Stage Squamous Cell Carcinoma Research Articles

Determinants of Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma With Nodal Metastases

The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE). To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease. This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients. Curative intent surgery ± adjuvant radiotherapy. Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis. Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors. The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.

SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment.

Despite significant advancements in the field of oncology, cancers still pose one of the greatest challenges of modern healthcare. Given the cytoskeleton's pivotal role in regulating mechanisms critical to cancer development, further studies of the cytoskeletal elements could yield new practical applications. Septins represent a group of relatively well-conserved GTP-binding proteins that constitute the fourth component of the cytoskeleton. Septin 9 (SEPT9) has been linked to a diverse spectrum of malignancies and appears to be the most notable septin member in that category. SEPT9 constitutes a biomarker of colorectal cancer (CRC) and has been positively correlated with a high clinical stage in breast cancer, cervical cancer, and head and neck squamous cell carcinoma. SEPT9_i1 represents the most extensively studied isoform of SEPT9, which substantially contributes to carcinogenesis, metastasis, and treatment resistance. Nevertheless, the mechanistic basis of SEPT9_i1 oncogenicity remains to be fully elucidated. In this review, we highlight SEPT9's and SEPT9_i1's structures and interactions with Hypoxia Inducible Factor α (HIF-1 α) and C-Jun N-Terminal Kinase (JNK), as well as discuss SEPT9_i1's contribution to aneuploidy, cell invasiveness, and taxane resistance-key phenomena in the progression of malignancies. Finally, we emphasize forchlorfenuron and other septin inhibitors as potential chemotherapeutics and migrastatics.

Hematological Parameters at Baseline: A Novel Prognostic Factor for Cervical Cancer Patients Undergoing Concurrent Chemoradiotherapy in South India.

Introduction In cervical cancer treatment, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-globulin ratio (AGR) are being studied as potential prognostic markers for predicting the effectiveness of concurrent chemoradiotherapy (CCRT). This study aims to investigate the relationship between these biomarkers and survival outcomes in cervical cancer patients undergoing CCRT. Materials and methods This retrospective study was conducted at Amrita Institute of Medical Sciences between January 2016 and December 2019. It included patients at any stage who received definitive CCRT and were followed for at least two years post-treatment. Patients who had initial surgery and those lost to follow-up were excluded. Results The study included 123 patients with a median age of 68. Most patients had stage IIB (39%) and squamous cell carcinoma (76.4%). With a median follow-up of 56 months, the five-yearoverall survival (OS) was 66.8%, progression-free survival (PFS) was 94%, and recurrence-free survival (RFS) was 81.2%.AGR (p = 0.001), NLR (p = 0.0001), and PLR (p = 0.001) were found to be significantly associated with OS, NLR (p = 0.002) and AGR (p = 0.001) significantly affected RFS, while only PLR (p = 0.02) significantly affected PFSon univariate analysis. NLRsignificantly impacted OS (p = 0.003) and RFS(p = 0.03) on multivariate analysis. Conclusion The results of our study showed that increased NLR and elevated levels of albumin indicate a higher likelihood of mortality. Furthermore, a higher NLR was linked to an increased probability of recurrence in patients with cervical cancer who received primary treatment with CCRT. Therefore, the identification of predictive biomarkers could significantly improve the assessment of progression risk, aiding in the selection of the most suitable treatment and personalized therapy.

Preoperative thromboelastography parameters in predicting the tumour stage of oral squamous cell carcinoma

BackgroundA variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis.MethodsData on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed.ResultsHypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage.ConclusionsPreoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.

FAM83D promotes the progression of 4NQO-induced esophageal carcinoma via inhibiting FBWX7

