Tongue Tumors Research Articles

Abstract 6049: Exogenous serine promotes cancer stem cells in oral squamous cell carcinoma

Abstract Cancer development and progression is associated with metabolic reprogramming of tumor cells required to meet their proliferative, bioenergetic and survival challenges. Some metabolites, including a non-essential amino acid, serine, have been shown to play a role in tumorigenesis by promoting aggressive cell states, such as cancer stem cells (CSCs). Previous studies from our laboratory showed that the nuclear branch of the Wnt/β-catenin signaling pathway, the β-catenin/CBP/MLL1 axis, enhanced CSC states during oral squamous cell carcinoma (OSCC) evolution through H3K4 trimethylation (H3K4me3) and epigenetic remodeling of the chromatin landscape. Given that metabolism has also been shown to modulate cell plasticity via epigenomic modifications, we have aimed to decode the relationship between serine synthesis and cell identity in OSCC. We have shown that under serine starvation conditions, OSCC cells upregulate steady-state mRNA and protein levels of serine synthesis pathway enzymes. The latter is associated with an increase in the by-product, alpha-ketoglutarate (αKG), a co-substrate for nuclear αKG-dependent dioxygenases, which demethylate histone marker H3K27me3 and de-repress differentiation-associated genes. Furthermore, increased production of αKG is associated with downregulation of the β-catenin/CBP/MLl1 complex and CSC-associated H3K4me3. In this study, we used human OSCC cell lines CAL27 and HSC3, derived from a primary tongue tumor and a metastatic site, respectively. Each cell line was cultured in either complete medium or serine starvation medium. Serine starvation conditions led to a downregulation of H3K27me3 along with H3K4me3, promoting a switch from cancer stem cell to differentiation-enhancing chromatin landscape. The observed changes in cell plasticity were further investigated through tumorsphere formation, a surrogate assay for cancer stem cells. We found that OSCC CAL27 and HSC3 cells readily formed tumorspheres replete with stem cell markers BMI1, KRT14 and SOX2, under non-adhesive conditions when grown in complete media, supporting our findings that utilization of exogenous serine enables OSCC cells to maintain stemness. Our findings suggest that a switch from exogenous serine uptake to the endogenous serine biosynthesis promotes OSCC cell differentiation concomitant with the loss of CSC identity. Citation Format: Stacy Ann Jankowski, Nina C. Hardy, Maria A. Kukuruzinska. Exogenous serine promotes cancer stem cells in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6049.

Abstract 4238: Specific oral microbiome is closely associated with oral potentially malignant disorders and oral squamous cell carcinoma

Abstract Background: Bacterial and virus infection may cause pre-malignant and malignant disorder such as hepatocellular carcinoma and cervical cancer. Recent studies reported that oral bacterium is associated with gastric and colon cancer. However, it is not clear yet if the oral microbiome affects the development of pre-malignant disorder in oral cavity and oral cancer. Thus, this study aims to identify the periodontal pathogen candidates involved in the onset and progression of oral squamous cell carcinoma (OSCC). Materials and Methods: Saliva was collected from 112 patients without oral mucosal diseases (OMDs) as control, 36 patients with oral potentially malignant disorders (OPMDs), and 104 patients with OSCC, and DNA was extracted in each sample. Periodontal examinations were performed on all patients. Endpoint-PCR was performed on seven species of oral pathogens using the extracted DNA. 16S ribosomal RNA (rRNA) was utilized for analysis of oral microbiome with 20 samples in each group. 4-nitroqquinoline-1-oxide (4-NQO)-induced tongue tumor model in mice was analyzed with or without endotoxin of one of the oral bacteria, Porphyromonas gingivalis (P. gingivalis). Results: From the statistical analysis of the clinical parameters, periodontal disease tended to worsen in the OMPD and OSCC groups compared to the control group. The number of oral bacteria was significantly higher in the OSCC group than those in other groups. From PCR results, the detection rates of P. gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola were significantly higher in the OSCC group than those in the control group. From 16S rRNA analysis, the relative abundance of Prevotella buccae and intermedia was significantly higher in OSCC groups than in the control group. Furthermore, the relative abundance of P. gingivalis was higher in the OSCC group compared to other groups, regardless of age and the number of teeth. In mouse model, mice treated with P. gingivalis-derived endotoxin developed oral leukoplakia at earlier time points and tumors significantly higher lesions compared to control group. Conclusion: These results suggest that specific periodontal pathogens are present in the oral cavity of OPMDs and OSCC patients and those changes in the bacterial flora due to their presence may contribute to the onset and progression of OMDs. Citation Format: Mitomu Kioi, Hiroshi Isono, Shintaro Nakajima. Specific oral microbiome is closely associated with oral potentially malignant disorders and oral squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4238.

