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Objectives This hospital‐based cohort study evaluated whether ZNF582 and PAX1 methylation levels at baseline can be used as biomarkers to identify lesions with a high potential for malignant transformation in patients with normal mucosa and oral potentially malignant disorders. Patients and methods We recruited 171 adult patients with normal mucosa and oral potentially malignant disorders in 2012–2014. They were followed until 2017. Outcomes, including advanced histopathological findings and oral cancer occurrence, were obtained from medical charts, the Taiwan Cancer Registry, and cause‐of‐death data. Kaplan–Meier analysis and Cox proportional hazards regression models were used to examine the association of ZNF582 and PAX1 methylation levels at baseline with subsequent outcome occurrences. Results After 260,192 days of follow‐up, 11 cases of oral cancer and 4 cases of advanced histopathological progression occurred. Patients with higher ZNF582 and PAX1 methylation levels at baseline had a higher incidence of disease progression. After adjustment for all studied factors using Cox proportional hazards regression models, ZNF582m level (adjusted hazard ratio, 11.41; 95% CI, 2.05–63.36; p = 0.005) was the only significant and independent predictor of disease progression. Conclusions ZNF582 hypermethylation can be an effective and noninvasive biomarker for identifying oral lesions with a high potential for malignant transformation.

Background DNA methylation of paired box gene 1 (PAX1) and zinc finger 582 (ZNF582) is promising cancer biomarkers for oral squamous cell carcinoma detection. This study aims to investigate the correlation between PAX1 or ZNF582 methylation and the progression of oral squamous cell carcinoma (OSCC). Materials and Methods A total of 135 OSCC cases from Peking University School and Hospital of Stomatology were enrolled in this study. Tissue specimens were collected from the lesion site and corresponding adjacent normal site. The methylation level of these two genes was evaluated in primary and recurrent OSCC group. Results Hypermethylation of PAX1 or ZNF582 was observed in lesion sites among primary and recurrent OSCC cases. In the lesion site of primary cases, promoter methylation was observed in T3/T4 (PAX1: P = .02; ZNF582: P = .01), stage III/IV (PAX1: P = .03; ZNF582: P = .01), and bone invasion cases (PAX1: P = .02; ZNF582: P = .047). In the subgroup analysis, the correlation between hypermethylation and OSCC severity remains significant with exposure to smoking/alcohol consumption. Conclusions Hypermethylated PAX1 and ZNF582 can sufficiently act as biomarkers to reflect the severity or progression of OSCC.

Oral lichen planus (OLP) is a chronic inflammatory disease with 1%-2% prevalence depending on the global region (Gonzalez-Moles et al., 2020). The OLP clinical diagnosis requires, firstly, the presence of bilateral more or less symmetrical white lesions affecting the buccal mucosa, and/or gingiva, and/or tongue, and/or lip; secondly, the presence with white papular lesions and lace-like network of slightly raised white lines (reticular, annular or linear pattern) with/ without erosions and ulcerations; thirdly, the occasional presence of desquamative gingivitis (Warnakulasuriya et al., 2021). Some lesions mimicking OLP but not fulfilling the aforementioned criteria should be regarded as oral lichenoid lesions (OLL) (Muller, 2011).OLP with several clinical presentation (reticular, erosive, atrophic, plaque, bullous and ulcerative) altogether has been classified as potentially malignant condition or oral potentially malignant disorder (OPMD) by the World Health Organization (WHO) (Cheng,

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 (ZNF582m) 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. ZNF582m-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 ZNF582m. ROC analysis and its corresponding C-index demonstrated that either triage or co-testing models of VOE and ZNF582m 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. ZNF582m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.