Objectives: . We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. Methods: . In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. Results: . No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. Conclusions . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. METHODS: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3–4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). CONCLUSIONS Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the clinical efficacy of sentinel node centered selective neck dissection in patients with early stage tongue cancer (T1T2N0). SUBJECTS AND METHOD: Lymphoscintigraphy was performed for 12 patients, subsequently followed by sentinel node centered selective neck dissection. The location of the sentinel node, pathological confirmation of node metastasis, and follow-up recurrence were analyzed. RESULTS: In total, 19 sentinel lymph nodes were identified. Of these, 18 were located in levels I to III, and one in level IV. After surgery, 3 patients (25%) were diagnosed with neck node metastasis: two experienced sentinel node metastasis and one experienced skipped metastasis. During follow-up, 3 of the 12 patients (25%) experienced recurrence. CONCLUSION: The recurrence of lymph node could be covered with supraomohyoid neck dissection, which indicates that it has superiority over sentinel node centered selective neck dissection in preventing recurrence in T1T2N0 tongue cancer patients.
Follow-Up Studies ; Humans ; Lymph Nodes* ; Lymphoscintigraphy ; Methods ; Neck Dissection* ; Neck* ; Neoplasm Metastasis ; Recurrence ; Tongue Neoplasms* ; Tongue* ; Treatment Outcome

PURPOSE: The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively. MATERIALS AND METHODS: Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively. CONCLUSION: INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.
Academies and Institutes ; Carcinoma, Squamous Cell* ; Disease-Free Survival ; Epithelial Cells* ; Follow-Up Studies ; Humans ; Methods ; Neck* ; Palatine Tonsil* ; Propensity Score* ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Tonsillar Neoplasms ; Tonsillectomy

PURPOSE: The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). MATERIALS AND METHODS: A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). RESULTS: In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. CONCLUSION: High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.
Adenoids* ; Carcinoma, Adenoid Cystic* ; Disease-Free Survival ; Fibroblast Growth Factor 2 ; Humans ; Immunohistochemistry ; Medical Records ; Multivariate Analysis ; Nasal Cavity ; Prognosis ; Proto-Oncogenes ; Receptors, Fibroblast Growth Factor ; Receptors, Platelet-Derived Growth Factor ; Risk Factors ; Vascular Endothelial Growth Factor A*

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.
Carcinoma, Squamous Cell* ; Cisplatin ; Disease Progression ; Drug Therapy ; Fluorouracil ; Head and Neck Neoplasms ; Head* ; Humans ; Induction Chemotherapy* ; Nasal Cavity* ; Neck* ; Orbit ; Orbit Evisceration ; Organ Preservation* ; Paranasal Sinuses

With the increase in life expectancy, age is no longer considered as a limitation for treatment. Nevertheless, the treatment of elderly patients with head and neck cancer (HNC) remains controversial. Here, we aimed to review our experience with the treatment for elderly patients, while particularly focusing on the differences among older old patients (septuagenarians vs. octogenarians). We retrospectively reviewed the records of 260 elderly patients who were assigned to 3 groups according to age: 70 years old ≤ group 1 < 75 years old, 75 years old ≤ group 2 < 80 years old, and group 3 ≥ 80 years old. The patients were assessed for comorbidities using the Adult Comorbidity Evaluation (ACE)-27, and the American Society of Anesthesia (ASA) physical status was also compared. Group 1, 2, and 3, consisted of 97, 102, and 61 patients, respectively. No significant difference in demographic data was noted among the groups. However, group 3 showed more comorbidities than groups 1 and 2. With regard to the initial treatment for HNC, radiation therapy (RT) was more frequently performed in group 3 than in groups 1 and 2. Among 7 patients of non-compliant to treatment in group 3, 6 patients had have performed RT. In group 3, a total of 18 patients underwent surgery, including microvascular free flap reconstruction and no significant difference in complications was observed postoperatively compared with group 1 and 2. Moreover, no significant difference was noted in overall survival between the groups, regardless of the treatment modality chosen. In conclusion, octogenarians with HNC should be more carefully managed than septuagenarians with HNC. Surgical treatment can be considered in octogenarians with HNC, if it can be tolerated.
Age Factors ; Aged ; Aged, 80 and over ; Comorbidity ; Head and Neck Neoplasms/mortality/*radiotherapy/*surgery ; Humans ; Retrospective Studies ; Survival Rate ; Treatment Outcome

With the increase in life expectancy, age is no longer considered as a limitation for treatment. Nevertheless, the treatment of elderly patients with head and neck cancer (HNC) remains controversial. Here, we aimed to review our experience with the treatment for elderly patients, while particularly focusing on the differences among older old patients (septuagenarians vs. octogenarians). We retrospectively reviewed the records of 260 elderly patients who were assigned to 3 groups according to age: 70 years old ≤ group 1 < 75 years old, 75 years old ≤ group 2 < 80 years old, and group 3 ≥ 80 years old. The patients were assessed for comorbidities using the Adult Comorbidity Evaluation (ACE)-27, and the American Society of Anesthesia (ASA) physical status was also compared. Group 1, 2, and 3, consisted of 97, 102, and 61 patients, respectively. No significant difference in demographic data was noted among the groups. However, group 3 showed more comorbidities than groups 1 and 2. With regard to the initial treatment for HNC, radiation therapy (RT) was more frequently performed in group 3 than in groups 1 and 2. Among 7 patients of non-compliant to treatment in group 3, 6 patients had have performed RT. In group 3, a total of 18 patients underwent surgery, including microvascular free flap reconstruction and no significant difference in complications was observed postoperatively compared with group 1 and 2. Moreover, no significant difference was noted in overall survival between the groups, regardless of the treatment modality chosen. In conclusion, octogenarians with HNC should be more carefully managed than septuagenarians with HNC. Surgical treatment can be considered in octogenarians with HNC, if it can be tolerated.
Age Factors ; Aged ; Aged, 80 and over ; Comorbidity ; Head and Neck Neoplasms/mortality/*radiotherapy/*surgery ; Humans ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUND AND OBJECTIVES: The adequate safety margin in tongue cancer is the most important prognostic factor for local recurrence and survival. This study aimed to evaluate the resection margins using a new technique of tongue resection under the guidance of guide wire under ultrasonography in patients with tongue cancer. SUBJECTS AND METHOD: In this prospective study, 10 patients with presurgical, biopsy-proven, clinical T1 or T2 tongue squamous cell carcinomas underwent resection under the guidance of guide wire inserted using ultrasonography. The data of resection margins of 37 patients who underwent partial glossectomy using the conventional method of palpation were used as control data. RESULTS: The mean safety margins (mm) of the experimental group were 7.59±4.30 (anterior), 8.56±4.69 (posterior), 5.25±3.01 (superior), 5.93±3.66 (inferior), 13.00±13.29 (medial), 5.78±2.64 (deep), and 6.67±3.06 (lateral). There were no differences in the safety margins between the two groups. CONCLUSION: Using guide wire under ultrasonography was not superior to the conventional method for partial glossectomy for having adequate resection margins.
Carcinoma, Squamous Cell ; Glossectomy ; Humans ; Methods ; Palpation ; Prospective Studies ; Recurrence ; Tongue Neoplasms* ; Tongue* ; Ultrasonography*

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca2+ ([Ca2+]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K+ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 microM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl- channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K+ current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca2+ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.
Carcinoma, Squamous Cell* ; Cell Death* ; Cell Line ; Cell Proliferation ; Head* ; Ion Channels ; Ionomycin ; Neck* ; Neoplasms, Squamous Cell