J Mol Diagn Ther · 2025(10) · Diagnostic Study · China

PAX1/JAM3 Methylation for Cervical Cancer Diagnosis in HR-HPV+ Women

PAX1/JAM3 基因甲基化在 HR-HPV 感染女性中宫颈癌的诊断价值
808 HR-HPV+ women · PAX1m/JAM3m: Se 86.3%, Sp 91.0%, AUC 0.873 · beats HPV16/18 (0.678) & TCT (0.608) · fewer colposcopy referrals
Feng W, Zhai Y, Meng L, Lu X, Cao Z
Beijing Obstetrics & Gynecology Hospital, Capital Medical University
PAX1m/JAM3m
AUC
0.873
Se
86.3%
Sp
91.0%
OR 51.41 (32.67–80.89)
HPV16/18
AUC
0.678
Se
76.7%
Sp
—
OR 4.46 (3.13–6.35)
TCT ≥ASC-US
AUC
0.608
Se
—
Sp
—
OR 4.13 (2.45–6.96)

1Background & Objective

  • Problem: HR-HPV DNA high sensitivity but low specificity — most infections transient → over-referral & overtreatment.
  • TCT limits: low sensitivity & subjective — over-referral and added cost.
  • Objective: evaluate PAX1m/JAM3m for cervical cancer diagnosis in HR-HPV+ women vs HPV16/18 & TCT.

2Study Design & Cohort

808
HR-HPV+ women
40y
median age
73
cervical cancer
  • Setting: Beijing Ob/Gyn Hospital, Mar 2024 – Mar 2025; guideline-based colposcopy.
  • Assays: HPV genotyping + TCT + PAX1m/JAM3m (qPCR).
  • Endpoint: cervical cancer diagnosis by pathology; ROC & OR comparison.
39.7%
Cervicitis
27.6%
CIN1
10.8%
CIN2
12.9%
CIN3
9.0%
Cancer
91.8%
PAX1m/JAM3m · cancer
87.7%
JAM3m · cancer
76.7%
HPV16/18 · cancer
Method · in cancer (n=73)Positivity
PAX1m/JAM3m91.8%
JAM3m87.7%
HPV16/1876.7%
  • Correlation: three-method comparison in cancer diagnosis — methylation strongest.
  • Severity signal: positivity rises with grade, peaking in cancer — supports triage.
Methylation positivity low in CIN2−, spikes in CIN3 & cancer — mirrors severity (Fig. 1).

3Diagnostic Performance

86.3%
Sensitivity
91.0%
Specificity
77.6%
PPV
93.5%
NPV
Positivity rates by cervical lesion grade for five methods
Fig. 1 Positivity by grade — PAX1m/JAM3m 91.8% in cancer, spikes at CIN3/cancer.
00.51.0 AUC — cervical cancer diagnosis PAX1m/JAM3m HPV16/18 TCT ≥ASC-US 0.873 0.678 0.608 methylation best · P < 0.001
Fig. AUC comparison — PAX1m/JAM3m 0.873 best.
AUC 0.873 (0.839–0.907) — best of the three methods (P<0.001).

4Referral Reduction

TCT ≥ASC-US
80.70%
HPV16/18
50.72%
PAX1m/JAM3m
43.94%
  • Referral: 43.94% — 36.76% lower than TCT, 6.78% lower than HPV16/18.
  • OR: 51.41 for cancer if methylation(+) — far stronger than HPV16/18 (4.46) / TCT (4.13).
  • Trend: methylation positivity low in CIN2−, spikes in CIN3 & cancer — an objective severity signal.
  • NPV 93.5%: methylation(−) cancer highly unlikely — safe follow-up.
  • PPV 77.6%: methylation(+) warrants colposcopy.
  • P<0.001: all OR comparisons significant.
  • Clinical fit: methylation as reflex triage in HR-HPV+ screening.
Three-method correlation confirms methylation as the strongest single cancer signal.
Clinical Significance