Hypopharyngeal Squamous Cell Carcinoma Research Articles

The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma.

BackgroundThe current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems.ResultsPositive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models.ConclusionsA positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.

The Prognostic Capacity of Systemic Inflammation Response Index, Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in Patients with Hypopharyngeal Squamous Cell Carcinoma

Introduction: Systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been proposed as peripheral blood biomarkers. We compared these blood biomarkers to identify the best predictor in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We conducted a retrospective study on 304 patients with HPSCC. SIRI was divided into three groups using X-tile version 3.6.1. The optimal cut-off points for NLR, LMR, and PLR were selected through RStudio. We compared the prognostic capacity of SIRI with that of NLR, LMR, and PLR using receiver operating characteristic curves. Results: Smoking, cancer in the postcricoid region, lymph node metastasis (N+), extracapsular invasion, SIRI in the highest tertile (>2.80), and LMR in the lowest tertile (<5.0) may cause poor 5-year overall survival (OS) in patients with HPSCC. Local and distant recurrences may occur earlier in those with lymph node metastasis and a tumor invading beyond the mucosa layer. Conclusions: SIRI was a better predictor of OS than LMR, PLR, and NLR in HPSCC patients. SIRI in the highest tertile (>2.80) and LMR in the lowest tertile (<5.0) may cause poor 5-year OS.

Prognostic Value of Pathologically Positive Nodal Number in p16-Negative Oropharyngeal and Hypopharyngeal Squamous Cell Carcinoma with pN3b Status.

In this study, we aimed to investigate the prognostic value of the number of pathologically positive nodes (pN+) in p16-negative oropharyngeal (OPSCC) and hypopharyngeal (HPSCC) squamous cell carcinoma cases with pN3b status after surgery. We reviewed the clinical and pathological features of 120 newly diagnosed p16-negative OPSCC and HPSCC patients with pN3b status after radical surgery. The primary endpoints were the 5-year overall survival (OS), cancer-specific survival (CSS), and their prognostic factors. We used the Cox proportional hazards model for survival analysis. We generated predictive nomograms that incorporated the clinicopathological factors of OS and CSS. The 5-year OS and CSS rates were 44.1% and 59.1%, respectively. The optimal number of pN+ to predict the 5-year OS and CSS was pN+ = 3. In the Cox model, we observed that pN+ ≥ 3 was a significantly negative predictor of OS (HR: 1.9, 95% CI: 1.1–3.2, p = 0.021) and CSS (HR: 2.3; 95% CI: 1.2–4.6; p = 0.015). After adding the pN+ variable, the c-index of the predictive nomogram incorporating assorted clinicopathological factors increased from 0.66 to 0.689 for OS and from 0.713 to 0.75 for CSS. The results highlight the prognostic value of the pN+ number in p16-negative OPSCC and HPSCC patients with pN3b status.

RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6 A-IGF2BP2-dependent manner.

BackgroundHaving emerged as the most abundant posttranscriptional internal mRNA modification in eukaryotes, N6‐methyladenosine (m6A) has attracted tremendous scientific interest in recent years. However, the functional importance of the m6A methylation machinery in ferroptosis regulation in hypopharyngeal squamous cell carcinoma (HPSCC) remains unclear.MethodsWe herein performed bioinformatic analysis, cell biological analyses, transcriptome‐wide m6A sequencing (m6A‐seq, MeRIP‐seq), RNA sequencing (RNA‐seq), and RNA immunoprecipitation sequencing (RIP‐seq), followed by m6A dot blot, MeRIP‐qPCR, RIP‐qPCR, and dual‐luciferase reporter assays.ResultsThe results revealed that ALKBH5‐mediated m6A demethylation led to the posttranscriptional inhibition of NFE2L2/NRF2, which is crucial for the regulation of antioxidant molecules in cells, at two m6A residues in the 3′‐UTR. Knocking down ALKBH5 subsequently increased the expression of NFE2L2/NRF2 and increased the resistance of HPSCC cells to ferroptosis. In addition, m6A‐mediated NFE2L2/NRF2 stabilization was dependent on the m6A reader IGF2BP2. We suggest that ALKBH5 dysregulates NFE2L2/NRF2 expression in HPSCC through an m6A‐IGF2BP2‐dependent mechanism.ConclusionTogether, these results have revealed an association between the ALKBH5‐NFE2L2/NRF2 axis and ferroptosis, providing insight into the functional importance of reversible mRNA m6A methylation and its modulators in HPSCC.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