Abstract 4743: Wnt/beta-catenin mediated epigenetic modifications drive age-dependent oral squamous cell carcinoma evolution

Abstract Oral Squamous Cell Carcinoma (OSCC) is a devastating disease associated with high morbidity, poor survival, and few therapeutic options. This malignancy is driven, in part, by epigenetic reprogramming of the chromatin landscape directed by β-catenin in complex with CREB-binding protein (CBP) and mixed lineage leukemia methyltransferase 1 (MLL1). The β-catenin/CBP/MLL1 complex promotes an open chromatin structure by enabling transcription of genes associated with cell plasticity, including cancer stem cells and cells with partial EMT (p-EMT) phenotypes. Growing evidence indicates that cell plasticity and cellular senescence are integral processes shared by cancer and aging. Given that the median age of OSCC diagnosis is 66 years, it is likely that aging promotes OSCC evolution to advanced disease. To examine the effects of aging on OSCC evolution, we adapted a syngeneic mouse model of tobacco-associated oral carcinogenesis. This model utilizes a mouse cell line, 4MOSC1, derived from 4-nitroquinoline-1 oxide- (4NQO)-induced tongue tumor which, when implanted into mouse tongues, generates tumors that recapitulate human OSCC mutanome. The growth of 4MOSC1 derived orthotopic tumors was studied in 6- and 80-week-old mice. Tumors were allowed to develop for 18 days, after which they were harvested and processed for single cell RNA sequencing, histopathology and immunofluorescence (IF) analyses. Results showed that tumors grew at a faster rate and to a greater overall size in old mice compared to their young cohorts. OSCC harvested from the old mice displayed statistically significant reduction in membranous E-cadherin concomitant with increased Cbp and H3K4me3 abundance, suggesting an age-associated upregulation of β-catenin/Cbp/Mll1 epigenetic activity. Increased expression of Bmi1, keratin 14, and podoplanin supported increased cell plasticity in OSCC from aged mice. Further, these tumors exhibited augmented cellular senescence, as judged by the disruption of lamin B1-associated nuclear membrane integrity, and by an increased cell population with markers of senescence from single cell sequencing analyses. These data suggest that aging is associated with increased β-catenin/Cbp/Mll1 epigenetic signaling, cell plasticity and cellular senescence, which collectively contribute to the evolution of OSCC. Citation Format: Emily R. Fisher, Anthony Spinella, Nina C. Hardy, Xaralabos Varelas, Manish Bais, Maria A. Kukuruzinska. Wnt/beta-catenin mediated epigenetic modifications drive age-dependent oral squamous cell carcinoma evolution. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4743.

