DNA Methylation in Cervical Intraepithelial Neoplasia and Cervical Cancer: Triage and Management

This chapter discusses the role of DNA methylation, an epigenetic mechanism that regulates gene expression, as a key event in cervical carcinogenesis, and highlights its potential as a biomarker for detecting cervical cancer and high-grade precancerous lesions. Methylation levels of specific genes (methylation markers) gradually increase with cervical disease severity, allowing several clinical applications. Methylation markers have been evaluated as alternative triage tools for high-risk (hr) human papillomavirus (HPV)-positive women, including those with borderline or mildly abnormal cytology results, and for use in specific populations such as women living with HIV. Methylation testing often outperforms traditional cytology-based triage methods and offers long-term reassurance against cervical cancer when the result is negative. Additionally, methylation markers have shown prognostic potential in predicting the natural course of high-grade precancerous lesions, as well as a promising performance for the detection of recurrent disease. While ongoing research focuses on validating methylation testing in self-collected samples, low-resource settings, and HPV-vaccinated populations, current evidence supports its potential to enhance early detection, risk stratification, and post-treatment monitoring in cervical cancer prevention and care.