The present study aimed to explore the expression and regulatory role of FAM83D in the different developmental stages of esophageal squamous cell carcinoma (ESCC) to determine the effect of FAM83D on the proliferation, migration, and invasion of ESCC cells and to elucidate its underlying molecular mechanism. Immunohistochemistry (IHC) analysis revealed that the expression of FAM83D was obviously elevated in ESCC tissues compared to adjacent normal tissues. Furthermore, the FAM83D levels was positively correlated with tumor size, TNM stage, T stage, and N stage, while it was negatively correlated with FBXW7 expression, Karnofsky Performance Status (KPS) score, and survival rate. Subsequently, ESCC cell lines with low FAM83D expression were constructed using RNA interference technology to investigate the impact of FAM83D on the biological behavior of ESCC cells. Silencing of FAM83D inhibited the proliferation and migration of ESCC cells but promoted apoptosis. Furthermore, a reduction in FAM83D expression may also induce cell cycle arrest at the G0/G1 phase and regulate the expression of proteins related to epithelial-mesenchymal transition (EMT), the cell cycle, and apoptosis. Further research indicated that silencing FAM83D led to the upregulation of FBXW7 expression. These results suggested that FAM83D may exert its effects on ESCC by downregulating FBXW7. Additionally, using a 4NQO solution in the drinking water to establish an ESCC mouse model, IHC analysis revealed that FAM83D expression levels were positively correlated with the pathological grade of esophageal lesions in the mice and negatively correlated with the expression levels of FBXW7 and E-cadherin. The above results demonstrated that FAM83D may facilitate the progression of ESCC by negatively regulating FBXW7 expression and that FAM83D could represent a promising therapeutic target for ESCC.

780. NEOADJUVANT IMMUNOTHERAPY COMBINED WITH CHEMORADIOTHERAPY VS NEOADJUVANT CHEMORADIOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL CARCINOMA (CSTAGEII-III): A MULTI-CENTER PROSPECTIVE RANDOMIZED CLINICAL TRIAL (ICROSS)

Abstract Background The role of neoadjuvant immunotherapy combined with chemoradiation in the treatment of esophageal cancer is not yet fully understood. This study aims to compare the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiation versus traditional neoadjuvant chemoradiation in treating locally advanced esophageal squamous cell carcinoma (stages cII-III). Methods This prospective randomized controlled trial included histologically confirmed patients with potentially resectable esophageal squamous cell carcinoma (stages cII-cIII). Patients were randomly assigned to two groups: the treatment group (Arm A) received BGB-A317 (200mg IV) combined with the CROSS regimen of chemotherapy and radiation, while the control group (Arm B) received only the CROSS chemotherapy and radiation regimen. All patients underwent surgery followed by a five-year follow-up. The primary endpoints included pathological complete response rate (pCR), tumor regression grades, and lymph node clearance. Results The study enrolled 67 patients (52 males, 15 females) aged between 18-75 years. Tumor locations were as follows: upper segment in 16 cases, middle segment in 45 cases, and lower segment in 6 cases. A total of 64 patients were included in the analysis. There were no significant differences between the two groups in terms of pCR rates (Arm A 41.4% vs. Arm B 30.8%, p=0.414), tumor regression grades, Surgical time (221.09 ± 37.54 minutes vs. 227.05 ± 50.28 minutes, p=0.593), Estimated blood loss (182.73 ± 337.41 ml vs. 90.47 ± 66.36 ml, p=0.109), and postoperative hospital stay (9.31 ± 4.12 days vs. 8.42 ± 1.16 days, p=0.555). However, the treatment group had significantly more lymph nodes retrieved during surgery compared to the control group (26.86 ± 7.96 vs. 20.85 ± 9.68, p=0.020). The safety profiles were similar between the groups with no significant adverse events observed. Conclusion For patients with locally advanced esophageal squamous cell carcinoma, neoadjuvant immunotherapy combined with chemoradiation is comparable in efficacy and safety to neoadjuvant chemoradiation alone and may facilitate more effective lymph node clearance. Although these preliminary results are encouraging, further long-term follow-up and larger-scale studies are needed to validate these clinical findings once the study is complete.

Inspection of Deep Tumor Margins for Accurate Cutaneous Squamous Cell Carcinoma Staging.

Inspection of Deep Tumor Margins for Accurate Cutaneous Squamous Cell Carcinoma Staging.

Intravoxel incoherent motion diffusion-weighted imaging in evaluating preoperative staging of esophageal squamous cell carcinoma

BackgroundThe aim of this research is to prospectively investigate the diagnostic performance of intravoxel incoherent motion (IVIM) using the integrated slice-specific dynamic shimming (iShim) technique in staging primary esophageal squamous cell carcinoma (ESCC) and predicting presence of lymph node metastases from ESCC.MethodsSixty-three patients with ESCC were prospectively enrolled from April 2016 to April 2019. MR and IVIM using iShim technique (b = 0, 25, 50, 75, 100, 200, 400, 600, 800 s/mm2) were performed on 3.0T MRI system before operation. Primary tumour apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f) were measured by two independent radiologists. The differences in D, D*, f and ADC values of different T and N stages were assessed. Intraclass correlation coefficients (ICCs) were calculated to evaluate the interobserver agreement between two readers. The diagnostic performances of D, D*, f and ADC values in primary tumour staging and prediction of lymph node metastasis of ESCC were determined using receiver operating characteristic (ROC) curve analysis.ResultsThe inter-observer consensus was excellent for IVIM parameters and ADC (D: ICC = 0.922; D*: ICC = 0.892; f: ICC = 0.948; ADC: ICC = 0.958). The ADC, D, D* and f values of group T1 + T2 were significantly higher than those of group T3 + T4a [ADC: (2.55 ± 0.43) ×10− 3 mm2/s vs. (2.27 ± 0.40) ×10− 3 mm2/s, t = 2.670, P = 0.010; D: (1.82 ± 0.39) ×10− 3 mm2/s vs. (1.53 ± 0.33) ×10− 3 mm2/s, t = 3.189, P = 0.002; D*: 46.45 (30.30,55.53) ×10− 3 mm2/s vs. 32.30 (18.60,40.95) ×10− 3 mm2/s, z=-2.408, P = 0.016; f: 0.45 ± 0.12 vs. 0.37 ± 0.12, t = 2.538, P = 0.014]. The ADC, D and f values of the lymph nodes-positive (N+) group were significantly lower than those of lymph nodes-negative (N0) group [ADC: (2.10 ± 0.33) ×10− 3 mm2/s vs. (2.55 ± 0.40) ×10− 3 mm2/s, t=-4.564, P < 0.001; D: (1.44 ± 0.30) ×10− 3 mm2/s vs. (1.78 ± 0.37) ×10− 3 mm2/s, t=-3.726, P < 0.001; f: 0.32 ± 0.10 vs. 0.45 ± 0.11, t=-4.524, P < 0.001]. The combination of D, D* and f yielded the highest area under the curve (AUC) (0.814) in distinguishing group T1 + T2 from group T3 + T4a. D combined with f provided the highest diagnostic performance (AUC = 0.849) in identifying group N + and group N0 of ESCC.ConclusionsIVIM may be used as an effective functional imaging technique to evaluate preoperative stage of primary tumour and predict presence of lymph node metastases from ESCC.

The analysis on Tiam2 for expression in esophageal carcinoma: A descriptive study.

To investigate T lymphoma invasion and metastasis inducing factor 2 (Tiam2) protein for expression in esophageal carcinoma and relationship with clinical features among cases with tumors. In primary esophageal cancer patients, surgical resection of tumor tissue was performed in 65 cases and adjacent normal esophageal tissue in 20 cases. Primary esophageal carcinoma (57 cases squamous cell carcinoma, 8 cases adenosquamous carcinoma). The expression level of Tiam2 protein in esophageal carcinoma tissues and normal esophageal tissues by SP immunohistochemical method. The expression intensity was quantitatively analyzed by using Image-pro plus software for image analysis, while SPSS26.0 software was used for a statistical analysis on the data. Tiam2 was highly expressed in esophageal squamous cell carcinoma and adenosquamous cell carcinoma, but low expressed in normal esophageal tissue. The expression level of Tiam2 protein was not correlated with gender and age of patients (P > .05), but was correlated with lymph node metastasis of esophageal carcinoma, TNM stage and differentiation degree of esophageal squamous cell carcinoma (P < .05). Tiam2 was positively correlated with Tiam1 for protein expression in esophageal carcinoma (r = .704, P < .001). The increased expression of Tiam2 protein in esophageal cancer may be an early molecular event of esophageal cancer. Tiam2 protein has a high expression level in esophageal carcinoma related to lymph node metastasis, TNM stage and differentiation degree, which suggests that Tiam2 protein plays an important role in the invasion and metastasis of esophageal carcinoma. There is a positive correlation between Tiam2 and Tiam1 protein expressions in esophageal carcinoma, suggesting that the 2 proteins may have a definite internal relationship.

Postoperative Radiotherapy in Advanced Stage Squamous Cell Carcinoma Requiring Maxillectomy.

To evaluate whether postoperative radiotherapy (PORT) improves survival among patients who received maxillectomy for pT4aN0 maxillary gingival or hard palate squamous cell carcinoma (SCC) with respect to tumor size. Retrospective analysis. National Cancer Database from 2004 to 2019. Included adult patients who received maxillectomy (partial, subtotal, or total) and neck dissection for treatment-naive margin negative pT4aN0 SCC of the maxillary gingiva or hard palate. Adjusted for age, gender, race, insurance status, income, education, urban/rural, facility type, region, comorbidity index, tumor grade, and tumor extension. Inverse probability weights were incorporated into a multivariable Cox proportional hazards model. A priori post hoc subgroup analysis was performed according to tumor size. We included 416 patients who underwent maxillectomy for pT4aN0 SCC of the maxillary gingiva or hard palate (mean [standard deviation] age, 71.5 [11.3] years; male, 190 [45.7%]; tumor size 2 cm, 362 [87%]). Overall, 49.3% of patients received PORT (205 patients). PORT was associated with a 50% improvement in survival compared to surgery alone (adjusted hazard ratio [aHR], 0.50; 95% confidence interval [95% CI], 0.32-0.81). On subgroup analysis, PORT was associated with improved survival for tumors 2 cm (aHR, 0.47; 95% CI, 0.29-0.77), but not for tumors < 2 cm (aHR, 1.15; 95% CI, 0.33-4.08). The vast majority of patients with pT4aN0 bone-invading SCC of the maxillary gingiva and hard palate benefit from PORT. Patients with tumors < 2 cm did not demonstrate a survival benefit from adjuvant treatment, suggesting that bony invasion alone may not be sufficient criteria for treatment escalation.

Next-generation sequencing as a valuable tool for mutational spectrum in advanced-stage NSCLC patients.

Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer. Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection. To analyze the mutational landscape of these patients, we employed plasma DNA for the next-generation sequencing (NGS) cancer panel Ion Torrent, which contains 50 of the most mutated genes in lung cancer. All protocols for extraction, quality and quantity control, and library preparation follow the manufacturer's rules. Bioinformatics analysis was performed to select pathogenic mutations versus non-pathogenic-benign ones. This approach is particularly valuable for patients in advanced stages (III and IV, n=10) of lung adenocarcinoma and lung squamous cell carcinoma, who lack surgical options and limited therapeutic avenues. The comprehensive sequencing analysis revealed that nine of the ten lung cancer patients carried a TP53 mutation. Also, several other mutations exist in various cases, showing heterogeneous profiling. Our findings demonstrate the potential of liquid biopsies in providing crucial genetic insights that can guide personalized treatment strategies, improving the management and outcomes for patients with advanced lung cancer.

Immune checkpoint inhibitor use in head and neck squamous cell carcinoma: the current landscape and future perspectives.

Immune checkpoint inhibitors are licensed for use in patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma. Multiple published and ongoing trials are assessing efficacy in the curative management of patients in the concomitant, neoadjuvant and/or adjuvant settings, as well as part of multimodality treatment in patients with metastatic disease. This review evaluates the evidence for use of immune checkpoint inhibitors in all stages of head and neck squamous cell carcinoma and considers future approaches.

Neck dissection of cN0 maxillary oral squamous cell carcinoma: A study based on SEER database

ObjectiveFor patients with clinical nodal-negative (cN0) maxillary oral squamous cell carcinoma (MOSCC), neck dissection (ND) and clinical observation are the main two management strategies for the neck. However, the indications corresponding to these two options remain controversial. This study aimed to elucidate the clinical factors affecting ND treatment and to identify clinical characteristics of the population that may benefit from ND based on a retrospective analysis of cN0 MOSCC patient data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods8846 MOSCC patients were identified in the SEER database from 2000 to 2020. The Kaplan-Meier method was utilized to examine overall survival (OS) and disease-specific survival (DSS), while the hazard ratio (HR) was estimated using the stepwise multivariate Cox regression model. Furthermore, multi-subgroup analyses of DSS and OS were performed to compare ND and No ND. ResultsWe included 2,512 cN0 MOSCC patients. Basic survival analysis and Cox regression modeling showed that ND was an independent prognostic factor that promoted DSS and OS. Additional subgroup analyses revealed that the primary site and T-stage might influence the efficacy of ND modality. Moreover, patients with T3/T4 stage of upper gingival squamous cell carcinoma (UGSCC) (DSS p = 0.009, OS p = 0.004), hard palate squamous cell carcinoma (HPSCC) (DSS p = 0.001, OS p < 0.001), and soft palate squamous cell carcinoma (SPSCC) (p = 0.029) showed a better survival benefit with ND in OS and DSS. Nonetheless, no differences were observed in OS and DSS between ND and No ND at the T1/T2 stage of the abovementioned primary tumor sites. Additionally, the DSS outcomes for T1/T2 stage upper lip squamous cell carcinoma (ULSCC) patients were significantly worse in the ND group than in the No ND group (p = 0.018). However, no significant differences were noted in OS (p = 0.140) as well as OS (p = 0.248) and DSS (p = 0.627) for T1/T2 and T3/T4 patients, respectively. ConclusionActive surveillance might be a feasible strategy for managing all T-staged ULSCC as well as early-stage (T1/T2) UGSCC, SPSCC, and HPSCC, provided regular and meticulous follow-up is performed. Hence, concurrent ND is recommended for patients with intermediate to advanced (T3/T4) stage UGSCC, SPSCC, and HPSCC.

A Concordance Between Clinical and Pathological Tumor Staging of Oral Squamous Cell Carcinoma: An Institutional Study.

Among oral diseases, oral cancer is the primary cause of death and poses a serious health risk. Primary tumor (T) - regional lymph node (N) - distant metastasis (M) comprising (TNM) staging is crucial for planning treatment strategies for patients with oral squamous cell carcinoma (OSCC). This study evaluated the predictive accuracy of clinical TNM staging of OSCC to histopathological staging (pTNM) in an institutional setting. Fifty-four consecutive histologically confirmed, surgically treated OSCC cases were evaluated for TNM staging. The study compared the clinical staging at the time of surgery with the pathological staging obtained from excisional biopsy reports. Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) was used for the data compilation and descriptive analysis. The chi-square test, analysis of variance (ANOVA), and Tukey's Honest Significant Difference (HSD) posthoc test were used to compare the data for statistical significance with p value <0.05 using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). The alveolar mucosa (n=22, 40.74%) was the most frequently occurring site, followed by the tongue (n=17, 31.48%). Out of the 54 included cases, based on clinical tumor size, there were T1 (n=6), T2 (n=13), T3 (n=13), T4a (n=16) and T4b (n=6). T2 tumors were usually upstaged (n=7) while T4a (n=8) tumors were most often downstaged. T4a (n=8) had the best concordance between clinical and histopathological staging, followed by T2, T3, and T1. In nodal status, N1 showed the most variation. The chi-squared test showed statistical significance for tumor size comparison (p <0.001) and nodal status comparison (p=0.002). ANOVA test did not show any statistical significance. Tukey's HSD posthoc test showed statistical significance (p=0.034) for N0 and N1 status. The highest concordance was shown by N0 and N1 followed by N2b. Preoperative radiological and clinical assessments are essential for deciding on a patient's course of treatment. However, not all patients may require radiographs to determine tumor size or nodal status assessment. Accurate diagnosis is vital for the treatment planning of OSCC.

Jag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool

Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.

Insights into metastatic roadmap of head and neck cancer squamous cell carcinoma based on clinical, histopathological and molecular profiles.

The incidence of head and neck cancer (HNC), constituting approximately one in ten cancer cases worldwide, affects approximately 644,000 individuals annually. Managing this complex disease involves various treatment modalities such as systemic therapy, radiation, and surgery, particularly for patients with locally advanced disease. HNC treatment necessitates a multidisciplinary approach due to alterations in patients' genomes affecting their functionality. Predominantly, squamous cell carcinomas (SCCs), the majority of HNCs, arise from the upper aerodigestive tract epithelium. The epidemiology, staging, diagnosis, and management techniques of head and neck squamous cell carcinoma (HNSCC), encompassing clinical, image-based, histopathological and molecular profiling, have been extensively reviewed. Lymph node metastasis (LNM) is a well-known predictive factor for HNSCC that initiates metastasis and significantly impacts HNSCC prognosis. Distant metastasis (DM) in HNSCC has been correlated to aberrant expression of cancer cell-derived cytokines and growth factors triggering abnormal activation of several signaling pathways that boost cancer cell aggressiveness. Recent advances in genetic profiling, understanding tumor microenvironment, oligometastatic disease, and immunotherapy have revolutionized treatment strategies and disease control. Future research may leverage genomics and proteomics to identify biomarkers aiding individualized HNSCC treatment. Understanding the molecular basis, genetic landscape, atypical signaling pathways, and tumor microenvironment have enhanced the comprehension of HNSCC molecular etiology. This critical review sheds light on regional and distant metastases in HNSCC, presenting major clinical and laboratory features, predictive biomarkers, and available therapeutic approaches.

Differences in postoperative prognosis between early-stage lung adenocarcinoma and squamous cell carcinoma.