The chemotherapeutic activity of areca nut extract increased stromal tumor-infiltrating lymphocytes in 4-nutriquinoline-1-oxide-tumor-induced Sprague-Dawley rats

Background: Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers with a high mortality rate. The biodiversity source in Indonesia makes areca nut a potential antioxidant in treating disease. Objective: The study aimed to evaluate the chemotherapeutic effect of areca nut extract in 4-nutriquinoline-1-oxide (NQO)-tumor-induced rats. Methods: Twenty-eight male Sprague-Dawley rats were divided into four groups. Group 1 served as the control group, group 2 was 4NQO-induced rats without treatment, and groups 3 and 4 were given 4NQO-tumor inducer with 500 and 1000 mg/kg BW of areca nut extract, respectively. The rats in groups 2,3, and 4 received 30 ppm of 4NQO tumor inducer in drinking water for 12 weeks. In the end, all rats were euthanized and the tongue was removed. The body, liver, kidney, heart, and lungs weights were measured. Tongue tumor volume and dysplasia lesions were analyzed. The tumor-infiltrating lymphocytes (TILs) in the tumor and stromal area were scored semi-quantitatively associating the infiltrate grade (0-3) and analyzed histologically. Results: There were significant differences in body weight loss between the initial and final phases in groups 1 and 2 (p<0.05). The areca nut at doses of 500 and 1000 mg/kg BW significantly reduced the tumor size compared with groups 1 and 2 (p<0.05). The incidence of OSCC in rats with 500 and 1000 mg/kg BW of areca nut extract after 22 weeks was 0%, but the dysplasia lesions were observed at 28.57% and 85.71%, respectively. The highest mean of stromal TILs was in group 3 and there were significant differences in stromal TILs between groups 2 and 3 (p<0.05). Conclusion: Areca nut extract exerts a chemotherapeutic activity in 4NQO-induced rats by inducing infiltrating lymphocytes in the stromal tumor area on the OSCC lesion of the tongue.

Twelve Years of Establishing the Strategies for Tongue Reconstruction.

Reconstruction after resection of malignant tongue tumors remains one of the most difficult problems in head and neck oncology. Recent trends in tongue reconstruction have focused on optimizing speech and swallowing functions and maximizing quality of life. In the recent literature, several reconstructive strategies including regional flaps and free flaps have been described. A case series of 328 patients underwent oral tongue reconstruction between March 2011 and March 2022. Functional evaluation was performed in all patients 3 months after reconstruction (where the patients required no adjuvant radiotherapy) or after radiotherapy. Total flap necrosis was seen in 5 patients with free flap reconstruction (2 radial forearm flaps, 1 lateral arm flap, and 2 anterolateral thigh flaps), 5 patients with infrahyoid myocutaneous flap, and 1 patient reconstructed with a supraclavicular flap. Our success rate is 96.6%; partial flap necrosis was observed in 11 patients with infrahyoid myocutaneous flap and 2 patients with a supraclavicular flap. Most patients with subtotal glossectomy or smaller defects (type II-IVA defects) could communicate on the phone and had the near-normal capacity for an oral diet. The remaining patients (type IVB-V defects) had significantly lower speech scores. The majority of patients could eat liquid and semiliquid foods. Tongue cancer surgery and subsequent reconstruction posed exciting challenges for the surgeon to optimize tongue function and quality of life for patients. Attention to the principles of tongue reconstruction and choosing appropriate flap for each defect achieve better functional results.

Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice.

Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities.

Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer

Occult lymph-node metastasis is a crucial predictor of tongue cancer mortality, with an unmet need to understand the underlying mechanism. Our immunohistochemical and real-time PCR analysis of 208 tongue tumors show overexpression of Matrix Metalloproteinase, MMP10, in 86% of node-positive tongue tumors (n = 79; p < 0.00001). Additionally, global profiling for non-coding RNAs associated with node-positive tumors reveals that of the 11 significantly de-regulated miRNAs, miR-944 negatively regulates MMP10 by targeting its 3’-UTR. We demonstrate that proliferation, migration, and invasion of tongue cancer cells are suppressed by MMP10 knockdown or miR-944 overexpression. Further, we show that depletion of MMP10 prevents nodal metastases using an orthotopic tongue cancer mice model. In contrast, overexpression of MMP10 leads to opposite effects upregulating epithelial-mesenchymal-transition, mediated by a tyrosine kinase gene, AXL, to promote nodal and distant metastasis in vivo. Strikingly, AXL expression is essential and sufficient to mediate the functional consequence of MMP10 overexpression. Consistent with our findings, TCGA-HNSC data suggests overexpression of MMP10 or AXL positively correlates with poor survival of the patients. In conclusion, our results establish that the miR-944/MMP10/AXL- axis underlies lymph node metastases with potential therapeutic intervention and prediction of nodal metastases in tongue cancer patients.

