Cancers · 2025;17(18):3010 · Prospective Study · Hong Kong

CDO1/CELF4 Methylation (epiHERA®) for Endometrial Cancer Detection

Prospective Evaluation of Cervical Scrapings CDO1 and CELF4 Methylation (epiHERA®) Assay in Detection of Endometrial Cancer
675 women · cervical scrapings vs endometrial histology · accuracy 97.3% · Se 84.1% / Sp 98.8% · AUC 0.92 · Kappa 0.85
Lee HSJ, Wu S, Yeung SY, Cheung CW, Fung WYL, Kwok PKS, Yung KK, Wong TKS, Kanneganti A, Lau TS
Prince of Wales Hospital, The Chinese University of Hong Kong · Cancers 2025;17(18):3010 · doi:10.3390/cancers17183010
675
women tested
97.3%
accuracy
84.1%
sensitivity
0.92
AUC · epiHERA

1Background & Objective

  • Gap: no reliable screening test for endometrial cancer; invasive assessment is costly & fails in 11% postmenopausal.
  • Objective: validate epiHERA® (CDO1/CELF4 methylation of cervical scrapings) for EC detection & triage.

2Study Design & Cohort

629
outpatient sampling
46
hysterectomy
69
EC (10.2%)
689
recruited
14
excluded
218
Pap smear done
  • Setting: Prince of Wales Hospital, HK; prospective, Jan 2023 – Nov 2024.
  • Indications: abnormal uterine bleeding · imaging suspicion · hyperplasia · cancer.
  • Assay: CDO1 + CELF4 methylation on ThinPrep cervical scrapings (epiHERA®).
  • Reference: same-day endometrial histology (outpatient or hysterectomy).
  • Exclusions: 12 sampling failure + 2 invalid assay → 675 analyzed.
  • Follow-up: 3 women later EC + 1 cervical cancer at 1–4 months.
  • Statistics: accuracy/Se/Sp/PPV/NPV · ROC · Cohen's kappa.
0.92
AUC
0.85
Kappa
0.8%
FNR
  • Reuse: ThinPrep samples also used for cytology — no extra collection.
  • Limit: single-center; prospective but non-randomized.
Endometrial thickness
affects accuracy
Abnormal cytology
affects accuracy
Endometrial hyperplasia
affects accuracy
Sensitivity & NPV highest when endometrium thin; accuracy lower with hyperplasia.

3Performance Matrix

84.1%
Sensitivity
98.8%
Specificity
89.2%
PPV
98.2%
NPV
97.3%
Accuracy
0.85
Kappa
0.8%
FNR (outpatient)

4ROC — Combined Methylation

ROC curve of CDO1+CELF4 methylation for endometrial cancer
Fig. ROC — combined CDO1 + CELF4 methylation (AUC 0.92).
Sensitivity
84.1%
Specificity
98.8%
0.92
AUC (excellent)
0.85
Kappa
0.8%
FNR
  • Highly specific: 98.8% — few false referrals to invasive tests.
  • Low FNR: negative result safely defers endometrial assessment.
  • Kappa 0.85: near-perfect agreement with histology.
  • Balanced cut-off: AUC 0.92 — excellent discrimination.

5False Positives — