China · 7 Societies · Clinical Guideline · Abnormal-Result Triage

Guidelines for Cervical Cancer Screening in China (II) — Triage

中国子宫颈癌筛查指南(二)——筛查异常的分流管理
Cytology primary triage (1类) · p16/Ki-67 dual stain (2A) · methylation for 12 HR-HPV (2B) · HPV integration (2B)
CSCCP · CGCS · CFC · CMCHS · CSGO-CMA · CMIHE · CPMA
7 Chinese medical societies · Part II: triage of abnormal screening results
Cytology
primary triage · 1类
Dual stain
p16/Ki-67 · 2A
Methylation
12 HR-HPV triage · 2B
HPV integration
HR-HPV triage · 2B

1Background & Goal

  • Goal: standardize triage of abnormal results — avoid overdiagnosis AND missed diagnosis.
  • Burden: 150,700 new & 55,700 deaths in China 2022 (22.7%/16.0% of world).
  • Context: builds on Screening Guideline (I); WHO elimination strategy.

2Triage Methods Overview

1
Cytology — main triage for HR-HPV(+) primary screening.
1类
2
p16/Ki-67 dual stain — HPV(+) no-genotype / 12 HR-HPV; co-test NILM/ASC-US/LSIL.
2A
3
Methylation — triage of 12 HR-HPV(+) to reduce colposcopy referrals.
2B
4
HPV integration — HR-HPV(+) triage; positive → colposcopy.
2B
  • Reagents: all new methods need authoritative approval & validated indications.
  • Others: extended genotyping / viral load — more evidence needed.
76.6%
HPV16 in SCC
7.9%
HPV18 in SCC
3.2%
HPV31 in SCC
35.1%
HPV16 in adeno
30.6%
HPV18 in adeno
74.5%
hrHPV in adeno
52/58/16
CIN1 common types
16/58/52/33/31
CIN2/3+ types
15.0%
HPV prevalence ≥20 y
  • Why triage: HPV(+) mostly transient — triage spares low-risk women from colposcopy.
  • Risk principle: same risk, same management (ASCCP).
  • Dual stain scope: HPV(+) no-genotype / 12 HR-HPV; co-test NILM/ASC-US/LSIL.
  • Methylation mechanism: CpG promoter methylation silences suppressors — triage signal.
  • Integration mechanism: HPV DNA integration into host genome — risk stratifier.
  • Reagent gate: authoritative approval + clinically validated indications for each method.
Refined triage = precision management: fewer unnecessary colposcopies, fewer missed lesions; cytology remains the workhorse, molecular methods add precision.

3Management Flowcharts (Fig 1–4)

Fig1 HPV primary screening abnormal management
Fig 1 · HPV(+) primary screening
No-genotype → cytology triage or genotyping · 16/18+ → colposcopy · 12 HR-HPV+ → cytology triage.
Fig2 cytology primary screening abnormal management
Fig 2 · Cytology(+) primary screening
ASC-US/LSIL → HPV-based triage · ASC-H/HSIL/AGC → colposcopy · SCC/adeno → immediate referral.
Fig3 co-testing abnormal management
Fig 3 · Co-testing abnormal
Risk-based per ASCCP 2019: combine HPV & cytology strata to decide colposcopy vs follow-up.
Fig4 dual stain triage
Fig 4 · p16/Ki-67 dual stain
DS(+) → colposcopy · DS(−) → 1-yr follow-up (HR-HPV no-genotype / 12 HR-HPV; co-test NILM/ASC-US/LSIL).
Four management flows cover HPV-primary, cytology-primary, co-testing and dual-stain triage pathways.

4Methylation Triage (2B) & HPV Integration

12 HR-HPV+
methylation triage target
colposcopy ↓
referral reduction
2B
recommendation class
  • Methylation: CpG-island promoter hypermethylation silences tumor suppressors — early lesion signal for triage.
  • Reagents: approved & clinically validated for 12 HR-HPV(+) triage.
  • HPV integration: integration(+) → high-risk, full colposcopy & histology; (−) → 1-yr follow-up.
Clinical Significance