Objective To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR). Data Sources PubMed, Cochrane Library, and Scopus. Methods A comprehensive review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature. Conclusions The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance–pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved. Implications for Practice The development of multichannel intraluminal impedance–pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.

In this study we assessed the clinical significance of an epithelial-mesenchymal transition (EMT) gene signature and explored its association with the tumor microenvironment related to immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Genes were selected when mRNA levels were positively or negatively correlated with at least one well-known EMT marker. We developed an EMT gene signature consisting of 82 genes. The patients were classified into epithelial or mesenchymal subgroups according to EMT signature. The clinical significance of the EMT signature was validated in three independent cohorts and its association with several immunotherapy-related signatures was investigated. The mesenchymal subgroup showed worse prognosis than the epithelial subgroup, and significantly elevated PD-1, PD-L1, and CTLA-4 levels, and increased interferon-gamma, cytolytic, T cell infiltration, overall immune infiltration, and immune signature scores. The relationship between PD-L1 expression and EMT status in HNSCC after treatment with TGF-β was validated in vitro. In conclusion, the EMT gene signature was associated with prognosis in HNSCC. Additionally, our results suggest that EMT is related to immune activity of the tumor microenvironment with elevated immune checkpoint molecules. Epithelial-mesenchymal transition (EMT) refers to a process whereby the adhesive polarity of epithelial cancer cells dissipates and changes to mesenchymal cells. This occurs in conjunction with increased cell migration and invasiveness and is also known to play an important role in cytoskeletal remodeling and resistance to apoptosis 1. Several studies have reported the association of EMT activation with cancer metastasis, resistance to anticancer drugs, and thus a poor prognosis 2-4. Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer worldwide, with mortality rates of 40-50% despite advances in radiation and surgical treatments 5. Radiotherapy and cytotoxic chemotherapy for HNSCC are associated with substantial toxicity and morbidity. There is no biomarker that can predict response to treatments, such as radiotherapy, chemotherapy, and especially immunotherapy in patients with HNSCC. Immunotherapy has begun a new era in cancer treatment by using treatments such as checkpoint inhibitors that target the host immune system instead of tumors 6. Immune checkpoint inhibitors have showed promising preliminary data and were approved for use by the FDA in patients with advanced HNSCC 7-9. Few studies have reported the impact of EMT on the interactions between cancer and immune cells. We sought to develop an EMT gene signature that can predict prognosis by systematically analyzing genomic data from several independent cohorts of patients with HNSCC. In addition, we analyzed the association between EMT gene signatures and several immunotherapy-related gene signatures with the aim of determining whether the activation status of EMT signatures corresponds to the tumor microenvironment related to immunotherapy.

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The efficacies of both treatments were similar. The rate of adverse effects was significantly lower for intralesional injection of TA than mouth rinse of TA.

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