A Systemic and Integrated Analysis of p63-Driven Regulatory Networks in Mouse Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and is linked to tobacco exposure, alcohol consumption, and human papillomavirus infection. Despite therapeutic advances, a lack of molecular understanding of disease etiology, and delayed diagnoses continue to negatively affect survival. The identification of oncogenic drivers and prognostic biomarkers by leveraging bulk and single-cell RNA-sequencing datasets of OSCC can lead to more targeted therapies and improved patient outcomes. However, the generation, analysis, and continued utilization of additional genetic and genomic tools are warranted. Tobacco-induced OSCC can be modeled in mice via 4-nitroquinoline 1-oxide (4NQO), which generates a spectrum of neoplastic lesions mimicking human OSCC and upregulates the oncogenic master transcription factor p63. Here, we molecularly characterized established mouse 4NQO treatment-derived OSCC cell lines and utilized RNA and chromatin immunoprecipitation-sequencing to uncover the global p63 gene regulatory and signaling network. We integrated our p63 datasets with published bulk and single-cell RNA-sequencing of mouse 4NQO-treated tongue and esophageal tumors, respectively, to generate a p63-driven gene signature that sheds new light on the role of p63 in murine OSCC. Our analyses reveal known and novel players, such as COTL1, that are regulated by p63 and influence various oncogenic processes, including metastasis. The identification of new sets of potential biomarkers and pathways, some of which are functionally conserved in human OSCC and can prognosticate patient survival, offers new avenues for future mechanistic studies.

Intra-operative intaoral ultrasonograpy ensures free deep resection margins in carcinoma tongue: A pilot study.

Resection of primary in carcinoma tongue is challenging as the tumor often spreads submucosal and deep in muscles. There are various Intraoperative tools available to guide tumor resection margins. We studied the use of intraoperative ultrasound-guided resection for obtaining free deep resection margins in cases of oral carcinoma tongue. To assess the feasibility of resection of tongue tumor using intraoral ultrasound intraoperatively. 5 patients of oral tongue squamous cell carcinoma were included in this prospective pilot study. Intraoral ultrasound-guided resection of the primary tongue tumor was done. The surgeon moved the probe over the tumor and focussed on the point of maximum invasion by the tumor. A 26 G needle was passed in the tongue at a point that was 10 mm away from the deepest point of infiltration. It marked the deepest plane of resection. Following the above marking, a resection of tumor was done. Deep surgical resection margin was found to be >5 mm (free) in all the USG-guided surgically resected primary tongue tumors on histopathological examination. We have found intraoperative ultrasonography a useful tool for the surgical resection of primary tongue tumours.

Vascular and Neural Invasion in Oral Squamous Cell Carcinoma: A Study in an Iranian Population.

Among various parameters used to predict the outcome of malignancy, nerve invasion has been widely considered as a sign of aggressive behavior in oral cancers. According to the importance of neural invasion in predicting the outcome of oral squamous cell carcinoma (OSCC), this study aimed to evaluate the prevalence of neural and vascular invasion in OSCC. In this descriptive, analytical, and cross-sectional study, paraffin-embedded tissues of 62 OSCC in the health center of surgery and pathology were evaluated (2013-2015). Patients' archives were evaluated and recorded in terms of their age and gender. Hematoxylin and eosin (H&E) slides were then examined by two oral pathologists and scrutinized for the presence of nerve involvement, tumor differentiation, vascular and lymph node invasion, and depth of invasion. Data were analyzed using SPSS version 23, t-test, and one-way ANOVA (P < 0.05). Of 62 tumors, 12 patients showed only nerve invasion, 17 cases had only vascular invasion, and seven patients had both neural and vascular invasion, simultaneously, known as a neurovascular invasion. Furthermore, there was no vascular and neural invasion in 26 cases. There was a statistically significant correlation between vascular and neural invasion and the tumor site (P = 0.045). The highest frequency of neural invasion, as well as vascular invasion, was related to tongue tumors. The relation between neural and vascular invasion in OSCC with tumor's location was statistically significant. Lip and tongue carcinoma had shown more neurovascular invasion without relation to gender, age, and cell differentiation.

