Pharyngeal Squamous Cell Carcinoma Research Articles

Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study

ObjectiveTransoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. MethodsWe compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. ResultsSix hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. ConclusionPrior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Corrigendum: Tilianin extracted from Dracocephalum moldavica L. induces intrinsic apoptosis and drives inflammatory microenvironment response on pharyngeal squamous carcinoma cells via regulating TLR4 signaling pathways

Corrigendum: Tilianin extracted from Dracocephalum moldavica L. induces intrinsic apoptosis and drives inflammatory microenvironment response on pharyngeal squamous carcinoma cells via regulating TLR4 signaling pathways

Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.

The influence of tumor volume on the risk of distant metastases in head and neck squamous cell carcinomas

Background and purposeDistant metastases (DM) in head and neck squamous cell carcinomas (HNSCC) are in most circumstances non-curable. The TNM staging system is insufficient to predict the risk of DM. This study investigates if the DM risk can be predicted using a multivariate model including pre-treatment total tumor volume for both p16-positive oropharyngeal squamous cell carcinoma (OPSCC) and all other sites (other HNSCC). Materials and methodsThe study includes patients with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017 from three head and neck cancer centers. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database. Total (nodal and primary) tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems. The GTV was grouped by volume (cm3) in four intervals and included in a multivariate Cox proportional hazard regression controlled for pre-selected clinical values incl. stage. ResultsThe study includes 2,865 patients, of which 321 (11 %) had DM post-treatment. The risk of DM was assessed in a multivariate model based on 2,751 patients (p16-positive OPSCC: 1,032; and other HNSCC: 1,719). There was a significant association between GTV and the risk of DM, and in tumor volumes ≥ 50 cm3 hazard ratios of 7.6 (2.5–23.4) for p16-positive OPSCC and 4.1 (2.3–7.2) in other HNSCC were observed. ConclusionTumor volume is an independent risk factor for DM. The addition of total tumor volume to a predictive model is important to identify subgroups of HNSCC patients at high risk of DM.

Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection

Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness≥1000 μm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R= .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.

Abstract LB030: SHR-A1921, a novel TROP-2 ADC with an optimized design and well-balanced profile between efficacy and safety

Abstract Trop-2 is a promising target for ADC therapy due to its high expression in many solid tumors. The approval of Trodelvy, a Trop-2 directed ADC, for the treatment of refractory or drug-resistant triple negative breast cancer (TNBC) demonstrated the therapeutic value of Trop-2-targeted ADC. However, a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea suggests the safety of Trodelvy needs to be improved. Here, we presented a novel Trop2-directed ADC, SHR-A1921, consisting of a topoisomerase I inhibitor (Proprietary payload, SHR9265) conjugated to a proprietary IgG1 mAb via cleavable linkers. SHR-A1921 demonstrated several advantages over other Trop-2 directed ADCs in the field. SHR9265 is a novel exatecan derivative designed by Hengrui with a better liposolubility and cellular permeability. SHR-A1921 had a drug-to-antibody ratio (DAR) of 4. Compared with other Trop-2-targeted ADCs in the field, such as Trodelvy, TINA-SHR79711 (a molecule synthesized using the published structure of DS-1062), and SKB264, SHR-A1921 has considerable advantages as follows: (1) Stronger binding affinity to both human and rhesus macaque TROP-2 than TINA-SHR79711; (2) Improved plasma stability in plasma of different species presumably due to the proper steric hindrance which was purposely designed on the payload for reducing non-intended cleavage; (3) Stronger bystander cell killing effect presumably due to the increased lipophilicity of the payload vs. that of the payload in TINA-SHR79711; (4) Superior in vivo efficacy in a PSCC2 CDX Model (FaDu) with high Trop-2 expression (TGI 101% vs 53% [TINA-SHR79711] @ 1 mpk) and in an ovarian cancer CDX Model (SK-OV-3) with moderate Trop-2 expression (TGI 63% vs. 23% [TINA-SHR79711] @ 3 mpk; 87% vs. 16% [TINA-SHR79711] @ 10 mpk); (5) ≥ 2X longer half-life in patients# vs. SKB264 vs. IMMU-132, supporting more flexible dosing frequency; (6) Lower free toxin/ADC ratio# regarding PK exposure in patients compared with SKB264 (< 1% vs. 5-6%); (7) approximately linear pharmacokinetics profile in patients with T1/2 ranging from 2.5 to 4.5 days. In summary, SHR-A1921 is a novel anti-TROP2-targeted ADC with a high permeable payload and optimized DAR demonstrating great stability and high potency in both in vitro and in vivo studies. SHR-A1921 also showed compelling efficacy and good safety profile from 50+ subjects of Phase I clinical trial in China (NCT05154604). Pivotal phase III trial for NSCLC is planned in China. (Notes: 1. TINA-SHR7971 is a molecule that Hengrui synthesized using the published structure of DS-1062. 2. PSCC: pharyngeal squamous cell carcinoma. #. non-head-to-head comparison.) Citation Format: Ning He, Chunpeng Yang, Yang Yang, Zhendong Xue, Jianyan Xu, Linda Zhao, Jun Feng, Xin Ye, Zhe Zhang, Feng He. SHR-A1921, a novel TROP-2 ADC with an optimized design and well-balanced profile between efficacy and safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB030.

Cellular density and variability in laryngeal and pharyngeal squamous cell carcinoma using confocal laser endomicroscopy.

Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the cellular level of the mucosa and squamous cell carcinoma (SCC). A total of 60 CLE sequences recorded in 5 patients with SCC undergoing laryngectomy between October 2020 and February 2021 were analyzed. The corresponding histologic sample derived from H&E staining was assigned to each sequence, capturing CLE images of the tumor and healthy mucosa. In addition, the cellular structure analysis was performed to diagnose SCC by measuring the total number of cells and cell size in 60 sequences in a fixed field of view (FOV) with 240 μm in diameter (45,239 μm2). Out of 3,600 images, 1,620 (45%) showed benign mucosa and 1,980 (55%) SCC. The automated analysis yielded a difference in cell size, with healthy epithelial cells being 171.9±82.0 μm2 smaller than SCC cells, which were 246.3±171.9 μm2 and showed greater variability in size (p=0.037). In addition, due to the probe's fixed FOV, there was a difference in cell count with a total of 188.7±38.3 and 124.8±38.6 cells in images of normal epithelium and SCC (p<0.001), respectively. Regarding cell density as a criterion for the differentiation of benign/malign, using a cut-off value of 145.5 cells/FOV, we obtained sensitivity and specificity of 88.0% and 71.9%, respectively. SCC reveals marked differences at a cellular level compared to the healthy epithelium. Our results further support the importance of this feature for identifying SCC during CLE imaging.

The value of serum p53 antibody as a biomarker in oral and pharyngeal squamous cell carcinoma

Background The development of more sensitive biomarkers for the detection of early-stage head and neck squamous cell carcinoma is needed. Aims/Objectives This study was performed to assess the value of serum p53 antibody (s-p53-Ab) as a biomarker for oral and pharyngeal carcinoma. Material and Methods Pre-treatment serum was collected for 71 patients with oral and pharyngeal carcinoma and 117 healthy volunteers as controls and analyzed s-p53-Ab using enzyme-linked immunosorbent assay (ELISA). Results Using 1.3 U/mL as the cut-off value, 14 of 71 patients (sensitivity 19.7%), and 12 of 117 control cases were positive for s-p53-Ab (specificity 89.7%). Excluding 12 cases of p16-positive oropharyngeal and nasopharyngeal cancer which were all negative for s-p53-Ab, the sensitivity in early-stage 1–2 cases was 30.0%, which was higher than conventional tumor markers. Conclusions and Significance The s-p53-Ab was not detected in any cases of virus-related cancer in which p53 gene mutations were not involved in carcinogenesis. Since the s-p53-Ab sensitivity was high even in early-stage disease, s-p53-Ab measurement may be useful as an early diagnostic biomarker in patients with oral, p16- oropharyngeal, and hypopharyngeal cancer.

