De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Distant metastasis at the time of presentation of head and neck squamous cell carcinoma: a retrospective chart review from a tertiary cancer care centre.

OBJECTIVE: To evaluate the rates and patterns of distant metastasis in head and neck SCC at the time of presentation and to study the association between distant metastasis with pre-treatment, clinical, and pathological predictors of outcomes. METHOD: This is a retrospective study conducted in a tertiary care hospital. All patients with primary head and neck squamous cell carcinoma that had been evaluated at our institute between October 2018 and December 2020 were included in the study. Various clinical data were analysed and pattern of metastasis was studied. RESULT: Ten per cent (50 cases) of 501 studied patients had distant metastasis. The most common site of distant metastasis was lung. The rate of distant metastasis was high in patients with poorly differentiated cancers. By Kaplan-Meier analysis, the median survival duration after diagnosis of metastasis was four months. CONCLUSION: The rate of distant metastasis was 10 per cent in the study. Patients with poorly differentiated tumours, locally advanced primary lesions, higher nodal stage, particularly with extra nodal extension, and hypopharyngeal primary, tend to exhibit increased risk for distant metastasis at the time of presentation.

The impact of LncRNA-SOX2-OT/let-7c-3p/SKP2 Axis on head and neck squamous cell carcinoma progression: Insights from bioinformatics analysis and experimental validation.

BACKGROUND: LncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) is linked to multiple cancers, but its specific role and mechanism in head and neck squamous cell carcinoma (HNSCC) remain poorly understood. METHODS: We harnessed clinical data and HNSCC transcriptome profiles from UCSC Xena, TCGA, and GEO databases. Employing various algorithms, we assessed the correlation between SOX2-OT expression and the HNSCC immune microenvironment. Differential expression analysis identified immune-enriched miRNAs (DEmiRNAs) and mRNAs (DEmRNAs). Utilizing miRanda, miRWalk, and Cytoscape, we constructed a ceRNA network encompassing SOX2-OT, DEmiRNAs, and DEmRNAs. A Sankey diagram visualized pivotal SOX2-OT-miRNA-mRNA-pathways. Functional assays validated SOX2-OT silencing effects in HNSCC cells. Luciferase reporter assays verified SOX2-OT/let-7c-3p/SKP2 relationships. Additionally, a xenograft mouse model revealed SOX2-OT's impact on xenograft growth and lung metastasis. RESULTS: SOX2-OT expression demonstrated a predominantly positive correlation with B lineage and VTCN1, while manifesting a negative correlation with Neutrophil and CD47 in HNSCC tissues. We discerned a ceRNA network comprising 65 DEmiRNAs and 116 DEmRNAs, while a protein-protein interaction (PPI) network revealed 97 protein nodes among DEmRNAs. Notably, the Sankey diagram spotlighted six key DEmRNAs intricately linked to the SOX2-OT-regulated DEmiRNAs immune-related pathway. Experimental assays established that SOX2-OT silencing exerted inhibitory effects on cell proliferation, migration, tumor growth, and lung metastasis within HNSCC cells, both in vitro and in vivo. We identified let-7c-3p as a target miRNA of SOX2-OT and SKP2 as a target mRNA of let-7c-3p. CONCLUSIONS: Our study establishes the critical SOX2-OT/let-7c-3p/SKP2 axis as a pivotal regulator of HNSCC tumorigenesis and metastasis.

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC). PATIENTS AND METHODS: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases. RESULTS: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively. CONCLUSION: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future.

Diagnostic Value of MRI Combined with CXCR4 Expression Level in Lymph Node Metastasis Head and Neck Squamous Cell Carcinoma.

Objective: To explore the diagnostic value of magnetic resonance imaging (MRI) combined with CXCR4 expression levels in lymph node metastasis of the head and neck squamous cell carcinoma (HNSCC). Methods: 289 patients with HNSCC were divided into lymph node metastasis group (LNM group, n = 171) and non-LNM group (n = 118) according to the pathological examination results. MRI was used to scan the patient's lesions and cervical lymph nodes, and ADC was measured by MRI diffusion weighting imaging. The expression of CXCR4 in tumor tissues was detected by qRT-PCR. Logistic regression was used to analyze the risk factors of HNSCC lymph node metastasis. ROC curve was used to analyze the diagnostic effects of MRI, CXCR4, and MRI combined with CXCR4 on HNSCC lymph node metastasis. Results: Compared with the non-LNM group, patients in the LNM group had a lower degree of pathological differentiation, and the positive rate of TNM staging and vascular invasion was higher. The signal intensity of T1WI and T2WI were low intensity and high intensity, respectively, and the ADC value was significantly reduced. At the same time, the expression level of CXCR4 in the tumor tissues of the LNM group was also significantly increased. In addition, compared with MRI and CXCR4 used alone, MRI combined with CXCR4 has a higher predictive value. Conclusion: MRI has a good effect in demonstrating lymph node metastasis. CXCR4 is significantly upregulated in lymph node metastasis tumor tissue. The combination of the two can be used for clinical diagnosis of HNSCC lymph node metastasis.