TIPE2 Inhibits Migration and Promotes Apoptosis as a Tumor Suppressor in Hypopharyngeal Carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) is a common malignant cancer characterized by high metastasis and infiltration. The development of new approaches for the early diagnosis and identification of new therapeutic targets is essential. TIPE2 is well known as a tumor suppressor and related to a favorable prognosis of HSCC. However, its underlying mechanism remains unclear. TIPE2 expression was determined by immunohistochemistry and RT-qPCR. A TIPE2 overexpression stable cell line was generated by lentivirus infection. TIPE2 and other related protein levels were detected by western blotting. The cell cycle and apoptosis were performed by flow cytometric analysis. Cell proliferation was measured with a Cell Counting Kit-8 (CCK-8) assay, and the activity of caspase-3 and caspase-7 was assessed by Caspase-Glo® 3/7 Assay. All data were analyzed with SPSS 25 and GraphPad Prism 8.0. TIPE2 expression was significantly down-regulated in HSCC. Low TIPE2 expression may be associated with poor prognosis in HSCC. TIPE2 overexpression markedly inhibited tumor cell migration. Moreover, TIPE2 decreased cell proliferation but promoted apoptosis. TIPE2 suppressed tumor growth by activating Epithelial-Mesenchymal Transition (EMT) and the extrinsic apoptosis pathway. TIPE2 inhibited tumor progression by suppressing cell migration but promoting apoptosis. TIPE2 can be a new therapeutic target in HSCC.

Costunolide enhances cisplatin-induced cytotoxicity in hypopharyngeal SCC FaDu cells by increasing the production of reactive oxygen species

ObjectiveThe sesquiterpene lactone costunolide (CTL) has attracted much attention due to its antitumor effect on a variety of malignant tumors. However, the effect of CTL on hypopharyngeal squamous cell carcinoma (HSCC) remains unclear. This study aimed to examine the effects of this sesquiterpene lactone on HSCC FaDu cells. MethodsThe FaDu cell line was treated with CTL and/or cisplatin. CCK-8 was used to examine cell viability. Annexin-FITC/PI and Hoechst 33258 staining were used to measure apoptosis. Reactive oxygen species (ROS) were analysed by MitoSOX Red staining. Protein expression was examined by Western blotting. ResultsCTL (0, 2, 4, 6, 8, 10, 20, 30, and 40 µM) dose-dependently induced cytotoxicity in FaDu cells. CTL increased ROS production and induced apoptosis in FaDu cells. Moreover, CTL synergized with cisplatin to induce apoptosis in FaDu cells. In addition, the caspase inhibitor Z-DEVD-FMK attenuated CTL-induced apoptosis. Western blot analysis showed that CTL increased the expression levels of cleaved caspase-3 and Bax and decreased the expression levels of Bcl-2, phospho-AKT and phospho-NF-κB. ConclusionIn conclusion, these data demonstrate that CTL induced apoptosis and enhanced cisplatin-induced cytotoxicity in HSCC FaDu cells.

Significance of induction chemotherapy combined with cetuximab in laryngeal preservation rate of locally advanced hypopharyngeal cancer.