Human Papilloma Virus-Associated Oral Pharyngeal Squamous Cell Carcinoma: Prevalence, Prevention, and Awareness of Vaccination in the Indian Population.

Human papilloma virus (HPV), one of the most common sexually transmitted infections, plays a pivotal role in head and neck cancer, primarily oral and oropharyngeal squamous cell carcinomas. HPV is a vaccine-preventable disease that also contributes to cervical cancer. Although HPV vaccination effectively protects the individual against all HPV-associated human carcinomas, the awareness of HPV vaccination and its acceptance is poor in developing nations like India. India has a very high burden of oral cancer, and, unfortunately, the morbidity and mortality rates are also high as the cancer is often detected at an advanced stage. In this review, we explore the prevalence of HPV-associated head and neck squamous cell carcinoma among the Indian population and the awareness of HPV vaccination among Indian youth. Since the prognosis for HPV-associated head and neck squamous cell carcinoma is good, early diagnosis of the cancer is crucial in improving the outcome of the treatment modalities. Efforts are needed to create and increase awareness of HPV vaccination. Routine screening for HPV infection in oral mucosa can prevent the silent epidemic from taking the lives of many young people.

Effects of cimifugin on cell growth inhibition and cell apoptosis induction in fadu human pharyngeal squamous cell carcinoma

Effects of cimifugin on cell growth inhibition and cell apoptosis induction in fadu human pharyngeal squamous cell carcinoma

Targeting EIF3C to suppress the development and progression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.

Conventional imaging is useful for assessment of equine pharyngeal squamous cell carcinoma but underestimates bone involvement

SummaryBackgroundSquamous cell carcinoma is the most common pharyngeal neoplasm but is poorly documented with diagnostic imaging in veterinary literature.ObjectivesTo describe the diagnostic imaging findings in horses with confirmed pharyngeal squamous cell carcinoma.Study designRetrospective case series.MethodsHorses with a definitive diagnosis of pharyngeal squamous cell carcinoma based on in situ biopsy and/or cytology were identified in 2 different centres. Multi‐modality imaging findings are reported.ResultsSix equids were included. On radiographic examination, increased pharyngeal opacity and reduction of pharyngeal lumen were observed in all horses, centred on the oropharynx (three cases), the laryngopharynx (two cases) or the nasopharynx (one case). A clearly delineated mass was visualised in four cases. Additional radiographic findings were border effacement of the epiglottis (5/6) or soft palate (3/6), thickening of the pharyngeal walls (4/6) or soft palate (3/6) and suspected retropharyngeal lymphadenomegaly (3/6). Ultrasonography was useful to highlight retropharyngeal (4/6) and mandibular (4/6) lymphadenopathy suggestive of metastatic dissemination. Computed tomographic images were available for two horses and detected bone lysis not visible on radiographs.Main limitationsThe number of cases was low, and computed tomography was not realised in all cases.ConclusionsFindings support the usefulness of radiography and ultrasonography in horses with suspected pharyngeal neoplasia for a first‐line imaging diagnosis, in particular when endoscopy is impaired by a mass effect or dyspnoea. Computed tomography gives a more accurate assessment of bone involvement.

Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification.

Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects.

Abstract 2400: Fucosyltransferase expression is associated with head and neck cancer survival

Abstract Introduction: Head and neck (H&amp;N) cancers account for 5-7% of new cancer cases in the United States, and most manifest as head and neck squamous cell carcinomas (HNSCC). Fucosyltransferases (FUTs) contribute to the formation of sialofucosylated epitopes, which alter cellular signaling and mediate early steps in metastasis. However, few studies have examined the effect of FUT expression on H&amp;N cancer survival. Here, we sought to examine the association between fucosyltransferase expression and H&amp;N survival and investigate the mechanistic role of fucosylation in H&amp;N cancer. Methods: FUT1-11 expression (mRNA) data was extracted from the Cancer Genome Atlas (TCGA) HNSCC dataset (n=499). Kaplan-Meier, logrank, and Cox proportional hazards tests were conducted. Levels of α1,2-fucosylated epitopes H-antigen, Lewis Y (LeY), and Lewis B (LeB) were measured in normal, dysplastic, and H&amp;N tumor cell lines via flow cytometry, and RT-qPCR was performed to assess FUT expression. To identify fucosylated signaling and adhesion molecules, fucosylated glycopeptides were enriched from CAL27 and HSC-3 tongue squamous cell carcinoma (SCC) lysates via AAL lectin, followed by nLC-MS/MS. EGFR signaling was assessed via western blot, and parallel plate flow assays were performed to assess in vitro metastatic potential, in tumor cell lines with differential FUT expression. Results: In TCGA analyses, the median survival time (MST) of the FUT2 high expression group was 4.7 years, while low expression group MST was 2.7 years, with an adjusted hazard ratio (aHR) of 0.72 (CI = 0.54-0.95). The FUT6-high group MST was 4.7 years versus 2.9 years for low expression (aHR = 0.62, CI = 0.47-0.83). The FUT7-high group MST was 4.7 years versus 3.5 years for low expression (aHR = 0.72, CI = 0.54-0.95). Expression of the LeY epitope, with both α1,2- and α1,3-linked fucose, varied widely in tongue SCC lines, while pharyngeal SCC lines FaDu and Det-562 displayed intermediate LeY levels, via flow cytometry. EGFR, CD44, and integrins, were among the fucosylated glycoproteins identified via mass spectrometry. HSC-3 cells, sorted into low- and high-LeY populations, demonstrated differential EGFR Tyr-1086 phosphorylation, and differences in adhesion to endothelial cells under flow conditions (in vitro), with implications for tumor metastasis. Conclusion: Overexpression of FUT2, FUT6, and FUT7 were associated with statistically significant increases in survivorship. FUT6 and FUT7 are prominently expressed in immune cells, while FUT2 is expressed in endoderm-derived epithelium. Therefore, FUT6 and FUT7 expression may indicate immune cell infiltration into tumor tissue. Future studies will seek to sort tumor tissue based on cell type, to gain an understanding of the cell-type specific glycosyltransferase expression in HNSCC tumors. Our current results will serve as the foundation to interrogate the role of fucosylated glycoproteins in HNSCC metastasis. Citation Format: Kevin Brown Chandler, Brittany Montesino, Nan Hu, Juan M. Lozano, Robert Sackstein. Fucosyltransferase expression is associated with head and neck cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2400.

Discovery of a potent cytotoxic agent that promotes G2/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line.

Squamous cell carcinoma is the major form of malignancy that arises in head and neck cancer. The modest improvement in the 5‑year survival rate underpins its complex etiology and provides the impetus for the discovery of new therapeutics. The present study describes the discovery of an indole‑based small molecule(24a) that was a potent cytotoxic agent with antiproliferative and pro‑apoptotic properties against a pharyngeal carcinoma cell line, Detroit562, effectively killing the cells at a half‑maximal inhibitory concentration of 0.03µM, as demonstrated using cell proliferation studies. The antiproliferative property of 24a was demonstrated by its ability to promote G2/M blockade, as assessed by cell cycle analysis using flow cytometry and the monitoring of real‑time cell cycle progression by the fluorescence ubiquitination‑based cell cycle indicator. This pro‑apoptotic property is supported by the promotion of TUNEL‑staining and increase in the activities of caspases‑3/7 and ‑6, in addition to the expression of death receptors and the cleavage of poly (ADP‑ribose) polymerase1 protein as demonstrated by western blotting. Given that Detroit562 lacks functional p53, it is suggested that 24a acts independently of the tumor suppressor.

MiR-1269a and miR-1269b: Emerging Carcinogenic Genes of the miR-1269 Family

miRNAs play an important role in the occurrence and development of human cancer. Among them, hsa-mir-1269a and hsa-mir-1269b are located on human chromosomes 4 and 17, respectively, and their mature miRNAs (miR-1269a and miR-1269b) have the same sequence. miR-1269a is overexpressed in 9 cancers. The high expression of miR-1269a not only has diagnostic significance in hepatocellular carcinoma and non-small cell lung cancer but also is related to the poor prognosis of cancer patients such as esophageal cancer, hepatocellular carcinoma, and glioma. miR-1269a can target 8 downstream genes (CXCL9, SOX6, FOXO1, ATRX, RASSF9, SMAD7, HOXD10, and VASH1). The expression of miR-1269a is regulated by three non-coding RNAs (RP11-1094M14.8, LINC00261, and circASS1). miR-1269a participates in the regulation of the TGF-β signaling pathway, PI3K/AKT signaling pathway, p53 signaling pathway, and caspase-9-mediated apoptotic pathway, thereby affecting the occurrence and development of cancer. There are fewer studies on miR-1269b compared to miR-1269a. miR-1269b is highly expressed in hepatocellular carcinoma, non-small cell lung cancer, oral squamous cell carcinoma, and pharyngeal squamous cell carcinoma, but miR-1269b is low expressed in gastric cancer. miR-1269b can target downstream genes (METTL3, CDC40, SVEP1, and PTEN) and regulate the PI3K/AKT signaling pathway. In addition, sequence mutations on miR-1269a and miR-1269b can affect their regulation of cancer. The current studies have shown that miR-1269a and miR-1269b have the potential to be diagnostic and prognostic markers for cancer. Future research on miR-1269a and miR-1269b can focus on elucidating more of their upstream and downstream genes and exploring the clinical application value of miR-1269a and miR-1269b.At present, there is no systematic summary of the research on miR-1269a and miR-1269b. This paper aims to comprehensively analyze the abnormal expression, diagnostic and prognostic value, and molecular regulatory pathways of miR-1269a and miR-1269b in multiple cancers. The overview in our work can provide useful clues and directions for future related research.

Comprehensive risk evaluation for metachronous carcinogenesis after endoscopic submucosal dissection of superficial pharyngeal squamous cell carcinoma.

Pharyngeal squamous cell carcinoma (PSCC) is associated with a high likelihood of metachronous carcinogenesis, which is known to have a poor prognosis. This study aimed to identify comprehensive risk evaluation indicators for metachronous carcinogenesis after endoscopic submucosal dissection (ESD) of superficial PSCC. The risk of metachronous carcinogenesis was evaluated in 144 patients with superficial PSCC (with no history of PSCC or esophageal squamous cell carcinoma) who underwent initial ESD from 2008 to 2020. Multiple lugol-voiding lesions (LVLs) in the background pharyngeal and esophageal epithelium were evaluated as endoscopic indicators. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score was analyzed as a serum marker. The median follow-up period was 4.3years. The coincidence rate for pharyngeal and esophageal LVL grade was 55%. The cumulative 3-year metachronous PSCC rate was 18.9%. The cumulative 3-year second metachronous PSCC rate was 43.9%. Forward stepwise multivariate Cox proportional hazards regression analysis identified pharyngeal LVL grade and a lower HALP score as significant independent predictors. Pharyngeal LVL grade was superior to esophageal LVL grade as a predictor of metachronous PSCC. A lower HALP score was significantly associated with younger age in forward stepwise multivariate logistic regression analysis. Patients with a history of superficial PSCC remain at risk for metachronous carcinogenesis over time, and long-term follow-up is imperative. Comprehensive evaluation of endoscopic features with a novel serum marker, namely, the HALP score, can help predict metachronous carcinogenesis.

Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUNDIn recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC).AIMTo clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy.METHODSThis is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann–Whitney U test. Pearson’s χ2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan–Meier method was used to estimate the cumulative patient survival rates.RESULTSIn our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE (P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE (P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively.CONCLUSIONGastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.