Novel cancer associated fibroblasts from diverse locales enhance the tumorigenicity of tongue tumor epithelia

Novel cancer associated fibroblasts from diverse locales enhance the tumorigenicity of tongue tumor epithelia

The chemotherapeutic activity of areca nut extract increased stromal tumor-infiltrating lymphocytes in 4-nutriquinoline-1-oxide-tumor-induced Sprague-Dawley rats

Background: Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers with a high mortality rate. The biodiversity source in Indonesia makes areca nut a potential antioxidant in treating disease. Objective: The study aimed to evaluate the chemotherapeutic effect of areca nut extract in 4-nutriquinoline-1-oxide (NQO)-tumor-induced rats. Methods: Twenty-eight male Sprague-Dawley rats were divided into four groups. Group 1 served as the control group, group 2 was 4NQO-induced rats without treatment, and groups 3 and 4 were given 4NQO-tumor inducer with 500 and 1000 mg/kg BW of areca nut extract, respectively. The rats in groups 2,3, and 4 received 30 ppm of 4NQO tumor inducer in drinking water for 12 weeks. In the end, all rats were euthanized and the tongue was removed. The body, liver, kidney, heart, and lungs weights were measured. Tongue tumor volume and dysplasia lesions were analyzed. The tumor-infiltrating lymphocytes (TILs) in the tumor and stromal area were scored semi-quantitatively associating the infiltrate grade (0-3) and analyzed histologically. Results: There were significant differences in body weight loss between the initial and final phases in groups 1 and 2 (p&lt;0.05). The areca nut at doses of 500 and 1000 mg/kg BW significantly reduced the tumor size compared with groups 1 and 2 (p&lt;0.05). The incidence of OSCC in rats with 500 and 1000 mg/kg BW of areca nut extract after 22 weeks was 0%, but the dysplasia lesions were observed at 28.57% and 85.71%, respectively. The highest mean of stromal TILs was in group 3 and there were significant differences in stromal TILs between groups 2 and 3 (p&lt;0.05). Conclusion: Areca nut extract exerts a chemotherapeutic activity in 4NQO-induced rats by inducing infiltrating lymphocytes in the stromal tumor area on the OSCC lesion of the tongue.

No survival benefit in never-smoker never-drinker patients with oral cavity cancer.

Although strongly associated with tobacco and alcohol use, many oral cavity squamous cell carcinoma (OCSCC) cases occur in patients without exposure to either, known as "never-smoker, never-drinkers" (NSND). We aimed to compare clinical outcomes between NSND and tobacco/alcohol-exposed populations and to define demographic characteristics of NSND. We performed a retrospective, single-institution cohort study of 672 OCSCC patients. Cox models were used to estimate differences in overall survival (OS) and recurrence-free survival (RFS) between NSND and tobacco/alcohol-exposed patients while adjusting for confounders. NSND represented 25.6% of our cohort and were older, more female, and more economically advantaged. Among NSND, oral tongue tumors dominated in younger patients, while alveolar ridge tumors dominated in elderly patients. Multivariate survival analysis revealed no differences in OS or RFS between NSND and tobacco/alcohol-exposed patients. When adjusted for independent biologic features, clinical outcomes in OCSCC are similar between NSND and tobacco/alcohol-exposed patients.