e18078 Background: Anatomical and functional laryngeal organ preservation is critical for patients with locally advanced hypopharyngeal squamous cell carcinoma (LAHSCC). Induction chemotherapy with taxanes (T), cisplatin (P) and 5-FU (F) is a therapeutical option in patients with a strong desire to preserve the throat, whether enhanced induction chemotherapy (TPF/TP combined with cetuximab) can improve laryngeal preservation rate (LPR) and objective response rate (ORR) of LAHSCC remains controversial. Here we report the results of a retrospectively study comparing TPF/TP with TPF/TP plus cetuximab. Methods: Nanfang Hospital database was retrospectively queried for LAHSCC patients who received 2 cycle induction chemotherapy with TPF/TP (paclitaxel, cisplatin, 5-Fu) with or without concurrent use of cetuximab for ORR. Results: A total of 81 patients were identified including 36 which had concurrent use of TPF/TP and cetuximab. The overall ORR was 71.60% (58/81), patients in the TPF/TP +Cetuximab group had significantly improved ORR (83.33% (30/36) vs 62.22% (28/45) (P = 0.037) compared to TPF/TP group. After IC, 24 patients underwent laryngopharyngectomies, 6 underwent larynx-preserving surgeries, 51 underwent CCRT and 3 received salvage surgeries. In addition, the total 3-month laryngeal preservation rate (LPR) was 69.13% (56/81), the cetuximab-associated LPR benefit was observed in patients with 60.0% (27/45) in the TPF/TP group, and 80.56% (29/36) in the TPF/TP +Cetuximab group (P &lt; 0.001). The adverse events of grade 3 or 4 were similar between the two groups except for skin rash (TPF/TP group 6.7% vs TPF/TP+Cetuximab 41.7%, P &lt; 0.001), which gradually subsided within 2 weeks after the drug withdrawal. Conclusions: Concurrent cetuximab use with TPF/TP induction chemotherapy in LAHSCC patients was associated with improved ORR and short-term LPR, with tolerable toxicity. Further prospective evidence from larger trials is warranted.

Cross-comparison of microbiota in the oropharynx, hypopharyngeal squamous cell carcinoma and their adjacent tissues through quantitative microbiome profiling

ABSTRACT Aims To clarify the absolute abundance of microbial communities on hypopharyngeal squamous cell carcinoma and their correlation to those in the oropharynx. Methods Clinical data, swabs, and tissue samples from 27 HPSCC patients were collected in this study and divided into three sampling groups: 19 oropharyngeal mucosa (OPM), 27 hypopharyngeal carcinomas tissues (HC), and 26 corresponding adjacent tissues (AT). Relative microbiome profiling (RMP), and quantitative microbiome profiling (QMP) of 16S rRNA amplicon sequencing were used for analysis. Results Beta-diversity showed that abundance and phylogenetic tree in OPM group were less when compared to either HC and AT. Although HC and AT were found to have similar microbiota, Bray-Curtis based beta-diversity still highlighted differences. Fusobacterium, Porphyromonas, Haemophilus, and Peptostreptococcus at the genus level in OPM were positively correlated with HC. After categorizing HC through TNM staging, the abundance of genera Fusobacterium, Parvimonas, and Dialister were found to be enhanced in higher T classifications (T3-4) and advanced stages (Ⅳ). Conclusions QMP yielded more comprehensive results than RMP. Dysbiosis was found in OPM groups and could be used to narrow down differential microbiome for the HC group. Genera of Parvimonas, Fusobacterium, and Dialister were deemed as risk factors of advanced HPSCC.

The clinicopathological significance of PD-L1 expression assessed by the combined positive score (CPS) in head and neck squamous cell carcinoma

The expression of programmed cell death-ligand 1 (PD-L1) is being used as a predictive biomarker for immunotherapy in head and neck squamous cell carcinoma (HNSCC). Our study was a retrospective cohort that assessed PD-L1 expression levels through immunohistochemistry (IHC) in 119 surgical specimens from HNSCC patients. The expression of PD-L1 was evaluated by IHC staining using the monoclonal antibody 22C3 (Dako) and the combined positive score (CPS). The relationship between the PD-L1 expression and clinicopathologic features was analyzed. 107 cases (89.9%) and 52 cases (43.7%) were positive for PD-L1 expression when the CPS cutoff value was set at 1 and 20 respectively. The tumor stage (P = 0.022) and tumor site (P = 0.004) were significantly correlated with the PD-L1 expression (CPS ≥ 1). Non-diabetic patients (P = 0.046) were corelated to positive PD-L1 expression (CPS ≥ 20). When evaluating PD-L1 expression in 40 laryngeal squamous cell carcinomas (LSC), the nodal stage was found to be significantly associated with high expression of PD-L1 (CPS ≥ 20) (P = 0.042). As for 36 patients with hypopharyngeal squamous cell carcinomas (HPSC), the positive PD-L1 expression (CPS ≥ 1) were typically younger (P = 0.030) and patients without type II diabetes (P = 0.040). We evaluated all possible clinical prognostic factors in the univariate Cox model, and there was no significant correlation between clinical characteristics and survival. The results of our findings may help to understand the association between the PD-L1 expression and clinicopathological characteristics, and it showed no significant correlation between the expression of PD-L1 and OS in HNSCC.