G-Protein-Coupled Receptor Kinase-Interacting Protein 1 (GIT1) Promotes Head and Neck Squamous Cell Carcinoma Metastases via Activating the PI3K/AKT/mTOR Signal Pathway.

OBJECTIVE: GIT1 is identified as a novel tumor oncogene in breast cancer. In this article, we aimed to explore the role of GIT1 in the progression of head and neck squamous cell carcinoma (HNSCC). METHODS: GIT1 expression in HNSCC was detected by RT-qPCR, immunohistochemistry assay, and Western blot. HNSCC cell proliferation, migration, and invasion were examined by CCK-8 assay, Wound healing assay, and Transwell assay, respectively. Cell apoptosis was detected by flow cytometric analysis. RESULTS: In our study, GIT1 was notably upregulated in HNSCC tissues and cells. Moreover, GIT1 expression level had positive corelation with pathological grade and nodal status of HNSCC. Functional experiments showed that knockdown of GIT1 restrained HNSCC proliferation, invasion, migration, and EMT and facilitated cell apoptosis. Furthermore, GIT1 knockdown was found to restrain HNSCC tumor growth and lung metastasis. Additionally, PI3K/AKT/mTOR signal pathway inhibitors suppressed the effect of GIT1 on HNSCC cell progression. CONCLUSION: GIT1 was upregulated in HNSCC and facilitated HNSCC cell progression by inducing PI3K/AKT/mTOR signal pathway. Therefore, we suggested that GIT1 might be a potential target for HNSCC treatment.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma.

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

PD-L1 Expression and Survival Rates Using TPS and CPS for Nivolumab-treated Head-and-Neck Cancer.

BACKGROUND/AIM: This study investigated the expression and survival rates of programmed cell death ligand 1 using the tumor proportion score (TPS)and combined positive score (CPS) for recurrent/metastatic head and neck cancer administered nivolumab. PATIENTS AND METHODS: Forty-seven patients with recurrent/metastatic head and neck cancer with a history of platinum-based chemotherapy who received nivolumab between June 1st, 2017, and January 31st, 2019 were included in this study. RESULTS: TPS and CPS were strongly correlated (r=0.546). When the TPS was high (≥40%), overall and progression-free survival were significantly better. The median overall survival was 8.5 months, median progression-free survival was not reached, and the 1-year progression-free survival rate was 71.4%. However, there was no significant difference in overall and progression-free survival between the groups with high CPS (≥20). CONCLUSION: This is the first report to show a strong correlation between TPS and CPS. High TPS (40% or higher) may be used as a predictor of prognosis and efficacy. Further studies are warranted to determine the use of the CPS as a biomarker.

Comparison of Dosage of Nivolumab in Efficacy and Safety for Recurrent Metastatic Squamous Cell Carcinoma.

BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.

Intra-arterial chemotherapy targeting metastatic cervical lymph nodes in head and neck cancer.

BACKGROUND: Large cervical lymph nodes and the extranodal extension of metastatic lymph nodes are considered poor prognostic factors in head and neck squamous cell carcinoma (HNC). AIMS/OBJECTIVES: The efficacy of intra-arterial chemotherapy (iaCT) targeting lymph node (LN) in HNC was examined. MATERIALS AND METHODS: We performed a retrospective review of 41 patients with laryngeal and hypopharyngeal cancer showing metastatic cervical LN larger than 20 mm treated with iaCT with concurrent radiotherapy. The administration of cisplatin into LN was divided into three groups: no administration (NO), via the same artery as that supplying the primary tumor (SAME), and via a different artery from that supplying the primary tumor (DIFFERENT). RESULTS: A trend toward a more favorable three-year regional control in DIFFERENT compared to NO was observed, although the mean size of LN in DIFFERENT was larger than in the other groups. A better regional control was obtained in both DIFFERENT (p < .05) and DIFFERENT + SAME (p < .05) when overall rather than partial enhancement of lymph node by CT angiography was observed. Extranodal extension could be a factor predicting unfavorable regional control. CONCLUSIONS/SIGNIFICANCE: Targeting lymph node may be helpful to avoid neck dissection when iaCT was planned in HNC with relatively large LNs.