Although prognosis and treatments differ between small-cell- and nonsmall-cell carcinoma, comparisons of the histological types of NSCLC are uncommon. Thus, we investigated the oncological factors associated with the prognosis of early-stage adenocarcinoma and squamous cell carcinoma. We retrospectively compared the clinicopathological backgrounds and postoperative outcomes of patients diagnosed with pathological stage I-IIA adenocarcinoma and squamous cell carcinoma primary lung cancer completely resected at our department from January 2007 to December 2017. Multivariable Cox regression analysis for overall survival and recurrence-free survival was performed. The median follow-up duration was 55.2months. The cohort consisted of 532 adenocarcinoma and 96 squamous cell carcinoma patients. A significant difference in survival was observed between the two groups, with a 5-year overall survival rate of 90% (95% confidence interval 86-92%) for adenocarcinoma and 77% (95% CI 66-85%) for squamous cell carcinoma (P<0.01) patients. Squamous cell carcinoma patients had worse outcomes compared to adenocarcinoma patients in stage IA disease, but there were no significant differences between the two groups in stage IB or IIA disease. In multivariate analysis, invasion diameter was associated with overall survival in adenocarcinoma (hazard ratio 1.76, 95% confidence interval 1.36-2.28), but there was no such association in squamous cell carcinoma (hazard ratio 0.73, 95% confidence interval 0.45-1.14). The importance of tumor invasion diameter in postoperative outcomes was different between adenocarcinoma and squamous cell carcinoma. Thus, it is important to consider that nonsmall-cell carcinoma may have different prognoses depending on the histological type, even for the same stage.

Stratified Prognostic Comparison Between Stage IIB-IVA Cervical Adenocarcinoma and Squamous Cell Carcinoma: A SEER Database-Based Study.

In current most observational studies, the prognosis of cervical adenocarcinoma is worse than that of cervical squamous cell carcinoma. However, most of the current studies are holistic and lack more detailed staging and grouping analysis of the prognosis of the two types of cervical tumors. Inclusion from the SEER database of stage IIB-IVA cervical squamous cell carcinoma and cervical adenocarcinoma patients who did not undergo surgery from 2000 to 2019, underwent radiotherapy/chemotherapy/radiotherapy and chemotherapy/no treatment, and then propensity score matching (PSM) was performed to eliminate confounding factors between cervical squamous cell carcinoma and cervical adenocarcinoma patients with the same stage and treatment method. After matching the original data and propensity score, logarithmic rank test and chi square test were used to evaluate the survival benefits of different stages and treatment methods for patients using Kaplan Meier curve. The prognosis of two types of cervical tumors under the same treatment method was compared, and factors that may cause poor prognosis were analyzed, excluding confounding factors. A total of 10,057 patients were included in this study, and survival analysis showed a significant correlation between the treatment method used and patient prognosis (P<0.05). However, for patients who received radiotherapy or no special treatment, OS and CSS were only related to tumor stage and not to tumor type. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients are not related to tumor pathological characteristics, while the OS of stage IIB patients is not related to tumor properties after PSM. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients were not related to histological type, while the OS of stage IIB patients was not related to histological type after PSM.

Utilizing the AJCC 8th Staging to Discriminate Survival Outcomes in HPV-associated Oropharyngeal Squamous Cell Carcinoma.

The American Joint Committee on Cancer (AJCC) staging 8th edition introduced major changes in the TNM staging of oropharyngeal squamous cell carcinoma (OPSCC) based on the human papillomavirus (HPV) status. This study aimed to observe how well the AJCC staging 8th edition precisely discriminates survival outcomes in patients with HPV-associated OPSCC using a large population database. Using the Surveillance, Epidemiology, and End Results database between 2010 and 2016, 7,448 patients with HPV-associated OPSCC were enrolled. Patients diagnosed with OPSCC and tested positive for HPV with information on the TNM staging according to the AJCC staging 7th edition were selected. Next, T-, N-, and clinical staging were reconstructed based on the AJCC staging 8th edition. Survival probabilities in both AJCC staging 7th and 8th editions were estimated and compared. Most patients (93.44%) were down-staged from the 7th to the 8th edition. The AJCC staging 8th edition showed more discriminatory power in predicting survival of patients with HPV-associated OPSCC than the AJCC staging 7th edition, regardless of the primary subsites. Additionally, clinical stage I patients with HPV-associated OPSCC according to the AJCC 8th edition showed better prognosis in case of high T staging than high N staging. Clinical staging according to the AJCC 8th edition compared to that of the 7th edition was an independent prognostic factor in patients with HPV-associated OPSCC. This study emphasizes the advantages of the new classification system for discriminating survival in HPV-associated OPSCC according to various factors.

Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Squamous Cell Carcinoma

Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Squamous Cell Carcinoma