Laryngeal and hypopharyngeal squamous cell carcinoma: association between quantitative parameters derived from dual-energy CT and histopathological prognostic factors.

Dual-energy computed tomography (DECT) can provide objective evaluation of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). To investigate the relationship between quantitative parameters acquired from DECT and histopathological prognostic factors in LHSCC. A total of 65 patients with LHSCC who underwent arterial phase and venous phase DECT scans were retrospectively enrolled. Iodine concentration (IC) and normalized IC (NIC) of the tumor were calculated in both the arterial (ICA and NICA) and venous (ICV and NICV) phases, and compared among different pathological grades, T stages, and lymph node stages. Receiver operating characteristic (ROC) curves were generated to evaluate their diagnostic performance. There were significantly differences on ICA and NICA among three pathological grades (ICA, P = 0.001; NICA, P = 0.002). For differentiating moderately and poorly differentiated from well-differentiated LHSCC using ICA and NICA, the areas under curve (AUCs) were 0.753 and 0.726, respectively. High T stage (T3/4) LHSCC showed significantly higher ICA (P = 0.012) and NICA (P = 0.005) than low T stage (T1/2) LHSCC. The AUCs of the ICA and NICA were 0.674 and 0.703, respectively, in discriminating high from low T stage LHSCC. Lymph node metastasis (LNM)-positive (N1/2/3) LHSCC showed significantly higher ICA (P = 0.008) and NICA (P = 0.003) than LNM-negative (N0) LHSCC. For discriminating the LNM-positive from the LNM-negative group using ICA and NICA, the AUCs were 0.697 and 0.744, respectively. ICA and NICA might be helpful in assessing histopathological prognostic factors in patients with LHSCC.

Complications and oncological outcomes after salvage surgery for recurrent and residual hypopharyngeal squamous cell carcinoma: a retrospective cohort study.

BackgroundSalvage surgery for hypopharyngeal squamous cell carcinoma (HPSCC) after radiotherapy may result in several postoperative complications and the oncological outcome is unsatisfying. Therefore, identifying the risk factors for postoperative complications and oncological outcome after salvage surgery is important. This study aimed to determine which HPSCC patients might benefit from salvage surgery following previous radiotherapy.MethodsWe retrospectively analyzed 91 HPSCC patients who underwent salvage surgery due to locoregional recurrence/residual disease after radiotherapy. The pre- and intraoperative characteristics with complications and oncological outcomes were collected through medical records and telephone follow-up. Risk factors for complications were analyzed by binary logistic regression. The oncological outcomes were assessed by overall survival (OS) after salvage surgery. Kaplan-Meier curves and Cox proportional hazard regression analysis were used for univariate and multivariate survival analyses.ResultsPostoperative complications occurred in 40.7% of patients, with pharyngo-cutaneous fistula (PCF) occurring in 29.7% of patients. Salvage surgery for local disease was the only independent risk factor for postoperative complications and PCF [complications: odds ratio (OR) =5.298, 95% confidence interval (CI): 1.163–24.130, P=0.031; PCF: OR =4.543, 95% CI: 1.187–17.387, P=0.027). In the subgroup of patients with local disease, time of curative treatment initiation >90 days (OR =7.331, 95% CI: 1.278–42.054, P=0.025) and preoperative hemoglobin <118 g/L (OR =10.101, 95% CI: 1.026–99.492, P=0.045) were independent risk factors for postoperative complications, while free flap reconstruction was an independent protective factor for PCF (OR =0.099, 95% CI: 0.010–0.934, P=0.043). The median OS time was 17 months, with 5-year OS rates of 30%. Age at salvage surgery <50 years [hazard ratio (HR) =2.047, 95% CI: 1.217–3.443, P=0.007] and recurrence or retreatment clinical T stage 3–4 (rcT3–4) (HR =2.051, 95% CI: 1.219–3.450, P=0.007) were identified as risk factors for OS. The 5-year OS rates of patients without and with both risk factors were 43% and 10% (P=0.001).ConclusionsSalvage surgery for locoregional recurrence/residual disease after previous radiotherapy could improve survival in selected patients with HPSCC. Patients with local recurrence/residual disease had a higher complication rate. Efforts can be made to shorten the time of curative treatment initiation and treat anemia to reduce the risk of postoperative complications in this subgroup.

