The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma.

BACKGROUND: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. RESULTS: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024). CONCLUSION: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Impact of dysplasia at resection margin on oncologic outcome after curative resection of oral tongue squamous cell carcinoma: significance of high-grade dysplastic resection margin.

BACKGROUND: This study aimed to compare the oncologic outcomes among negative, close, positive, and dysplasia resection margins (RMs) with oral tongue squamous cell carcinoma (OSCC) and to investigate the impact of dysplastic RMs. METHODS: The 565 patients were retrospectively analyzed and divided into four groups according to RM. Dysplasia was classified into mild, moderate, and severe subgroups. RESULTS: RMs consisted of negative (62.1%), close (27.1%), positive (2.1%), and dysplastic (8.7%). In multivariate analysis, advanced T/N stages and positive RM were significant risk factors for overall survival, while dysplasia at the RM was not a significant risk factor for locoregional recurrence or overall survival. In subgroup analysis of patients with dysplastic margin, RM with severe dysplasia showed higher recurrence than mild and moderate dysplasia. CONCLUSIONS: Dysplastic RM was not a risk factor for recurrence and survival. Severe dysplasia RM should be carefully observed due to higher recurrence compared to other dysplasia RMs.

Comparative analysis of volumetric changes between resection volume of oral tongue cancer and post operative volume of radial forearm flaps.

OBJECTIVES: This study investigates the relationship between the total volume of oral tongue cancer pre-operatively and the RFFF volume post-operatively. MATERIALS AND METHODS: A total of 52 DICOM imaging datasets (CT or MRI) of 26 patients were included in this study. The volume of the desired structure was quantified using semi-automatic segmentation using the software ITK-SNAP. All extracted measurements were validated by two further clinicians at separate instances. RESULTS: The variation of MeanVolTu can be predicted by MeanVolFlap moderately reliable with 59.1% confidence (R-Qua: 0.591). ANOVA Testing to represent how well the regression line fits the data, resulted in the overall regression model being statistically significant in predicting the MeanVolTu (p < 0.001). The flap volume may be predicted using the following algorithm: MeanVolFlap0 = 3241,633 + 1, 322 * MeanVolTu. CONCLUSION: The results of this study show positive correlation between tumor volume and flap volume, highlighting the significance of efficient flap planning with increasing tumor volume. A larger extraction volume of the radial forearm free flap from the donor site compromises the forearm more, thus increasing the probability of post-operative complications. CLINICAL RELEVANCE: Radial forearm free flap design in accordance with its corresponding 3D tumor volume.

Diverging incidence trends of oral tongue cancer compared to other head and neck cancers in young adults in France.

While head and neck cancer incidence decreased worldwide due to reduced tobacco and alcohol consumption, oral tongue cancer (OTC) incidence has been reported to be increasing in several countries. Our study examines the incidence trends of OTC in France from 1990 to 2018, globally and by age; and compares the incidence trends with the evolution of the incidence of other human papilloma virus-unrelated head and neck squamous cell carcinoma, that is, cancers of the remaining subsites of the oral cavity (RSOCC) and laryngeal cancers for the period 1990 to 2018. World age-standardized incidence rates of oral tongue cancers (C02), cancers of the remaining subsites of the oral cavity (RSOCC, C03-06) and laryngeal cancers (C32) were estimated using the French National Network of Cancer Registries for the period 1990 to 2018. Trends in national incidence rates were estimated from a mixed-effect Poisson model including age and year effects using penalized splines and a district-random effect. In women aged 30 and 40, a significant increase in OTC incidence was observed, while ROSCC showed a nonsignificant incidence decrease. In young men aged 25, a marginally significant increase of OTC incidence years was observed, while incidence rates of RSOCC significantly declined. The results suggest a tendency towards diverging incidence trends for OTC compared to RSOCC and laryngeal cancer in young adults. The observed trends may reflect changes in underlying exposures or emerging exposures not yet identified, and stress the need to further investigate the etiology of oral tongue cancers.

Tertiary lymphoid structures associate with improved survival in early oral tongue cancer.

BACKGROUND: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). METHODS: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. RESULTS: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014). CONCLUSION: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer.

BACKGROUND: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. METHODS: Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. RESULTS: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . CONCLUSION: The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

The mutational landscape of early- and typical-onset oral tongue squamous cell carcinoma.

BACKGROUND: The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing among younger birth cohorts. The etiology of early-onset OTSCC (diagnosed before the age of 50 years) and cancer driver genes remain largely unknown. METHODS: The Sequencing Consortium of Oral Tongue Cancer was established through the pooling of somatic mutation data of oral tongue cancer specimens (n = 227 [107 early-onset cases]) from 7 studies and The Cancer Genome Atlas. Somatic mutations at microsatellite loci and Catalog of Somatic Mutations in Cancer mutation signatures were identified. Cancer driver genes were identified with the MutSigCV and WITER algorithms. Mutation comparisons between early- and typical-onset OTSCC were evaluated via linear regression with adjustments for patient-related factors. RESULTS: Two novel driver genes (ATXN1 and CDC42EP1) and 5 previously reported driver genes (TP53, CDKN2A, CASP8, NOTCH1, and FAT1) were identified. Six recurrent mutations were identified, with 4 occurring in TP53. Early-onset OTSCC had significantly fewer nonsilent mutations even after adjustments for tobacco use. No associations of microsatellite locus mutations and mutation signatures with the age of OTSCC onset were observed. CONCLUSIONS: This international, multicenter consortium is the largest study to characterize the somatic mutational landscape of OTSCC and the first to suggest differences by age of onset. This study validates multiple previously identified OTSCC driver genes and proposes 2 novel cancer driver genes. In analyses by age, early-onset OTSCC had a significantly smaller somatic mutational burden that was not explained by differences in tobacco use. LAY SUMMARY: This study identifies 7 specific areas in the human genetic code that could be responsible for promoting the development of tongue cancer. Tongue cancer in young patients (under the age of 50 years) has fewer overall changes to the genetic code in comparison with tongue cancer in older patients, but the authors do not think that this is due to differences in smoking rates between the 2 groups. The cause of increasing cases of tongue cancer in young patients remains unclear.

Histopathologic grading and its relationship with outcome in oral tongue squamous cell carcinoma.

BACKGROUND: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. OBJECTIVES: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). METHODS: Clinical and follow-up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. RESULTS: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07-5.27; P = 0.026] and patients with BD model high-grade tumors (HR: 2.99; 95% CI: 1.03-8.68; P = 0.034) were significantly associated with a poor 5-year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00-4.99; P = 0.050). None of the grading systems studied was associated with 5-year disease-free survival rates. CONCLUSIONS: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC.

Histopathologic prognostic indices in tongue squamous cell carcinoma.

PURPOSE: Consistent prognosticators are needed to guide adjuvant treatment in tongue squamous cell carcinoma (SCC). We validate the prognostic significance of histopathologic parameters in surgically treated tongue SCC. METHODS: Archival specimens of 88 consecutive patients who were treated surgically for tongue SCC from 2003 to 2016 were re-analyzed by one pathologist. Patient records were retrospectively reviewed. Prognosticators of recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were identified using multivariate analysis. RESULTS: Tumor depth of invasion (DOI) > 6 mm (OR 4.76; 95%CI 1.22-18.5; p = 0.024) and lymphovascular invasion (OR 5.61; 95%CI 1.00-31.5; p = 0.05) were independent predictors of nodal metastases. The overall 5-year RFS, OS and DSS were 70%, 82% and 84% respectively. Positive margins predicted poor RFS (HR 3.91; 95%CI 1.58-9.65; p = 0.003) and local recurrence-free survival (HR 4.96; 95%CI 1.36-18; p = 0.015). Presence of nodal metastases (HR 5.03; 95%CI 1.73-14.6; p = 0.003), tumor DOI > 6 mm (HR 9.91; 95%CI 1.26-78.0; p = 0.029) and positive margins (HR 8.26; 95%CI 2.75-24.8; p < 0.001) were independent predictors of poor OS. Presence of nodal metastases (HR 3.87; 95%CI 1.17-12.8; p = 0.027) and positive margins (HR 12.3; 95%CI 3.54-42.9; p < 0.001) also independently predicted poor DSS. CONCLUSION: Margins' status was the only independent predictor of local recurrence. Tumor DOI, nodal and margin status were key prognosticators of survival and may determine the necessity for adjuvant therapy.

