Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions.

MiR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated deaths worldwide. Family members in miR-371/372/373 miRNA cluster, which is localized at human chromosome 19q13.4, are co-expressed in both human stem cells and malignancies. The individual miRNA in this cluster are also involved in modulating the pathogenesis of malignancies as either oncogenes or suppressors. The 19q13 region is frequently gained in head and neck cancers. High expression of miR-372 and miR-373 are survival predictors for OSCC. However, the role of the miR-371/372/373 cluster in oral carcinogenesis remains to be fully investigated. We use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system to establish OSCC cell subclones that had the miR-371/372/373 cluster deleted. In addition, further subclones were established that had the promoter of this cluster deleted. Concordant silencing in SAS cells of miR-371/372/373 decreased oncogenic potential, increased cisplatin sensitivity, activated p53, and upregulated the expression of Bad and DKK1. We also employed the CRISPR/dCas9 synergistic activation mediator system, which allowed robust transcriptional activation of the whole miR-371/372/373 cistron. Upregulation of endogenous miR-371/372/372 expression increased both oncogenicity and drug resistance. These were accompanied by a slight activation of AKT, β-catenin, and Src. This study identifies the oncogenic role of the miR-371/372/373 cluster in OSCC. Using CRISPR based strategy can be a powerful paradigm that will provide mechanistic insights into miRNA cluster functionality, which will also likely help the development of targeting options for malignancies.

Dysbiosis of oral microbiome causes chronic diseases including dental caries and periodontitis, which frequently affect older patient populations. Severely disabled individuals with impaired swallo...

Cisplatin resistance poses a major challenge in the treatment of oral squamous cell carcinoma (OSCC). Deeper investigations into the mechanisms underlying this drug resistance is of great importance. Here, we used cellular assays and clinical immunohistochemistry to examine molecular pathways involved in both innate and acquired cisplatin resistance. We demonstrated that the p62-mTORC1 signaling complex plays a pivotal role, and is driven by the EGFR signaling network, specifically through the PI3K-Akt axis and the transcription factor C/EBP-β. Elevated p-mTOR expression was associated with cancer relapse and poor prognosis among oral cancer patients. Additionally, we illustrated that mTOR inhibitors enhance the cytotoxic effect of cisplatin, by employing cancer stem cell characteristics. Our work unveils fundamental mechanisms for cisplatin resistance, thereby presenting therapeutic implications for OSCC.

Background: Visual oral examination (VOE) is a conventional oral cancer screening method. This study aimed to evaluate the value of methylation marker to assist VOE in identifying oral epithelial dysplasia and oral squamous cell carcinoma (OED/OSCC) from non-cancerous lesions in a real-world situation. Methods: 201 patients with high-risk personal habits who self-perceived oral anomaly were VOE examined, ZNF582 methylation (ZNF582^m) tested, and histologically diagnosed. Results: Among them, 132 patients (65.7%) were histologically diagnosed OED/OSCC. Using VOE, 56.1% OED/OSCC patients had possible oral cancer, whereas 37.7% non-OED/OSCC patients had leukoplakia. ZNF582^m-positive was detected in 90.2% OED/OSCC patients and 44.9% non-OED/OSCC patients. Various logistic regression models were postulated to evaluate the diagnostic performance of conventional VOE and new strategies using ZNF582^m. ROC analysis and its corresponding C-index demonstrated that either triage or co-testing models of VOE and ZNF582^m could improve diagnostic performance and discriminative abilities compared with the VOE only approach. Conclusions: In conclusion, methylation marker test shows equivalent performance to an experienced judgment by oral maxillofacial surgeons and plays a significantly supplementary role in increasing the efficacy in identifying oral malignant lesions. ZNF582^m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.