Advanced hypopharyngeal squamous cell carcinoma mimicking thyroid abscess in a young male: Case report and literature review.

Introduction and importanceThyroid gland involvement by hypopharyngeal carcinoma is due to their close proximity. Initial presentation of such cancer as a thyroid abscess is rare in clinical practice thus risk of potential misdiagnosis. To the best of our knowledge, this is the first reported case in Tanzania.Case presentationWe present a 17-year old male who presented with difficulty in swallowing, hot potato voice, difficulty in breathing and a wound at the anterior aspect of the neck. He was managed at peripheral health facilities as having thyroid abscess so had serial incision and drainage and prescribed antibiotics. He was referred to us where he undergone tracheostomy, direct laryngoscopy coupled with taking biopsy.Clinical discussionComputerized tomography (CT scan) of the head and neck showed an ill-defined heterogeneously enhancing mass with calcifications seen at the hypopharynx extending to the larynx and thyroid gland causing destruction of cricoid cartilage. It measured approximately 7.6 × 6.5 × 4.4 cm. The submandibular and sublingual glands are slightly infiltrated. Multiple enlarged lymph nodes are seen at anterior upper jugular IIa and posterior upper jugular IIb with the largest having central necrosis and measures approximately 2.9 × 1.7 cm. Histopathology showed an ulcerated epithelium with an infiltrative tumor containing dense chromatin. Such features were consistent with invasive squamous cell carcinoma, Grade II.(TNM staging being T4bN2cM0). The patient undergone tracheostomy to relieve upper airway obstruction and sent to oncology center for chemoradiation.ConclusionClinicians should have a high index of suspicion of a possible underlying hypopharyngeal cancer whenever encountering patients with thyroid abscess.

Recurrent Carotid artery blow out in a head &amp; neck patient

Introduction and importanceCarotid artery blowout syndrome is a rare complication of head and neck cancer treatment. It defines a rupture of the carotid artery wall through vessel wall necrosis. This is typically precipitated by radiotherapy, direct tumour invasion, or a combination of these factors. We describe a rare case of three consecutive carotid artery blowouts in a head and neck cancer patient.Case presentationA 58-year-old man with a history of T3NO hypopharyngeal squamous cell carcinoma (SCC) treated with chemotherapy and radiation presented with a four-month history of progressive dysphagia and right sided neck pain. Flexible nasendoscopy revealed laryngeal oedema and slough. A panendoscopy and biopsy showed no evidence of tumour recurrence. The patient was discharged and represented with worsening dyspnoea. He subsequently experienced a large volume hemorrhage necessitating ligation of his right external carotid artery. He underwent pharyngolaryngectomy indicated due to the extent of laryngeal radiation necrosis. Thereafter he suffered two additional acute carotid bleeds from his right common carotid necessitating ligation in theatre.Clinical discussion and conclusionThis case report illustrates the key issues to be considered in patients with locally advanced hypopharyngeal squamous cell carcinoma and subsequent management of acute carotid blowout syndrome, which without prompt management, can be fatal.

MiR-211-3p enhances induction chemotherapy insensitivity by upregulating CSF2/CCL20/TNF signaling in hypopharyngeal squamous cell carcinoma.

To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC). qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration. miR-211-3p was up-regulated in IC insensitive larynx-hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis. The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration. The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy.

Clinical features and prognostic influences of retropharyngeal lymph node metastasis in oropharyngeal and hypopharyngeal squamous cell carcinoma: a meta analysis

Objective: To compare the clinical features and prognoses of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) with and without retropharyngeal lymph node metastases. Methods: PubMed, Cochrane, Web of Science, CNKI, VIP and Wanfang databases were searched for published literatures on retropharyngeal lymph node metastasis of oropharyngeal or hypopharyngeal squamous cell carcinoma (1900, 2021), and outcome indicators such as survival rate and related clinical features were extracted. The quality evaluation of the included literatures was carried out. RevMan 5.4 and Stata 16.0 software were used for data analysis. Results: A total of 18 literatures were included. Meta analysis showed that 3-year and 5-year survival rates and 5-year disease-specific survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastases were lower than those without metastases, 46.1% vs. 53.0%, 40.8% vs. 62.5% and 35.9% vs. 53.1%, respectively, and the differences were statistically significant (OR values were 0.26, 0.38, 0.38, and 95%CI were 0.10-0.69, 0.28-0.51, 0.23-0.65, respectively, all P values<0.05). There were statistically significant differences in clinical stage (III-IV), T stage (T3+T4), N stage (N2), positive cervical lymph node metastases and number of lymph node metastases (≥3) between the two groups (OR values were 4.28, 2.20, 2.88, 10.83, 6.53, and 95%CI were 1.70-10.74, 1.35-3.58, 1.90-4.34, 3.57-32.95, 1.75-24.38, respectively, all P<0.05). The sensitivity and specificity of preoperative imaging for diagnosing retropharyngeal lymph nodes metastases were respectively 0.72 (95%CI=0.54-0.85) and 0.98 (95%CI=0.74-1.00), and the area under curve (AUC) of summary receiver operating characteristic curve (SROC) was 0.84 (95%CI=0.80-0.87). Conclusions: The survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastasis is significantly reduced, the clinical stage and T stage are late, and the cervical lymph node metastasis rate is high. Retropharyngeal lymph node metastasis is more insidious, the sensitivity of preoperative imaging diagnosis is not high.

Tracheobronchial chondritis as an immune-related adverse event occurring during the administration of nivolumab for recurrent hypopharyngeal squamous cell carcinoma.

Tracheobronchial chondritis is a rare immune-related adverse event (irAE) associated with immune checkpoint inhibitors. We report a case wherein tracheobronchial chondritis occurred while administering nivolumab for recurrent hypopharyngeal squamous cell carcinoma (SCC) in a man diagnosed with T2N3bM0 stage IVB hypopharyngeal SCC. After treatment with cisplatin and radiotherapy followed by left and right neck dissection, local recurrence was observed in the hypopharynx. Because of the difficulty of salvage surgery, we administered 240mg/body of nivolumab. After 9 cycles of nivolumab, the patient was judged to have complete response. After 10 cycles, he had cough and sputum, for which prompting us to perform imaging tests. Computed tomography (CT) showed edematous thickening around the trachea and bilateral bronchi and elevated amounts of adjacent subcutaneous fat tissue. Positron emission tomography-CT showed diffuse fluorodeoxyglucose uptake in the trachea and bilateral bronchi, bronchial endoscopy showed redness and swelling throughout the bronchi, and biopsy showed partial mucosal erosion, inflammatory cell (lymphocyte) infiltration, interstitial edema, and desmoplasia. The patient was diagnosed with tracheobronchial chondritis as an irAE resulting from administering anti-programmed death-1 monoclonal antibody. After four-day prednisolone treatment, his cough and sputum disappeared; after two weeks, tracheobronchial chondritis no longer appeared on CT.

LncRNA LEF1-AS1 Acts as a Novel Biomarker and Promotes Hypopharyngeal Squamous Cell Carcinoma Progression and Metastasis by Targeting the miR-221-5p/GJA1 Axis.

