Epigenetic Biomarkers for Cervical Cancer Progression: A Scoping Review.

Cervical cancer remains the fourth most common cancer among women globally, disproportionately impacting low- and middle-income countries despite the existence of HPV vaccines. While DNA methylation has been studied extensively as a biomarker, other epigenetic mechanisms remain underexplored. This scoping review aims to report such underexplored epigenetic biomarkers linked to cervical cancer, shifting the focus beyond global nuclear DNA methylation. Literature searches were performed using Google Scholar via Publish or Perish software including studies published until January 2025. Our review focused on mitochondrial DNA, non-coding RNA, histone modifications, and repetitive elements. Mitochondrial DNA methylation has been proposed as a cervical cancer biomarker, although supporting evidence is limited. Histone modifications are more consistently reported to be involved both in cervical cancer onset and aggressiveness. Similarly, aberrant expression of lncRNAs, circRNAs, miRNAs, and piRNAs has been associated with poor prognosis. Finally, hypomethylation in repetitive elements such as LINE-1 and Alu is often observed in cervical cancer, contributing to genomic instability and tumorigenesis. Highlighting these alternative epigenetic mechanisms, our review emphasizes the importance of expanding biomarker discovery beyond the traditional nuclear DNA methylation. Understanding these mechanisms may improve early detection and personalized disease management strategies for cervical cancer.