Prognostic outcomes of treatment naïve oral tongue squamous cell carcinoma (OTSCC): a comprehensive analysis of 14 years.

OBJECTIVES: To analyze the factors predicting survival outcomes in treatment naïve oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: A comprehensive review of 531 oral tongue carcinoma patients treated with upfront surgery followed by adjuvant radiotherapy or chemoradiotherapy was conducted from 2004-2018. RESULTS: The mean age of presentation was 53 years (11-86) with a male to female ratio of 1.3:1. The associated risk factors were smoking (21%), betel nut (16%), naswar (9%) and alcohol (1%). Most of the cases were either well (45.1%) or moderately (46.2%) differentiated. Surgery was performed in 164 patients alone while 368 were treated with surgery in combination with adjuvant modalities. Overall (OS) and disease free survival (DFS) were 66 and 71%, respectively, with a median follow up of 2.5 years. Cox regression analysis showed nodal positivity, increased depth of invasion (DOI) and higher lymph node ratio (LNR) as significant prognosticators impacting OS and DSS. CONCLUSION: Nodal volume, DOI and LNR are the most consistent predictors of poor outcome in OTSCC. Nodal positivity, depth of invasion > 5 mm and lymph node ratio > 0.04 adversely affect OS and DSS.

Histological characteristics of early-stage oral tongue cancer in young versus older patients: A multicenter matched-pair analysis.

Little is known about the histopathological characteristics that may differentiate early oral tongue cancer (OTSCC) between young and older patients. From a total of 311 cases diagnosed with clinically early-stage OTSCC at 6 institutions, only 42 patients were young patients were aged ≤45 years. For comparison, 42 patients >60 years old were matched for center of management, clinical stage and gender. We compared epithelial and stromal histopathologic parameters between the two groups. Most of the parameters were similar between the two groups, although the young patients appeared to have marginally higher intensity of tumor budding, histologic risk score, infiltrative pattern of invasion and tumor-stroma ratio. However, none of the factors showed significant difference when comparing the two groups. The histological parameters reflect mechanisms of invasive growth and tissue response to invasive growth, but not the etiological difference in OTSCC between young and older patients. Further investigations are necessary to compare the genetic background of early OTSCC in the two groups.

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro.

Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and - 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and - 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR.

Risk of oral tongue cancer among immunocompromised transplant recipients and human immunodeficiency virus-infected individuals in the United States.

BACKGROUND: Oral tongue cancer incidence has increased among whites in the United States; however, the cause remains unknown. If an infectious agent is implicated, then elevated risk would be expected among immunosuppressed individuals. METHODS: By using population-based registry linkage information from the US Transplant Cancer Match and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Cancer Match studies, the authors examined the risk of oral tongue squamous cell carcinoma (SCC) among immunocompromised transplantation recipients and HIV-infected individuals. In addition, the risks of oropharyngeal SCC (strongly related to human papillomavirus infection; modestly affected by immunosuppression), other tobacco/alcohol-related oral cavity SCCs (not thought to be infection/immunosuppression-related), and non-Hodgkin lymphoma of oral cavity/pharynx (strongly related to Epstein-Barr virus; profoundly affected by immunosuppression) were evaluated. RESULTS: Compared with the general population, the risk of non-Hodgkin lymphoma was strongly increased (standardized incidence ratio [SIR] > 8.0). The risk of all SCCs was modestly and similarly elevated among transplantation recipients (SIR range, 2.2-2.7; Pheterogeneity = .2); whereas, among HIV-infected individuals, the risk of oral tongue SCC was higher compared with the risk of other SCCs (SIR, 3.0 vs 1.7 [for oropharyngeal SCCs] and 2.3 [for other oral cavity SCCs]; Pheterogeneity < .001). The risk of SCCs was significantly higher among men, older individuals, and whites; and risk increased with the time since transplantation/AIDS onset. The risk of oral tongue SCC was significantly higher among HIV-infected men who have sex with men compared with the average risk in HIV-infected individuals (adjusted incidence rate ratio = 2.0). CONCLUSIONS: Similar modest increases in the risk of oral tongue and other oral cavity SCCs do not suggest that an infectious agent or exposure profoundly affected by immunosuppression underlies the increase in oral tongue cancer. Cancer 2018;124:2515-22. © 2018 American Cancer Society.