Hypopharyngeal squamous cell carcinoma (HSCC) is highly malignant and extremely aggressive, making it one of the worst prognoses among all kinds of head and neck squamous cell carcinoma (HNSCC); therefore, gaining insight into molecular mechanisms of HSCC is of profound significance. In the current manuscript, we revealed the elevated expression of long noncoding RNA (lncRNA) LEF1-AS1 in HNSCC which was associated with the poor prognosis by bioinformatic analysis. Moreover, we noticed that LEF1-AS1 dramatically accelerated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in HSCC cell line FaDu. Most importantly, we illustrated that LEF1-AS1 played as a competitive endogenous RNA (ceRNA) via sponging miR-221-5p and thereby positively regulated gap junction protein alpha 1 (GJA1) expression, thus aggravated tumor progression and EMT. In conclusion, for the first time, we demonstrated lncRNA LEF1-AS1 as a novel biomarker for HNSCC and suggested LEF1-AS1/miR-221-5p/GJA1 axis as promising diagnostic and therapeutic target for HSCC treatment.

UBE2L3 promotes squamous cell carcinoma progression in the oral cavity and hypopharynx via activating the NF-κB signaling by increasing IκBα degradation.

Oral squamous cell carcinoma (OSCC) and hypopharyngeal squamous cell carcinoma (HSCC) are representative of head and neck squamous cell carcinoma (HNSCC) and the molecular pathogenesis has not been completely clarified. Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is the key member of the E2 family that encodes 153 amino acid residues. Previous studies demonstrate that UBE2L3 is aberrantly overexpressed in various types of human cancers, suggesting that UBE2L3 may function as an oncogene. However, its functional role and the potential mechanisms in the OSCC and HSCC remain unclear. In the present study, we found that UBE2L3 was significantly upregulated in clinical HNSCC samples and HNSCC cell lines, and patients with lower UBE2L3 expression have a higher survival rate. Two HNSCC cell lines FaDu (HSCC cells) and CAL-27 (OSCC cells) with moderate expression of UBE2L3 were selected for in vitro experiments. We proved that UBE2L3 overexpression was positively associated with cellular malignant phenotypes in vitro, including proliferation, invasion, migration, and tumor growth in vivo. Conversely, UBE2L3 suppression diametrically yielded opposing results. Our further study demonstrated that overexpression of UBE2L3 significantly activated the nuclear factor kappa B (NF-κB) signaling pathway through promoting NF-κB p65 nuclear translocation and the ubiquitination and degradation of IκBα protein. Additionally, UBE2L3 was proved to be targeted and negatively regulated by miR-378a-5p, and UBE2L3 overexpression reversed the effects of miR-378a-5p upregulation. Collectively, the present study indicates that UBE2L3 may promote OSCC and HSCC progression via activating the NF-κB signaling by increasing IκBα degradation, indicating that UBE2L3 may be a potential therapeutic target for the treatment of HNSCC.

Overexpression of microRNA-107 suppressed proliferation, migration, invasion, and the PI3K/Akt signaling pathway and induced apoptosis by targeting Nin one binding (NOB1) protein in a hypopharyngeal squamous cell carcinoma cell line (FaDu)

ABSTRACT Hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common head and neck cancers, with a worst prognosis owing to its aggressivity. MicroRNA-107 (miR-107) is reported to regulate the progression of various cancers. Nevertheless, its implied function in HSCC remains unclear. This study is aimed to exploring the roles and potential mechanisms of miR-107 in HSCC. We found that miR-107 expression was significantly decreased in HSCC tissues compared with the para-cancer tissues. Moreover, miR-107 overexpression by miR-107 mimics decreased FaDu cell viability, led to cell cycle arrest in G1/S phase, accelerated apoptosis, and reduced cell migration and invasion. MiR-107 possibly resulted in deactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, evidenced by the decrease of phosphorylated (p-) PI3K and p-Akt. Besides, dual-luciferase reporter assay confirmed that miR-107 might bind to the 3’UTR of Nin one binding protein 1 (NOB1), and elevated NOB1 expression in HSCC tissues and a negative correlation between miR-107 and NOB1 were found. Rescue assays demonstrated the significant roles of miR-107 in FaDu cell behavior by modulating NOB1. In addition, the tumorigenic potential of miR-107 in vivo was conducted. It was found that miR-107 overexpression in FaDu cells significantly inhibited tumor growth and led to inactivation of the PI3K/Akt signaling. The above findings revealed that miR-107 could suppress FaDu cell proliferation, migration, invasion and induced apoptosis by targeting NOB1 through the PI3K/Akt pathway, suggesting that miR-107/NOB1 axis may exert a key role in FaDu HSCC development.