Diagnostics · 2026;16(2):174 · Prospective Validation · China

Cervical Cell CDO1/CELF4 Methylation for Endometrial Cancer

Clinical Validation of DNA Methylation Detection in Cervical Exfoliated Cells for Endometrial Cancer in Women with Suspected Lesions
2,164 suspected-lesion women · EC Se 93.94% / Sp 96.7% · NPV 99.90% · EIN Se 83.87% / NPV 99.76% · TVS combination further improves
Yu Y, Su T, Zhang H, Li Q, Cong Q, Sui L, Chen L
Obstetrics & Gynecology Hospital, Fudan University · Diagnostics 2026;16(2):174 · ChiCTR2200055991
2,164
suspected lesions
93.9%
EC sensitivity
96.7%
EC specificity
99.90%
NPV · EC

1Background & Objective

  • Gap: no globally recommended non-invasive EC detection; TVS limited (specificity in AUB, sensitivity in obesity).
  • Objective: clinically validate CDO1m/CELF4m on exfoliated cervical cells, alone and with TVS.

2Study Design & Cohort

33
EC · 51.7y
31
EIN · 49.5y
2,100
non-lesion · 44.7y
  • Setting: Fudan OB/GYN Hospital hysteroscopy center; prospective, Jul 2023 – May 2024.
  • Sample: preoperative exfoliated cervical cells → dual-gene methylation (CDO1m/CELF4m).
  • Reference: hysteroscopic histopathology = gold standard.
  • Inclusion: ≥1 EC risk factor (endocrine, obesity, HTN, diabetes, etc.) + consent.
  • Exclusion: prior EC surgery · recent radio/chemo · CIN2+ · invalid samples.
93.9%
EC Se · 95%CI 79.8–99.3
96.7%
EC Sp · 95%CI 95.9–97.5
99.9%
EC NPV · 95%CI 99.6–100
51.7y
mean age · EC
49.5y
mean age · EIN
44.7y
mean age · other
EC prevalence
1.5%
EIN prevalence
1.4%
non-lesion
97.1%
  • Dual-gene readout: positive if either CDO1m or CELF4m above threshold.
  • Consistency: performance in line with prior CDO1/CELF4 cervical-cell studies.
  • Age gradient: EC > EIN > non-lesion (P<0.001).
  • Risk factors: endocrine disorder · obesity · hypertension · diabetes · infertility · genetics.
  • Interpretation: methylation(+) → high-risk triage; (−) → EC practically excluded (NPV 99.9%).
  • Prevalence: EC 1.5% · EIN 1.4% — explains low PPV but high NPV design.
  • Limits: single-center; PPV moderate in low-prevalence setting.
Registered ChiCTR2200055991 (Jan 30, 2023) · Ethics No. 2023-42.

3EC Detection — Methylation

93.9%
Sensitivity
96.7%
Specificity
31.0%
PPV
99.90%
NPV
  • High NPV: negative result virtually rules out EC — safe deferral of hysteroscopy.
  • Low PPV: reflects low EC prevalence (1.5%) in suspected-lesion cohort.

4EIN Detection — Methylation

83.9%
Sensitivity
98.0%
Specificity
37.7%
PPV
99.76%
NPV
  • Precancer detected: EIN (atypical hyperplasia) caught at 83.9% sensitivity.
  • Strong exclusion: NPV 99.76% — rules out precancer in practice.

5TVS Combination & Triage Value

EC Se · methylation
93.9%
EC Se · + TVS
improved ↑
EIN NPV · methylation
99.76%
TVS alone
lower Se/Sp
EC
Se 93.9% · Sp 96.7%
EIN
Se 83.9% · Sp 98.0%
NPV >99.7%
both endpoints
  • Combination: methylation + TVS raises sensitivity & NPV for both EC and EIN.
  • Workflow: positive methylation → hysteroscopy; negative → monitor & re-test.
  • Who benefits: women with AUB, thick endometrium, or obesity — avoid unnecessary invasive tests.
  • Practical: cervical cell collection is simple, painless & outpatient-based.
  • Follow-up: methylation(−) women re-test at 6–12 months; (+) proceed to hysteroscopy.
  • Direction: single-center validation → larger multi-center trials.
Triage complements — not replaces — hysteroscopy for treatment decisions.
Clinical Significance