Chin J Lab Med · 2026;49(2) · Cross-Sectional · China

Vaginal Microecology, PAX1/JAM3 Methylation & Cervical Lesions

阴道微生态影响宫颈细胞 DNA 甲基化水平与宫颈病变的相关性研究
492 women · microecology & methylation differ by lesion grade · L. crispatus protective · PAX1m/JAM3m correlate with grade · full mediation via PAX1 methylation
Wu S, Lv W, Zhao X, Ma J, Xu D, Zhang D
Xiangya 3rd Hospital, Central South University · 中华检验医学杂志 · 2026;49(2):172–180
492
women
4
lesion groups
OR 0.871
ΔCtJ per grade (P<0.001)
−0.099
mediation effect

1Background & Objective

  • Question: does vaginal microecology influence cervical lesions via DNA methylation?
  • Objective: correlate microecology, PAX1/JAM3 methylation & lesion grade; test mediation.

2Study Design & Cohort

81
HPV/TCT(−)
236
chronic inflam.
117
LSIL
58
HSIL
81
HPV/TCT(−)
236
chronic inflam.
117
LSIL
58
HSIL
BMI
differs (neg. group highest)
孕次
parity differs
16/18
HPV16/18 ↑ in HSIL
  • Setting: Xiangya 3rd Hospital, Apr 2022 – Aug 2024; cross-sectional.
  • Grouping: HPV/TCT + colposcopy biopsy pathology → 4 ordered groups.
  • Samples: vaginal swab (qualitative flora) + cervical cells (PAX1/JAM3 ΔCt).
  • Microecology panel: density · diversity · Nugent · pH · dominant flora · leukocyte esterase · lactobacilli.
  • Analysis: ANOVA / Kruskal-Wallis · ordinal logistic · linear regression · mediation (Process 4.1, 5000 boot).
  • Outcome: lesion grade ordered from negative → chronic inflammation → LSIL → HSIL.
  • Groups: only non-negative groups were hrHPV+, HSIL with more HPV16/18.
  • Statistics: LSD pairwise · Pearson χ² · Spearman; mediation bootstrap 5000.
ΔCtP by grade
P<0.001 ↓
ΔCtJ by grade
P<0.001 ↓
Lower ΔCt = higher methylation; both increase with lesion grade.

3Microecology Differs by Grade

  • Dysbiosis markers: density, diversity, Nugent, pH, dominant flora, leukocyte esterase — differ across groups (P<0.05).
  • Lactobacillus: L. iners & L. crispatus detection differ (P<0.05) — L. crispatus protective.
pH ↑ with grade
↑
L. crispatus
protective ↓

4Mediation — the Key Finding

−0.099
mediation effect
−0.170 ~ −0.039
95% CI (excludes 0)
0.906
OR via mediator
−9.4%
risk per SD of ΔCtP
L. crispatus (+) protective flora PAX1 methylation ΔCtP ↓ = hypermethylation Lesion grade neg → inflam → LSIL → HSIL β pos · P=0.049 flora ↓ methylation β −0.075 · OR 0.928 methylation ↑ grade direct effect ns (−0.101, 95%CI −0.266~0.063) → full mediation
  • Full mediation: L. crispatus acts through PAX1 methylation (OR 0.906); direct effect ns.
  • Mechanism: protective flora ↑ → methylation ↓ → lower lesion risk.

5Risk Factors & Methylation Drivers

Parity (per grade)
OR 1.136
ΔCtJ (per grade)
OR 0.871
ΔCtP (per grade)
OR 0.928
L. crispatus (+)
OR 0.523
  • Methylation drivers: older age & hrHPV (esp. 16/18) raise PAX1/JAM3 methylation.
Clinical Significance