Head and neck squamous cell carcinoma (HNSCC) is among the most severe and complex malignant diseases with a high level of heterogeneity and, as a result, a wide range of therapeutic responses, regardless of clinical stage. Tumor progression depends on ongoing co-evolution and cross-talk with the tumor microenvironment (TME). In particular, cancer-associated fibroblasts (CAFs), embedded in the extracellular matrix (ECM), induce tumor growth and survival by interacting with tumor cells. Origin of CAFs is quite varied, and the activation patterns of CAFs are also heterogeneous. Crucially, the heterogeneity of CAFs appears to play a key role in ongoing tumor expansion, including facilitating proliferation, enhancing angiogenesis and invasion, and promoting therapy resistance, through the production of cytokines, chemokines, and other tumor-promotive molecules in the TME. This review describes the various origin and heterogeneous activation mechanisms of CAFs, and biological heterogeneity of CAFs in HNSCC is also included. Moreover, we have highlighted versatility of CAFs heterogeneity in HNSCC progression, and have discussed different tumor-promotive functions of CAFs respectively. In the future, it is a promising strategy for the therapy of HNSCC that specifically targeting tumor-promoting CAF subsets or the tumor-promoting functional targets of CAFs.

Circular RNAs are abundant endogenous non-coding RNA with no 5′ cap and 3′ polyadenylation tail that modify liner mRNAs and have no terminal structures. Our knowledge of the biogenesis of circular RNAs has been expanded, and circular RNAs were shown to be key regulators of various diseases, especially cancers. Head and neck cancers are the sixth most popular cancers worldwide, and the overall survival rates remain unsatisfactory. Recent studies have indicated that circular RNAs are involved in the tumorigenesis, progression, invasion and chemosensitivity of head and neck cancers and that some circular RNAs could serve as diagnostic and prognostic biomarkers. In this study, we summarize research advances in the regulation of circular RNA biogenesis, their characteristics and functions, the involvement of circular RNAs in the pathophysiology of head and neck cancers and their potential clinical utilization, as well as the likely directions of future studies.

Exosomes are nanometer‑scale extracellular vesicles derived from almost all types of cells and key signaling mediators between cancer cells and their microenvironment. Certain microRNAs (miRNAs) are selected for exosome packing and exclusion from parental cells, while other miRNAs are selectively retained by cells, suggesting a biological role for these miRNAs in tumor malignant progression. In the present study, we isolated and characterized the exosomes derived from the laryngeal squamous cell carcinoma (LSCC) cell line AMC‑HN‑8 for the first time, and identified a subset of miRNAs enriched in the exosomes compared with parental cells, such as miR‑1246, miR‑1290, miR‑335‑5p, miR‑127‑3p and miR‑122‑5p through small RNA sequencing combined with reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Potential target prediction, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed possible functions associated with these selective exosomal miRNAs. In conclusion, the present study demonstrated that the LSCC cell line AMC‑HN‑8 can release exosomes and cells can selectively pack certain miRNAs into exosomes.

Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that high enrichment of Fusobacterium nucleatum (F. nucleatum) in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B (ADH1B) and transforming growth factor β receptor 2 (TGFBR2) expression by activating innate immune signaling, resulting in ethanol metabolism reprogramming to allow F. nucleatum accumulation and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition, further exacerbating the uncontrolled progression and metastasis of LSCC. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, which yields valuable insight into clinical management that may improve the oncologic outcome of patients with LSCC.