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High-Throughput Targeted Sequencing Identifies an HPV Methylation Panel for Detecting Cervical Lesion Progression
Hui Liu1, Jie Zhou2, Yunxia Xiao3
1Department of Pathology, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital Northwest University, Xi'an, Shaanxi, China.
Journal of Medical Virology
|December 8, 2025
Summary
Quantitative methylated HPV DNA markers show promise for precisely detecting cervical lesions. A novel five-CpG methylation panel effectively distinguishes cervical cancer precursors in HPV16-positive women.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- High-risk human papillomavirus (hrHPV) infection is the primary cause of cervical cancer.
- Current hrHPV testing lacks specificity for detecting neoplastic changes, necessitating improved diagnostic tools.
Purpose of the Study:
- To explore the utility of quantitative methylated HPV DNA markers for precise detection of cervical lesions.
- To identify novel HPV16 methylation markers capable of distinguishing cervical lesions from normal tissue.
Main Methods:
- Genome-wide HPV methylation patterns were analyzed using hybridization capture-based bisulfite sequencing.
- A training cohort (60 samples) and a validation cohort (29 samples) were utilized.
- Analysis focused on 112 CpG sites across the HPV genome, correlating methylation levels with disease progression.
Main Results:
- Genome-wide HPV16 methylation levels correlated significantly with cervical cancer progression (SCC vs. normal tissue, p=0.0032).
- Progressive methylation increases were observed in E5-α and L2 genes across lesion severity.
- A five-CpG methylation panel demonstrated high discriminatory performance (AUC=0.919) in a validation cohort for detecting cervical lesions.
Conclusions:
- Novel HPV16 methylation markers were identified that distinguish cervical lesions from normal tissue.
- A five-CpG methylation panel shows promise as a triage biomarker for HPV16-positive women in cervical cancer screening.
- HPV methylation-based triage is feasible for improving cervical cancer screening accuracy.