Prognostic Factors of Potential Early Recurrence of Hypopharyngeal Carcinoma.

BACKGROUND/AIM: Prognostic factors of hypopharyngeal carcinoma have been reported previously. However, recurrent cases of this disease occurring within 6 months of treatment have been excluded or poorly documented in many studies. We aimed to evaluate the prognostic factors of hypopharyngeal carcinoma recurrence within 6 months. PATIENTS AND METHODS: A total of 120 patients were eligible for this retrospective study. Recurrent cases of hypopharyngeal carcinoma occurring within 6 months of treatment were evaluated and compared with non-recurrent cases. RESULTS: Recurrence within 6 months was detected in 28/50 cases. In univariate analyses, classification markers (pT≥4a and cN≥2b) were statistically significant prognostic factors for early recurrence (p=0.04 and p=0.04, respectively); however, only pT≥4a was predictive of recurrence in multivariate analyses (p=0.02). CONCLUSION: Risk stratification according to the prognostic factor pT≥4a will allow physicians to identify patients who should be followed meticulously within the first 6 months.

Multicenter Retrospective Study of Weekly Cetuximab Plus Paclitaxel for Recurrent or Metastatic Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study was conducted to compare the efficacy and safety of the weekly cetuximab plus paclitaxel (wCmab-PTX) regimen with those of the EXTREME regimen in patients with recurrent or metastatic oral squamous cell carcinoma (R/M OSCC). PATIENTS AND METHODS: This multicenter retrospective study involved a chart review of the clinical records of R/M OSCC patients treated with wCmab-PTX in each institution between January 2013 and December 2017. Data were collected, and the efficacy, safety, and treatment outcomes were analyzed. RESULTS: The best overall response and disease control rates were 48.4% and 61.3%, respectively. The median PFS and OS were 6 and 13 months, respectively. There was no significant difference in prognosis with or without previous platinum administration. The grade 3-4 adverse events were leukopenia (16.1%), followed by acne-like rash (12.9%), and neutropenia (9.7%). All adverse events, excluding more than grade 3 infusion reactions, were tolerable and manageable. CONCLUSION: wCmab-PTX may be considered as a treatment option for R/M patients with OSCC that is refractory to platinum-based chemotherapy, or progressive disease after receiving chemotherapy.

A priori quality assurance using a benchmark case of the randomized phase 2 GORTEC 2014-14 in oligometastatic head and neck cancer patients.

PURPOSE: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. MATERIAL AND METHODS: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. RESULTS: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. CONCLUSION: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody Cetuximab via Combination With Natural Killer Cell Chartering Immunotherapeutic Strategies.

Cetuximab has an established role in the treatment of patients with recurrent/metastatic colorectal cancer and head and neck squamous cell cancer (HNSCC). However, the long-term effectiveness of cetuximab has been limited by the development of acquired resistance, leading to tumor relapse. By contrast, immunotherapies can elicit long-term tumor regression, but the overall response rates are much more limited. In addition to epidermal growth factor (EGFR) inhibition, cetuximab can activate natural killer (NK) cells to induce antibody-dependent cellular cytotoxicity (ADCC). In view of the above, there is an unmet need for the majority of patients that are treated with both monotherapy cetuximab and immunotherapy. Accumulated evidence from (pre-)clinical studies suggests that targeted therapies can have synergistic antitumor effects through combination with immunotherapy. However, further optimizations, aimed towards illuminating the multifaceted interplay, are required to avoid toxicity and to achieve better therapeutic effectiveness. The current review summarizes existing (pre-)clinical evidence to provide a rationale supporting the use of combined cetuximab and immunotherapy approaches in patients with different types of cancer.

Long non-coding RNAs orchestrate various molecular and cellular processes by modulating epithelial-mesenchymal transition in head and neck squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) regulate various hallmarks associated with the progression of human cancers through their binding with RNA, DNA, and proteins. Epithelial-Mesenchymal Transition (EMT) is a cardinal and multi-stage process where epithelial cells acquire a mesenchymal-like phenotype that is instrumental for tumor cells to initiate invasion and metastasis. LncRNAs can potentially promote tumor onset and progression as well as drug resistance by directly or indirectly altering the EMT program. Head and neck squamous cell carcinoma (HNSCC) are a dreadful malignancy affecting public health globally. The past few years have provided a better insight into the mechanism of EMT in HNSCC. The differential expression of the lncRNAs that can act either as promoters or suppressors in the process of EMT is of great importance. In this review, we aim to sum up, the highly structured mechanism with the diverse role of lncRNAs and their interaction with different molecules in the regulation of EMT. Moreover, discussing principal EMT pathways modulated by lncRNAs and their prospective potential value as therapeutic targets.