Prognostic impact of tumour-stroma ratio in early-stage oral tongue cancers.

AIMS: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi-institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)-stained tumour-resection slides in a series of early-stage (cT1-2N0) OTSCC patients. METHODS AND RESULTS: A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early-stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma-rich group. In a multivariate analysis, the stroma-rich group had worse disease-free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17-2.79, P = 0.008], and higher cancer-related mortality (HR 1.71, 95% CI 1.02-2.86, P = 0.03). The combination of the highest-risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71-6.82, P = 0.004) and cancer-related mortality (HR 11.63, 95% CI 3.83-35.31, P < 0.001). CONCLUSIONS: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early-stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE-stained slides.

Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis.

Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n = 15; Stage II, n = 30; Stage III, n = 7; Stage IV, n = 13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress.

The effect of preoperative neutrophil, platelet and lymphocyte counts on local recurrence and survival in early-stage tongue cancer.

The aim of this study was to investigate the predictive value of preoperative neutrophil, platelet and lymphocyte counts in local recurrence and survival in the patients operated for early-stage squamous cell carcinoma (SCC) of the tongue. 57 patients who underwent surgery for early-stage (stage 1-2) SCC of the tongue were enrolled in the study. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and neutrophil × PLR value (N × PLR) were used as outcome measures. Local recurrence was detected in 11 (19.3 %) patients during follow-up period. Mortality was seen in 7 (12.3 %) patients. 37 (64.9 %) patients had stage 1 and 20 (35.1 %) patients had stage 2 tumor. NLR, PLR and N × PLR cutoff values were determined as 2.26, 146,855 and 689,912, respectively, by receiver operating characteristic analysis. The relationship between NLR, PLR, N × PLR and local recurrence was statistically significant according to these cutoff values (p values 0.021, 0.020, 0.017, respectively). We suggest that NLR, PLR and N × PLR may be used to predict local recurrence, while their use in overall and disease-free survival is limited. Further studies involving large patient groups are required.

P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue.

BACKGROUND: Squamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol. METHODS: We determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival. RESULTS: Our results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival. CONCLUSION: Our study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.

Subtotal glossectomy with conservation of the hyo-styloglossus unit (HSU): a new pivotal concept for preserving tongue function in extended glossectomy.

Objective: The local spread of oral tongue squamous cell carcinoma (OTSCC) follows pathways of dissemination along areas of lesser resistance. In more advanced scenarios, the tumor can extend beyond the hemi-tongue of origin, by passing through the lingual septum and following the fibers of the transverse muscle. This can lead to the invasion of the contralateral extrinsic muscles, the first being the genioglossus and more laterally the hyoglossus. An anatomically guided surgical resection of the tumor can be planned to ensure both oncological safety and an acceptable functional outcome. This approach aims to preserve the hyo-styloglossus unit (HSU) whenever feasible. Methods: Between January 2019 and November 2022, six patients received extended glossectomy Type B (EG Type B), with preservation of the HSU. Preliminary oncological results and functional results in terms of swallowing (FOIS score) and quality of life (MDADI) are presented. Results: Five out of the six patients are alive and disease-free, while one patient died due to other causes. All patients who were candidates for an EG Type B underwent a swallowing assessment prior to surgery and followed daily postoperative swallowing training. At discharge, the patients continued swallowing training in an outpatient clinic. Five out of the six patients reached a full oral diet within 1 year of follow-up. Conclusion: The oncological results confirm the safety of this technique. The importance of preserving the HSU, the minimal functional unit, shows very encouraging results in terms of swallowing rehabilitation.

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis.

BACKGROUND: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. PATIENTS AND METHODS: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. RESULTS: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759-0.878] in OTC, 0.687 [0.559-0.815] in HPV-positive OPC, 0.823 [0.642-1.000] in HPV-negative OPC, and 0.907 [0.841-0.973] in HPC. CONCLUSION: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

Sentinel Lymph Node Biopsy (SLNB) for Early-Stage Head and Neck Squamous-Cell Carcinoma of the Tongue: Twenty Years of Experience at I.N.T. "G.Pascale".

Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1-2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB's efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB's reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection.