Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Tumor mutational burden predictability in head and neck squamous cell carcinoma patients treated with immunotherapy: systematic review and meta-analysis.

BACKGROUND: Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head and neck squamous cell carcinoma (HNSCC) has not yet been specifically addressed. Since HNSCC patients exhibit a rather limited response to ICIs, there is an unmet need to develop predictive biomarkers to improve patient selection criteria and the clinical benefit of ICI treatment. METHODS: We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. HNSCC cohort studies were selected when TMB prior to ICI treatment was evaluated, TMB cutoff value was available, and the prognostic value of TMB was evaluated by time-to-event survival analysis. A total of 11 out of 1960 articles were analyzed, including 1200 HNSCC patients. RESULTS: The results showed that those patients harboring high TMB exhibited a significantly superior overall response rate (OR = 2.62; 95% CI 1.74-3.94; p < 0.0001) and a survival advantage (HR = 0.53; 95% CI 0.39-0.71; p < 0.0001) after ICI treatment. CONCLUSION: This is the first meta-analysis to demonstrate a higher response and clinical benefit from ICI therapy in HNSCC patients with high TMB.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

BACKGROUND: There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. METHODS: We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. RESULTS: High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. CONCLUSIONS: Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

Dissecting the functions of cancer-associated fibroblasts to therapeutically target head and neck cancer microenvironment.

Head and neck cancers (HNC) are a diverse group of aggressive malignancies with high morbidity and mortality, leading to almost half-million deaths annually worldwide. A better understanding of the molecular processes governing tumor formation and progression is crucial to improve current diagnostic and prognostic tools as well as to develop more personalized treatment strategies. Tumors are highly complex and heterogeneous structures in which growth and dissemination is not only governed by the cancer cells intrinsic mechanisms, but also by the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) emerge as predominant TME components and key players in the generation of permissive conditions that ultimately impact in tumor progression and metastatic dissemination. Although CAFs were initially considered a consequence of tumor development, it is now well established that they actively contribute to numerous cancer hallmarks i.e., tumor cell growth, migration and invasion, cancer cell stemness, angiogenesis, metabolic reprograming, inflammation, and immune system modulation. In this scenario, therapeutic strategies targeting CAF functions could potentially have a major impact in cancer therapeutics, providing avenues for new treatment options or for improving efficacy in established approaches. This review is focused on thoroughly dissecting existing evidences supporting the contribution of CAFs in HNC biology with an emphasis on current knowledge of the key molecules and pathways involved in CAF-tumor crosstalk, and their potential as novel biomarkers and/or therapeutic targets to effectively interfere the tumor-stroma crosstalk for HNC patients benefit. involved in CAF-tumor crosstalk, and their potential as novel biomarkers and/or therapeutic targets to effec- tively interfere the tumor-stroma crosstalk for HNC patients benefit.

The effect of bariatric surgery on metabolic syndrome: A retrospective cohort study in Colombia.

Introduction and Objective: Metabolic syndrome (MetS) represents a group of metabolic abnormalities. It is currently a pandemic, and its prevalence is on the rise. MetS has a direct relationship with obesity, for this reason, bariatric and metabolic surgery has been proposed as a method to simultaneously control obesity and MetS. However, in Colombia the results of this intervention are unknown. This study aims to compare metabolic syndrome before and after bariatric surgery in a Colombian population. Methods: Retrospective cohort study conducted in a highly complex institution in Colombia, where comparing the prevalence of metabolic syndrome in patients who underwent bariatric surgery during a 1-year follow-up period, between January 2015 and December 2019. Of these patients, 48 underwent Roux-en-Y gastric bypass, and 32 underwent sleeve gastrectomy by laparoscopic technique. Results: A total of 80 patients were included, of which 67.5% were women and the mean age was 42.8 ± 12.9 years. The most frequent preprocedure comorbidities were arterial hypertension (36.2%), dyslipidemia (32.4%), and sleep apnea (20%). After bariatric surgery, the prevalence of metabolic syndrome decreased from 66.2% to 3.7% (p < 0.05). In addition, a reduction in the Homeostatic Model Assessment for Insulin Resistance score from 77.5% to 22.5% was observed during the follow-up period. HbA1c, creatinine, and thyroid-stimulating hormone, were the only parameters without significant changes. Conclusions: Metabolic and bariatric surgery is an effective treatment for weight reduction, with a high impact in reducing the prevalence of metabolic syndrome and insulin resistance in the short and medium term in the Colombian population.

Tumor-Intrinsic Nuclear ß-Catenin Associates with an Immune Ignorance Phenotype and a Poorer Prognosis in Head and Neck Squamous Cell Carcinomas.

Activation of WNT/ß-catenin signaling has been associated with a non-T-cell-inflamed tumor microenvironment (TME) in several cancers. The aim of this work was to investigate the relationship between ß-catenin signaling and TME inflammation in head and neck squamous cell carcinomas (HNSCCs). Membrane and nuclear ß-catenin expression, PD-L1 expression, and CD8+ tumor-infiltrating lymphocyte (TIL) density were jointly evaluated by immunohistochemistry in a series of 372 HPV-negative HNSCCs. Membrane ß-catenin levels decreased in carcinomas compared to the normal epithelium. Positive nuclear ß-catenin was detected in 50 tumors (14.3%) and was significantly associated with a low CD8+ TIL density (168 cells/mm2 versus 293 cells/mm2 in nuclear-ß-catenin-negative cases; p = 0.01) and a tendency for a lower expression of PD-L1, resulting in association with a noninflamed TME (i.e., type II, immunological ignorance). Multivariate Cox analysis further demonstrated that low infiltration by CD8+ TILs (HR = 1.6, 95% CI = 1.19-2.14, p = 0.002) and nuclear ß-catenin expression (HR = 1.47, 95% CI = 1.01-2.16, p = 0.04) were both independently associated with a poorer disease-specific survival. In conclusion, tumor-intrinsic nuclear ß-catenin activation is associated with a non-inflamed TME phenotype and a poorer prognosis, thereby suggesting a possible implication as an immune exclusion mechanism for a subset of HNSCC patients.

Pathobiological functions and clinical implications of annexin dysregulation in human cancers.

Annexins are an extensive superfamily of structurally related calcium- and phospholipid-binding proteins, largely conserved and widely distributed among species. Twelve human annexins have been identified, referred to as Annexin A1-13 (A12 remains as of yet unassigned), whose genes are spread throughout the genome on eight different chromosomes. According to their distinct tissue distribution and subcellular localization, annexins have been functionally implicated in a variety of biological processes relevant to both physiological and pathological conditions. Dysregulation of annexin expression patterns and functions has been revealed as a common feature in multiple cancers, thereby emerging as potential biomarkers and molecular targets for clinical application. Nevertheless, translation of this knowledge to the clinic requires in-depth functional and mechanistic characterization of dysregulated annexins for each individual cancer type, since each protein exhibits varying expression levels and phenotypic specificity depending on the tumor types. This review specifically and thoroughly examines the current knowledge on annexin dysfunctions in carcinogenesis. Hence, available data on expression levels, mechanism of action and pathophysiological effects of Annexin A1-13 among different cancers will be dissected, also further discussing future perspectives for potential applications as biomarkers for early diagnosis, prognosis and molecular-targeted therapies. Special attention is devoted to head and neck cancers (HNC), a complex and heterogeneous group of aggressive malignancies, often lately diagnosed, with high mortality, and scarce therapeutic options.