Overexpressed HGF promotes metastasis of squamous cell carcinoma of the head and neck through the PI3K/Akt and JNK signaling pathways.

Background: The role of HGF in squamous cell carcinoma of the head and neck (SCCHN) is not clear. Methods: Reverse transcription PCR, western blotting, gelatin zymography, immunohistochemistry, actin polymerization, chemotaxis and migration assays were used in the authors' study. Results: HGF expression level was upregulated in SCCHN cells, which was associated with clinical stage; tumor, node, metastasis classification; and lymphatic invasion. SCCHN cells with high Met expression were sensitive to cell invasion, which was blocked by inhibiting PI3K/Akt and JNK. HGF induced MMP9 expression and enhanced its activity. Akt induced the activation of JNK through the PI3K/Akt and JNK signaling pathways. Conclusion: HGF upregulates MMP9 through the activation of the PI3K/Akt and JNK signaling pathways in SCCHN cells.

First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial.

BACKGROUND: The EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. METHODS: Patients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). RESULTS: Overall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40-0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50-0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. CONCLUSIONS: CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. CLINICAL TRIAL REGISTRATION NUMBER: NCT02383966.

TRIM21 Polymorphisms are associated with Susceptibility and Clinical Status of Oral Squamous Cell Carcinoma patients.

Squamous cell cancer of head and neck (HNSCC) is the sixth most common malignancy worldwide. One of the most common HNSCC types is oral squamous cell carcinoma (OSCC), which is the fifth leading cause of cancer death in Taiwan. Tripartite motif 21 (TRIM21) has been reported to play an important role in different cancer types. We found a correlation between TRIM21 and survival of HNSCC patients, but little information exists about how altered TRIM21 expression contributes to tumorigenesis. Thus, we investigated the combined effect of TRIM21 polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of OSCC. Two single-nucleotide polymorphisms (SNPs) of TRIM21 (rs4144331, rs915956) from 1194 healthy controls and 1192 OSCC patients were analyzed by real-time PCR. Among 1632 smokers, TRIM21 polymorphism carriers with the betel-nut chewing habit had a ~4.8-fold greater risk of OSCC than TRIM21 wild-type carriers without the betel-nut chewing habit. After adjusting for other covariants, OSCC patients with G/T at TRIM21 rs4144331 had a high risk for distant metastasis compared with G/G homozygotes. This study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development. Thus, our findings suggest that this study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development and suggest that interactions between mutant genes may alter the susceptibility to OSCC.

Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes.

Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote tumor relapse where the immune-suppressive tumor microenvironment (TME) could be instrumental. We established a novel syngeneic grafting model from a carcinogen-induced tongue tumor, OSCC13, to address the impact of radiotherapy on OSCC. This model revealed similarities with human OSCC, recapitulating carcinogen-induced mutations found in smoking associated human tongue tumors, abundant tumor infiltrating leukocytes (TIL) and, spontaneous tumor cell dissemination to the local lymph nodes. Cultured OSCC13 cells and OSCC13-derived tongue tumors were sensitive to irradiation. At the chosen dose of 2 Gy mimicking treatment of human OSCC patients not all tumor cells were killed allowing to investigate effects on the TME. By investigating expression of the extracellular matrix molecule tenascin-C (TNC), an indicator of an immune suppressive TME, we observed high local TNC expression and TIL infiltration in the irradiated tumors. In a TNC knockout host the TME appeared less immune suppressive with a tendency towards more tumor regression than in WT conditions. Altogether, our novel syngeneic tongue OSCC grafting model, sharing important features with the human OSCC disease could be relevant for future anti-cancer targeting of OSCC by radiotherapy and other therapeutic approaches.

Epidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation.

Metastasis of oropharyngeal squamous cell carcinoma (SCC) to skin is uncommon and portends a poor prognosis. Clinical history and histopathology are key to discerning between metastatic disease vs de novo SCC of the skin. We describe a case of an HPV+ tonsillar SCC in a 77-year-old male, with metastasis to the neck skin. This case is unique because of prominent in situ epidermal involvement on skin biopsy specimen, complicating the distinction between primary and secondary disease. The nature of the lesion was resolved using next-generation sequencing of both the primary oropharyngeal SCC and skin lesion biopsy specimens. Both tumors showed identical ATR D1639G somatic mutations, while the skin lesion contained an additional POLE F1366L mutation. Clonal evolution of metastatic lesions is a well-described phenomenon; comparing the genetic profiles of primary and metastatic specimens can be useful in evaluating the tumor origin as well as identifying targetable genetic aberrations.