BMC Women's Health · Multinomial Logistic Regression

Association of PAX1/JAM3 Methylation, HR-HPV & TCT with High-Grade Cervical Lesions

高危队列中 PAX1/JAM3 基因甲基化、HR-HPV 与 TCT 与宫颈高级别病变的相关性
409-woman colposcopy-referred cohort · multinomial logistic regression · JAM3 OR 8.215
Geng T, Li S (co-first), Bian Y, Li X, Bian Y · First Hospital of Hebei Medical University
BMC Women's Health 2026 · DOI 10.1186/s12905-026-04622-9 · Published 25 Jun 2026
409
high-risk cohort
8.215
JAM3 OR (HSIL)
4.145
PAX1 OR (HSIL)
36.2%
HSIL prevalence

1Background & Objective

132.8千
China new cases 2022
49.8千
deaths 2022
TCT
resource-limited scale
  • Foundation: HR-HPV + TCT is the backbone of screening, but TCT needs equipment/personnel and HPV over-refers.
  • Methylation: PAX1/JAM3 reflect host transforming infection — a candidate objective marker.
  • Aim: identify independent risk factors for LSIL and HSIL progression in a high-risk cohort.

2Methods & Cohort

2023.1–2025.4
enrollment
39 y
median age
78%
premenopausal
  • Cohort: colposcopy-directed biopsy for abnormal TCT, HR-HPV or positive PAX1/JAM3 methylation.
  • Pathology: Inflammation 168 (41.1%) · LSIL/CIN1 93 (22.7%) · HSIL/CIN2-3 148 (36.2%).
  • Markers: HR-HPV (other 46.0% · 16/18 46.5%) · non-NILM TCT 44.3% · PAX1+ 14.4% · JAM3+ 17.6%.
  • Statistics: multinomial logistic regression (proportional-odds violated, P=0.024); LR χ²=145.916; VIF <5.
14.4%
PAX1+
17.6%
JAM3+
46.5%
HPV16/18+
41.1%
inflammation
22.7%
LSIL/CIN1
36.2%
HSIL/CIN2-3
  • Proportional-odds check: violated (P=0.024) → multinomial model chosen to separate LSIL vs HSIL risk.
  • Univariate screen: age, gravidity, age at first sex, partners, menopausal status, HPV, TCT and methylation all P<0.05.
  • Model fit: LR χ²=145.916; VIF <5 confirms no collinearity among markers.
方法要点：采用无序多项 Logistic 回归分析 LSIL 与 HSIL 的独立危险因素；甲基化阳性率从炎症（3.0%/3.6%）向 HSIL（30.4%/37.2%）陡升。
核心结论：JAM3 甲基化（OR 8.215）与 PAX1 甲基化（OR 4.145）为 HSIL 最强的独立危险因素，优于非NILM TCT（OR 2.399）。

3Independent Risk Factors for HSIL (vs Inflammation)

JAM3 methylation +
8.215
OR 8.22
Very-high-risk HPV 16/18
6.801
OR 6.80
PAX1 methylation +
4.145
OR 4.15
Non-NILM TCT
2.399
OR 2.40
  • JAM3 methylation strongest: OR 8.215 (95% CI 2.907–23.213, P<0.001) for HSIL — the top independent marker.
  • PAX1 adds value: OR 4.145 independently of HPV type and cytology — molecular layer beyond conventional tests.
  • HPV16/18: OR 6.801 remains a major driver; TCT (OR 2.399) contributes but weaker.

4Methylation Positivity Gradient

PAX1 · Inflammation
3.0%
3.0%
PAX1 · HSIL
30.4%
30.4%
JAM3 · Inflammation
3.6%
3.6%
JAM3 · HSIL
37.2%
37.2%
Positivity rises steeply from inflammation to HSIL — a clear dose–response supporting clinical use.

5Risk Stratification & Significance

  • Independent association: HR-HPV, non-NILM TCT and PAX1/JAM3 methylation each independently link to high-grade lesions.
  • Objective add-on: methylation quantifies host transformation — strengthens risk stratification beyond HPV/TCT alone.
  • Decision support: positive methylation flags high-risk women for colposcopy despite negative cytology.
  • Next steps: larger prospective studies to validate utility and cost-effectiveness in routine screening.
30.4%
PAX1+ in HSIL
37.2%
JAM3+ in HSIL
3–4%
in inflammation
  • Low-grade signal: methylation not significant for LSIL — viral/cytological drivers dominate early lesions.
  • High-grade signal: methylation becomes a decisive independent factor at the HSIL stage.
Methylation assay: PCR–fluorescence probe; positive = ΔCt PAX1 ≤6.6 or JAM3 ≤10.0; CV <5% intra, <10% inter.
Clinical Significance