Use of transoral ultrasonography technique in tongue cancer: Advantages and disadvantages

Aim. To evaluate advantages and disadvantages of transoral ultrasonography (US) in tongue cancer.Materials and methods. US was performed in 165 patients between the ages of 15 and 85 years with malignant tumors of the mobile tongue (74 (44.9 %) women, 91 (55.1 %) men).Among 165 patients, 144 had primary tongue tumor. The study also included 21 (12.7 %) patients with recurrent tumor which clinically could be represented by a true recurrence (tumor development 6 months after the end of treatment) or by continued growth (tumor development less than 6 months after the end of treatment). The study included patients with tongue tumors Т1 - 50 (30.3 %) patients, Т2 - 78 (47.3 %) patients, Т3 - 16.4 % of patients, Т4 - 6.1 % of patients.Three types of approach to tongue tumor visualization were used: submandibular, transoral, and transbuccal with a standard linear transducer (4-9 MHz) and intraoperative linear transducer (5-14 MHz). In total in 165 patients with tongue tumors, 147 (89.1 %) transoral US, 86 (52.1 %) submandibular US and 25 (15.2 %) transbuccal US examinations were performed.Results. Among 165 patients, agreement between the sizes measured using US and histological examination was observed in 142 (86.1 %) patients taking into account 15 % error.With increasing tumor thickness and, correspondingly, T criterion, increased frequency of agreement between US data and histological data was observed. Thus, for T1 stage frequency of agreement with US data was observed in 61.8 % of cases, for Т2 stage in 81.1 % of cases, for Т3 stage in 93.8 %, and for Т4 stage agreement was observed in 100 % of cases.Frequency of agreement with histological data in evaluation of tongue tumor thickness for transoral approach was significantly higher than for submandibular approach (р = 0.014). Transoral technique was more accurate for measurement of thickness of primary tumors - 80.3 % of results agreed with histological examination, and for recurrences frequency of agreement was only 33.3 %. Submandibular approach for primary tumors showed accurate measurements only in 67.6 % of cases, in recurrent tumors in 58.3 % of cases. Transbuccal approach also showed higher measurement accuracy for tumor thickness in primary patients (70.0 %) compared to recurrent tumors (40.0 %).Conclusion. Use of transoral ultrasonography significantly improves clinical staging of tongue tumors at the preoperative stage.

Clinical features and therapeutic outcomes of alveolar soft part sarcoma in children: A single-center, retrospective study.

Alveolar soft part sarcoma (ASPS) is a rare sarcoma that has been shown to be highly effective to antiangiogenic agents and immune checkpoint inhibitors, but most reported studies about ASPS were concentrated on adult population. In this study, we aimed to describe the clinical features and therapeutic outcomes of ASPS in children. We retrospectively reviewed the records of patients with ASPS in our institution since Jan 2015. All patients included in this study were pathologically confirmed ASPS and aged under 12 years at the time of initial diagnosis. Demographic characteristics, tumor sizes, primary tumor sites, metastasis, treatments used, therapeutic responses and survivals were evaluated. We identified a total of 56 patients to be initially diagnosed as ASPS since Jan 2015.A predisposition of high occurrence in head and neck (32.1%) was observed (versus 41.1% in limbs and 21.4% in trunk). 26 (46.4%) patients developed metastasis at the time of diagnosis or during follow-up. Tumors in tongue, pharynx and larynx had the least likelihood to metastasize (7.7%, P<0.05). Observation was recommended for 15 stage IV patients with only pulmonary metastasis. 7 (46.7%) patients remained stable until last follow up. The 1-year PFS rate was 83.3% and median progression-free survival time (PFS) was 29.4 months. 15 patients with progressive disease received mono or combined therapy. 11 patients received PD-1 monotherapy. 2 patients achieved partial response and 5 stable disease. The overall response rate was 18.2%. The median PFS of this group was 22.0 months, and the 1-year PFS rate was 70.0%. 4 patients received a combination therapy of PD-1 inhibitors plus tyrosine kinase inhibitors. All of them remained stable. No disease-related death occurred during follow-up. ASPS exhibits a higher occurrence in head and neck in children. ASPS originating from glossopharyngeal region tends to have a lower metastasis rate. ASPS displays a more indolent growth pattern in children, which makes observation a preferable choice for children with sole pulmonary metastasis. Pediatric ASPS appears to be less effective to targeted therapy and immunotherapy than adults. The treatment of progressive ASPS in children remains challenging.

