the prognosis of OSCC and provides a rationale for the development of novel immunotherapies.

Prognostic Indicators in Base of Tongue Adenocarcinoma: A Population-Based Analysis.

INTRODUCTION: The objectives of this investigation are to characterize the epidemiology of base of tongue adenocarcinoma utilizing a population-based database and to identify prognostic factors that may affect survival. METHODS: A retrospective cohort study was conducted using the Surveillance, Epidemiology, and End Results database. Univariate Kaplan-Meier analysis and multivariate Cox-regression analysis were performed to evaluate the association of suspected prognostic factors with survival. Overall survival (OS) and disease-specific survival (DSS) were the primary outcome measures. RESULTS: A total of 176 cases were eligible based on inclusion criteria. The 5-year OS and DSS were 49% and 66%, respectively. On multivariate analysis, surgical management was associated with improved OS and DSS (OS hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.20-0.58, P < .001; DSS HR: 0.20, 95% CI: 0.09-0.48, P < .001), while higher tumor grade was associated with worse OS and DSS (OS HR: 1.58, 95% CI: 1.14-2.19, P = .006; DSS HR: 1.68, 95% CI: 1.01-2.79, P = .045). Administration of chemotherapy or radiation did not have a significant association with OS or DSS. CONCLUSION: This investigation is the largest to date to analyze the base of tongue adenocarcinoma as its own entity. Surgery remains the mainstay of treatment, and lower tumor grade is associated with improved survival in these patients. Administration of radiation or chemotherapy was not associated with improved survival.

Prognostic Relevance of Macrophage Phenotypes in High-grade Oral Tongue Squamous Cell Carcinomas.

Tumor-associated macrophages (TAMs) are part of the tumor microenvironment, broadly divided into M1 and M2 phenotypes. M1 macrophages, commonly identified by staining the CD11c antigen, have an antitumour immunity role, while M2 macrophages, expressing the CD163 antigen, are involved in tumor progression. Little is known about M1 and M2 phenotypes in the context of the oral tongue squamous cell carcinomas (OTSCC), a subgroup of oral cancer with peculiar clinical behavior. This study evaluated the macrophage polarization in OTSCC specimens to examine their prognostic relevance. To this end, specimens from 71 OTSCC patients graded as G1 or G3 were investigated for CD11c and CD163 expression. Immunohistochemical staining of TAMs was evaluated in tumor nests, tumor inflammation area (TIA), and tumor stroma. To analyze the expression of CD11c and CD163, the percentage of positive cells was scored as 0 (negative), 1 (<10%), 2 (11% to 50%), 3 (51% to 80%), and 4 (>80%). The staining intensity was scored as 0 (negative), 1 (weak), 2 (moderate), and 3 (intense). Higher expression of both CD163+ and CD11c+ macrophages in inflammation area positively correlated with G3 grade, both in extension and intensity. Focusing on G3 tumors, survival curves showed better disease-free survival in patients with high CD11c expression in the TIA. Presence of CD163 expression in TIA was associated with worse disease-free survival. This study evaluated, for the first time, the distribution of M1 and M2 macrophages in relation to the pathologic grade in OTSCC, highlighting the prognostic relevance of analyzing the localization of TAMs.

Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)-related HNSCC to those of older patients. METHODS: A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114). RESULTS: When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, P < .01) and females (40.7% vs 24.6% of older patients, P = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, P = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, P = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients (P = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, P < .01). CONCLUSIONS: Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.