Triage Study · Ziyang Central Hospital · China

PAX1/JAM3 Methylation for Triage of hrHPV-Positive Individuals

PAX1/JAM3 甲基化在 hrHPV 阳性人群分诊中的应用价值
312 hrHPV+ patients · PAX1m/JAM3m: Se 91.8%, Sp 90.7%, AUC 0.912 · outperforms cytology & HPV16/18 genotyping · fewer colposcopy referrals
Guo Q, Wang H, Diao X, Liu Y, Chen Y, Long Q, Liu Z, Qi X, Lin S, Song X (correspondence)
Department of Laboratory Medicine, Ziyang Central Hospital
91.8%
Sensitivity · CIN2+
90.7%
Specificity · CIN2+
0.912
AUC (0.874–0.951)
1.22
referrals per CIN2+
−19.2%
colposcopy referrals

1Background & Objective

  • Problem: hrHPV+ has high false-positive rate → psychological burden, overdiagnosis & overtreatment.
  • Cytology limits: suboptimal Se/Sp; affected by sample quality & reader expertise.
  • Objective: evaluate PAX1m/JAM3m as triage for hrHPV+ individuals vs cytology & HPV16/18.

2Study Design & Cohort

312
hrHPV+ patients
2024–25
screening period
1
center
  • Assays: cervical secretions — PAX1m/JAM3m qPCR + cytology + HPV genotyping.
  • Reference: histopathology; CIN2+ endpoint.
  • Ethics: Ziyang Central Hospital (No. 2023331).

3ROC Curves

ROC curves of various methods for CIN2+
Fig. 2A ROC — PAX1m/JAM3m best for CIN2+.
ROC curves of combined methods
Fig. 2B Combined methods — methylation wins over combos.
0.912
Pm/Jm CIN2+
>
cytology
>
HPV16/18
>
combinations
  • Standalone: dual-gene methylation alone beats every single test & combination.

4Methylation Rises With Severity

PAX1m/JAM3m positivity by lesion grade
Fig. 1A Positivity increases with grade (P<.001 trend).
050%100% Dual-gene positivity by grade Normal/CIN1CIN2CIN3Cancer ≈5%≈45%≈75%≈95% derived from Fig. 1A (representative) · PAX1 normal 0% → cancer 94.4%
Fig. Dual-gene positivity rises with severity — strongest in cancer.
  • Trend: dual-gene positivity rises from normal/CIN1 to CIN3 & cancer.

5Diagnostic Performance — CIN2+

MethodSe %Sp %AUC
PAX1m/JAM3m91.890.70.912
Cytology ≥ASC-US——lower
HPV16/18(+)——lower
Methylation outperforms cytology, HPV16/18 genotyping & their combinations.

6Referral Efficiency

Cytology ≥ASC-US
ref.
PAX1m/JAM3m
−19.2%
  • 1.22 referrals / CIN2+ — efficient colposcopy triage.
  • Detection +39.4%: CIN2+ detection rate vs cytology ≥ASC-US.
  • Non-16/18: PAX1m/JAM3m(+) → CIN3+ risk 39.1%; (−) → 0.9%.
  • Resource-fit: objective qPCR suits resource-constrained settings.
Methylation triage — fewer referrals without missing high-grade lesions.
Clinical Significance