The Role of Methylation as an Epigenetic Marker in HPV‐Related Oral Lesions

Oral and oropharyngeal cancers, caused by persistent human papillomavirus (HPV), have recently increased. Diagnostic methods often fail to assess precancerous lesion risk, delaying oral cancer diagnosis. New molecular biomarkers, particularly DNA methylation, are sought to better stratify patients' risk. The PreCursor-M+ (Fujirebio, Tokyo, Japan), which analyze hypermethylation of the two onco-suppressor FAM19A4 and miR124-2 in cervical samples from high-risk HPV-positive women, was used to assess the methylation level of 111 oral samples distinguished in oral squamous cell carcinomas (OSCC), oral potentially malignant disorders (OPMD) benign lesions (BL), and no lesions (NL). HPV was detected by INNO-LiPA HPV Genotyping Extra II (Fujirebio, Tokyo, Japan). Hypermethylation was correlated with the severity of the diagnosis. A positive result was more common in OSCC (p < 0.0001). HPV positivity correlated with hypermethylation in OSCCs (32.4%, p = 0.0006), although statistical significance was also found in HPV-negatives (p = 0.0007). HPV16-positive OSCC showed higher methylation. Targets' methylation increased from the NL to the BL, OPMD and OSCCs groups. The methylation status of FAM19A4 and miR-124-2 may play an important role in the progression of oral cancer and, consequently, in determining the prognosis of patients with OPMD, for whom hypermethylation would suggest the need for close monitoring. Furthermore, HPV16's association with hypermethylation suggests its involvement in oral carcinogenesis. To confirm these results and gain further insight into HPV's role in methylation impairment, the sample size will be increased.