Own experience of surgical treatment for advanced cancer of the tongue and the mouth floor

Purpose of the study. Improvement of surgical treatment outcomes in patients with advanced cancer of the tongue and the mouth floor providing radical surgery with preservation of the organ functions.Materials and methods. Two patients with advanced cancer of the tongue and the mouth floor with metastases to lymph nodes in the neck (St.4 (IVA, рT4a N2b M0), clinical group 2, were operated on according to our special technique. The surgery was performed under endotracheal anesthesia. After cervical lymph node dissection, the tongue and the mouth floor tissues were resected intraorally. The incisions were made through their entire thickness along healthy tissues. Smears were taken from the dissected tissues for intraoperative pathology consultation control for the presence of cancer cells. The tissues of the mouth floor affected by the tumor were completely removed without going beyond the hyoglossus muscle, since the lingual and hypoglossal nerves go along its outer surface. This allowed radical tumor removal with preservation of the tongue functions.Results. Patients operated on according to our special technique have been observed for more than 9 months without continued tumor growth and recurrences tumor with preservation of the tongue and the mouth floor functions.Conclusion. In such patients, ablastics principles are combined with the preservation of the tongue functions. This can be achieved because after removal of the tongue tumor, resection of the mouth floor is performed without going beyond the hyoglossus muscle not affected by the tumor, since the lingual and hypoglossal nerves go along its outer surface. Complying with ablastics, it preserves the tongue functions: chewing, swallowing, articulate speech, taste perception.

Prevalence of Human Papillomavirus and Co-Infection with Epstein-Barr Virus in Oral and Oropharyngeal Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma is one of the most important malignancies, worldwide. Oncogenic viruses, such as human papilloma virus (HPV) and Epstein-Barr virus (EBV), are linked to these cancers and studies suggest a possible interaction between HPV and EBV during co-infections to promote oncogenesis. Nonetheless, these reports are controversial and demand more investigations in this regard. The present work to assessed the prevalence of HPV and co-infection with EBV in oral and oropharyngeal squamous cell carcinomas. Formalin-fixed paraffin-embedded tissues were collected from 166 archived oral and oropharyngeal squamous cell carcinoma samples from Ahvaz Imam Khomeini hospital, Ahvaz, Iran, from March 2013 and December 2019. Nested-PCR was used to detect the viruses and type-specific PCR/nested-PCR and sequencing were performed for virus genotyping. Out of the 166 specimens, 84.33% and 16.42% were from oral cavity and oropharynx, respectively; of which, 32 cases (19.3%) were HPV-positive (16.42% of oral cavity and 34.6% of oropharynx). HPV was detected in 36.36%, 25%, and 16.42% of base of tongue, tonsil, and oral tongue tumors, respectively. HPV was more associated with well differentiated tumors (24;18.04%) in compared to moderately and poorly differentiated ones. Regarding HPV-16 genotyping, 7 (21.8%) out of the 32 samples were found to be HPV-16 (4/26 (15.38%) for oropharynx and 3/140 (2.14%) for oral cavity). Moreover, 90 samples were evaluated for EBV infection and co-infection; of which, 4 (4.4%) subjects tested positive for EBV, including two cases with HPV co-infection. All the positive cases were EBV type B, from oral cavity, and histologically well differentiated. HPV was more associated with oropharyngeal cancer. This association has been linked to various factors such as repeated oral and oropharyngeal exposure to HPV due to change in patterns of sexual behaviors; a phenomenon that may demand routine HPV vaccination.

