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.

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.