Utilidad de la evaluación USG Doppler de las arterias uterinas entre las semanas 11 y 13+6 y su aplicación en las calculadoras de riesgo para predecir preeclampsia / Usefulness of the USG Doppler evaluation of the uterine arteries between weeks 11 and 13+6 and its application in risk calculators to predict preeclampsia / Utilidade da avaliação USG Doppler das artérias uterinas entre as semanas 11 e 13+6 e sua aplicação em calculadoras de risco para prever pré-eclâmpsia

Introducción. La preeclampsia es la primera causa de muerte materna directa en Colombia y la segunda a nivel mundial. El desarrollo de estrategias de predicción y prevención puede disminuir las complicaciones y secuelas ocasionadas por dicha enfermedad. El Doppler de arterias uterinas entre las semanas 11 y 13+6 como prueba independiente o en combinación con factores maternos o pruebas bioquímicas permite tasas de detección de preeclampsia temprana ≥ 90% a partir de la implementación de distintos cribados. La validez de dicha prueba diagnóstica presenta una sensibilidad del 47.8% y especificidad del 92.1% para la detección de preeclampsia temprana; con una sensibilidad del 26.4% y especificidad del 93.4% para predecir preeclampsia en cualquier etapa. División de los temas tratados. En esta revisión de tema se aborda la utilidad de esta medición, se habla de la realización de la técnica en cuestión y, por último, se revisan las herramientas estandarizadas que están disponibles en la actualidad junto con su accesibilidad y precisión. Conclusiones. La evidencia empírica que respalda la validez de las herramientas disponibles hoy en día para el tamizaje de preeclampsia a través de la evaluación por ultrasonografía Doppler de las arterias uterinas es significativa. Al ser Colombia un país que presenta una prevalencia alta de preeclampsia, conocer la utilidad de esta medición favorece una vigilancia temprana y oportuna, lo que disminuye los posibles desenlaces desfavorables para las maternas.

Introduction. Preeclampsia is the primary cause of direct maternal death in Colombia and the second globally. The development of prediction and prevention strategies can reduce complications and consequences caused by this disease. The uterine arteries Doppler between weeks 11 and 13+6 as an independent test or in combination with maternal factors or biochemical tests allows for early detection rates for preeclampsia of ≥90% from the implementation of different sieving. The validity of this diagnostic test has a sensitivity of 47.8% and specificity of 92.1% for the early detection of preeclampsia; with a sensitivity of 26.4% and specificity of 93.4% to predict preeclampsia at any stage. Division of Covered Topics. This topic review covers the usefulness of this measurement. It discusses the performance of the technique in question and, lastly, the standardized tools currently available are reviewed together with the accessibility and accuracy. Conclusions. The empirical evidence that supports the validity of the tools available today for the screening of preeclampsia via Doppler ultrasound evaluation of the uterine arteries is significant. As Colombia is a country with a high prevalence of preeclampsia, knowing the usefulness of this measurement favors early and timely surveillance, which reduces possible unfavorable outcomes for mothers.

Introdução. A pré-eclâmpsia é a principal causa de morte materna direta na Colômbia e a segunda no mundo. O desenvolvimento de estratégias de predição e prevenção pode reduzir as complicações e sequelas causadas pela doença. O Doppler da artéria uterina entre as semanas 11 e 13+6 como um teste independente ou em combinação com fatores maternos ou testes bioquímicos permite taxas de detecção de pré-eclâmpsia precoce≥90% a partir da implementação de diferentes exames. A validade desse teste diagnóstico tem sensibilidade de 47,8% e especificidade de 92,1% para a detecção de pré-eclâmpsia precoce; com uma sensibilidade de 26,4% e especificidade de 93,4% para prever pré-eclâmpsia em qualquer fase. Divisão dos tópicos abordados. Esta revisão de tópicos aborda a utilidade desta medição, discute a realização da técnica em questão e, por fim, são revisadas as ferramentas padronizadas que estão disponíveis atualmente, juntamente com sua acessibilidade e precisão. Conclusões. A evidência empírica que apoia a validade das ferramentas disponíveis atualmente para rastreamento de pré-eclâmpsia por meio da avaliação de ultrassom Doppler das artérias uterinas é significativa. Como a Colômbia é um país com alta prevalência de pré-eclâmpsia, conhecer a utilidade dessa medição favorece a vigilância precoce e oportuna, o que reduz possíveis resultados desfavoráveis para mulheres maternas.