MRI findings of benign tumors and tumor-like diseases of the tonguewith radiologic-pathologic correlation.

Benign tumors or tumor-like lesions of the tongue are uncommon lesions that comprise a heterogeneous group of neoplasms. Although there are a variety of benign tumors or tumor-like lesions, the imaging appearance of these diseases is not well defined because of a paucity of scientific literature on this topic. Most benign tongue tumors usually appear as submucosal bulges located in the deep portion of the tongue. Their true features and extent may only be identified on cross-sectional images such as CT and MRI. Thus, CT and MRI play an important role in the diagnosis of these unusual lesions. It is important that radiologists be able to identify the characteristic CT and MR imaging features that can be used to narrow the differential diagnosis with increased diagnostic confidence, suggest specific histologic tumor types. In this pictorial essay, we provide insights into the MRI presentations of benign tongue tumors and tumor-like diseases and their radiologic-pathologic correlation. Benign tumors or tumor-like lesions of the tongue described herein include papilloma, lipoma, hemangioma, venous malformations, schwannoma, neurofibroma, epidermoid cyst, and dermoid cyst.

Influence of Site, Size, Depth of Invasion and Histologic Grading on the Occurrence of Cervical Level IIb Metastasis and Extranodal Extension in Clinically N0 Neck of Patients with OSCC: A Single Center Retrospective Analysis.

Depth of Invasion ≥ 4mm, T stage and primary site with more than 20% chances for occult metastasis are currently the accepted indications for elective neck dissection. Nodal metastasis decreases survival by 50%. ENE further reduces the prognosis. Dissection of level IIb lymph nodes in clinically N0 neck does not improve survival. A total of 320 patients were evaluated. Binary and multiple logistic regression and chi-square test were used for data analysis. ROC curve with Youden's J index was used to set up a cutoff value for DOI. The predictor variables were site, size, grading and depth of invasion of primary tumor. Incidence of level IIb metastasis and ENE were the outcomes. The study revealed a significant association and risk stratification between primary tumor characteristics with the occurrence of ENE. The cutoff value for DOI predicting ENE was 12.5mm. Tumors of the oral tongue were an independent risk factor for level IIb metastasis. Size of primary tumor, DOI, tumors of the mandibular alveolus and poor grading are independent risk factors for ENE. Isolated metastasis to level IIb rarely occurs in the absence of concomitant level IIa metastasis. Size, DOI and grading were significantly associated with level IIb metastasis. However, only tumors of the oral tongue were independent risk factor.

Tongue cancer tailored photosensitizers for NIR-II fluorescence imaging guided precise treatment

Although several photosensitizers have been used for photodynamic therapy (PDT) of tongue cancer, the treatment efficacy was still suffered from the short excitation wavelength of photosensitizer, low reactive oxygen species (ROS) yield in hypoxic tumor microenvironment and lack of monitoring method. Herein, by introducing two electron - deficient groups (A) on D-A′-D core, a novel near-infrared II (NIR-II) molecule with A-D-A′-D-A configuration is developed. Via the rational design of molecular structure, NIR-II molecule exhibits excellent properties: i) The intramolecular multiple “push-pull” interactions and the enlargement of conjugated system results in the absorption wavelength red-shift, so that the photosensitizers could be effectively excited by NIR laser (808 nm). ii) The reduced ΔEST promotes the intersystem crossing (ISC) process and enables high-efficient generation of ·OH via Type I PDT, addressing the limitation of hypoxic tumor. iii) The high emission of NIR-II fluorescence and excellent optical stability endow the repeated NIR-II imaging to report the precise localization of tongue tumor for guiding laser irradiation and monitoring treatment, so as to achieve precise dose and timing of administration and minimize the side effect. Therefore, this work will provide insights into design of tongue cancer tailored photosensitizers for precise and effective therapy.