J Cent South Univ (Med Sci) · 2023;48(12):1820–1829 · China

JAM3/PAX1 Hypermethylation for HSIL Diagnosis in hrHPV+ Women

高危型人乳头瘤病毒感染患者宫颈脱落细胞 JAM3/PAX1 高甲基化诊断宫颈高级别病变
136 hrHPV+ women (122 non-HSIL + 14 HSIL) · methylation stratifies independently of LBC · ΔCtP >6.22 → 97.5% non-HSIL · ΔCtJ correlation r = −0.448
Li X, He S, Zhao X, Sun D, Wu S, Xu D, Li Y
Xiangya 3rd Hospital, Central South University · 中南大学学报(医学版)2023;48(12):1820–1829
136
hrHPV+ women
r = −0.448
ΔCtJ vs lesion (P<0.001)
97.5%
non-HSIL if ΔCtP >6.22
LBC-free
independent stratification

1Background & Objective

  • Limits of hrHPV/LBC: hrHPV low specificity; LBC sensitivity 50–80% & subjective ASC-US reads.
  • Objective: evaluate JAM3/PAX1 methylation vs LBC for HSIL — alone or combined.

2Study Design & Cohort

122
non-HSIL
14
HSIL
2021.6–22.6
colposcopy clinic
ΔCtP
group difference P<0.05
ΔCtJ
group difference P<0.05
LBC
group difference P<0.05
  • Inclusion: confirmed histology; LBC+hrHPV+colposcopy; sexual history; no treatment in 6 mo.
  • Exclusion: menstruation; known genital cancer; autoimmune/immunosuppression; pregnancy/lactation; HPV vaccination.
  • Design: retrospective, Xiangya 3rd Hospital colposcopy clinic.
  • Assays: LBC · hrHPV · histopathology · vaginal microecology · ΔCtP/ΔCtJ.
  • Model: conditional inference tree (R party) for classification.
  • Statistics: t-test / Wilcoxon · χ² / Fisher · Pearson correlation.
NS
age · BMI · HPV type
NS
menopause · TZ type
0.037
flora diversity P
  • Variables: demographics · LBC · hrHPV · histology · microecology · colposcopy TZ · ΔCtJ/ΔCtP.
Correlation heatmap of clinical parameters
Fig. Correlation heatmap — pathology negatively linked to ΔCtP, ΔCtJ, LBC, flora diversity.
Ethics No. 23137 · Hunan Clinical Innovation Project 2020SK53604.

3Correlations with Lesion Grade

ΔCtJ
r = −0.448
ΔCtP
r = −0.360
LBC grade
r = −0.305
Flora diversity
r = −0.183
  • Methylation ↑ (ΔCt ↓) tracks HSIL — stronger than LBC; age/BMI/HPV type & menopause ns.

4Conditional Inference Tree & Decision Rules

Conditional inference tree for HSIL diagnosis
Fig. Tree splits on ΔCtJ → ΔCtP → LBC — gray = non-HSIL, black = HSIL (probability 0–1).
ΔCtJ >10.13
100% non-HSIL — safe deferral
ΔCtP >6.22
97.5% non-HSIL (117/120)
ΔCtJ >8.61 + ASC-US/NILM
99.1% non-HSIL
ΔCtJ ≤8.61
20 (9/11)
non/HSIL ~1:1
8.61 < ΔCtJ ≤10.13
12 (9/3)
HSIL falls
ΔCtJ >10.13
104 (104/0)
all non-HSIL
ΔCtP ≤6.22
16 (5/11)
mostly HSIL
ΔCtP >6.22
120 (117/3)
97.5% non-HSIL
LBC = HSIL
9 (3/6)
3 non / 6 HSIL
  • Negative rule out: high ΔCt safely excludes HSIL — fewer colposcopies.
  • ≥ LBC alone: methylation alone not inferior to combined LBC models.
  • Add-on: improves LBC accuracy; objective & self-sampling friendly.
Clinical Significance