1Dual-Gene Biology & Advantage
PAX1
squamous-sensitive · early marker
JAM3
adenocarcinoma-sensitive · aggressive phenotype
- Complementarity: PAX1 early & squamous; JAM3 aggressive & adenocarcinoma — joint detection boosts high-grade lesion detection.
- Quantitative: ΔCt-based, objective reflection of epigenetic disorder — risk, type & stage assessment.
2Assay Workflow & QC
Step 1
Sample: cervical brush / self-swab
→
Step 2
DNA + bisulfite conversion
→
Step 3
qPCR (PAX1 / JAM3)
→
Step 4
ΔCt readout & report
- Self-sampling: home vaginal swab feasible — improves compliance & access.
- Alternative: MSRE-qPCR panel (JAM3/PCDHGB7/SORCS1; PAX1/ZNF671/ASCL1) — no bisulfite, higher DNA recovery.
- QC standard: 2025 five-society expert consensus — first national clinical standard for cervical DNA methylation.
- Sample: cervical exfoliated cells — same brush & media as TCT/HPV, easy integration.
- Readout rule: ΔCt PAX1 ≤ 6.6 or ΔCt JAM3 ≤ 10.0 → positive; lower ΔCt = higher methylation.
- Clinical value: independent triage OR combined with HPV/TCT for screening.
74.1%
Se · CIN2+
95.9%
Sp · CIN2+
0.932
AUC combined
| Item | Standard |
|---|---|
| Positive | ΔCt PAX1 ≤ 6.6 or ΔCt JAM3 ≤ 10.0 |
| Sample | cervical exfoliated cells (brush / self-swab) |
| Method | bisulfite + qPCR; MSRE-qPCR alternative |
ΔCt
quantitative readout
2025
expert consensus
NMPA
approved kit context
First national clinical standard for cervical DNA methylation (2025 expert consensus) — standardized lab workflow & reporting.
3Full-Pathway Clinical Management
1
Screening
AUC 0.872 (CIN3+) vs TCT 0.580 / HPV 0.503 · CIN2+ Se 74.1% / Sp 95.9% · independent or combined (ΔCtPAX1+HPV+TCT AUC 0.932).
2
hrHPV+ triage
HPV16/18+ (n=334): Se 89.0% / Sp 95.3%, AUC 0.921 · referrals cut ~70% (1.12 per CIN2+) · 14-y cumulative cancer risk 1.7% if methylation-negative.
3
Cytology-abnormal triage
ASC-US (n=322): Se 83.8% / Sp 95.8%, referrals −79.5% · mildly abnormal: CIN3+ Se 74.9% / Sp 89.1% · CIN3+ risk 40.5% (+) vs 2.7% (−).
4
CIN2+ & post-op
ΔCt PAX1 < 4.34 → low short-term progression, may defer conization · post-op: 6-mo methylation(+) → 30.8% CIN2/3 recurrence vs <4% (−).
| Setting | Se % | Sp % | AUC | Impact |
|---|---|---|---|---|
| Screening (CIN2+) | 74.1 | 95.9 | 0.872 | beats TCT/HPV |
| HPV16/18+ (n=334) | 89.0 | 95.3 | 0.921 | referrals −70% |
| ASC-US (n=322) | 83.8 | 95.8 | — | referrals −79.5% |
| Mildly abnormal | 74.9 | 89.1 | — | risk 40.5% vs 2.7% |
−70%
HPV16/18 referrals
1.12
referrals per CIN2+
30.8%
post-op recurrence if (+)
<4%
if (−)
| Model (Sun, n=276 HSIL) | AUC |
|---|---|
| ΔCt PAX1 + HPV + TCT | 0.932 |
| ΔCt JAM3 + HPV + TCT | 0.926 |
| ΔCt PAX1 / ΔCt JAM3 | 0.867 / 0.841 |
| HPV / TCT alone | 0.791 / 0.784 |
0.932
ΔCtPAX1+HPV+TCT
0.926
ΔCtJAM3+HPV+TCT
0.867
ΔCtPAX1 alone
0.841
ΔCtJAM3 alone
Methylation complements HPV & cytology — reducing over-treatment while preserving cancer detection.