China Geriatric Society · Gynecology Branch · 2025 · Expert Consensus

DNA Methylation in Cervical Cancer Screening & Triage — Consensus 2025

分子检测技术用于宫颈癌筛查和早期诊断中国专家共识（2025 年版）——甲基化应用专题
Methylation (2A): co-screening with TCT+HPV · triage HR-HPV+ / ASC-US / LSIL · WHO-endorsed future technology
China Geriatric Medical Society · Gynecology Branch
2025 年版 · 甲基化临床应用路径
2A
methylation recommendation
Co-screen
with TCT + HPV
3-way triage
HR-HPV+ · ASC-US · LSIL
WHO
future screening tech

1Consensus Position on Methylation

  • 2021 WHO (2nd ed.): DNA methylation — future molecular technology for HPV-based screening.
  • 2024 Methylation Consensus: methylation enters cervical cancer screening clinical pathway.
  • Blue Book: methylation as promising screening & triage tool.
  • 2025 Consensus: HPV & DNA methylation recommended as molecular screening (2A).

2Methylation Clinical Pathways

HR-HPV+ triage
High-risk HPV(+) women → methylation stratification → colposcopy decision.
ASC-US / LSIL
Minimally abnormal cytology → methylation triage.
TZ3 & adenocarcinoma
Type-3 transformation zone & potential adenocarcinoma risk assessment.
Post-treatment
Follow-up monitoring after cervical lesion (cancer) treatment.
Co-screening
methylation + TCT + HPV
NMPA kits
approved reagents
MSP/qPCR
detection principle
cervical cells
sample type
ΔCt
readout
HR-HPV+
triage scenario
ASC-US
triage scenario
LSIL
triage scenario
  • Result logic: methylation(+) → higher lesion risk → colposcopy; (−) → follow-up.
  • Mechanism: promoter hypermethylation silences tumor suppressors — early lesion signal.
  • Advantage: objective & repeatable — complements subjective cytology.
  • Sample: cervical exfoliated cells; same sample as TCT/HPV.
  • Regulatory: NMPA-approved kits available in China.
Triage value
HPV(+) → colposcopy decision
vs cytology
objective
vs mRNA
comparable triage
Methylation complements HPV/cytology: improves specificity of HPV(+) triage & reduces unnecessary colposcopy referrals.

3Key Methylation Recommendations

1
HPV & DNA methylation as molecular screening technologies for cervical cancer & precursors.
2A
5
Cervical-cell methylation: co-screening with TCT+HPV; triage HR-HPV+ / ASC-US / LSIL.
2A
Co-screening
TCT + HPV + methylation
Triage
HR-HPV+ · ASC-US · LSIL
Monitoring
post-treatment / TZ3

4NMPA-Approved Methylation Kits (Table 4)

PAX1 + JAM3 (CISCER)
Sample: cervical exfoliated cells · Use: qualitative detection; triage for women ≥30 y with 12 hrHPV genotypes (+); guide colposcopy.
NMPA
PAX1
Sample: cervical exfoliated cells · Use: PAX1 methylation status; triage for women ≥30 y with 13 hrHPV genotypes (+); guide colposcopy.
NMPA
SOX1 + PAX1
Sample: cervical exfoliated cells · Use: SOX1/PAX1 methylation; triage for women ≥30 y with 12 genotypes (+); guide colposcopy.
NMPA
All three kits: qualitative methylation triage for HPV(+) women ≥30 y — reduce unnecessary colposcopy.

5Methylation Evidence Highlights

78%
Se · standalone screen
>90%
Sp · standalone
96.9%
NPV · 2-yr CIN3+
Colposcopy reduction
−67%
14-yr cancer risk (M−)
1.7%
ASC-US · CCNA1 Sp
99.3%
CIN1 regression · JAM3
Se 95.2%
  • Standalone: methylation not inferior to HPV/cytology (e.g., DPP6/RALYL/GSX1).
  • Triage: beats cytology in HPV(+) (EPB41L3+JAM3 PPV/NPV 93.0/67.9 vs 60.0/25.0).
  • Progression: p16/JAM3 methylation predicts ASC-US/LSIL progression & CIN1 regression.
Clinical Significance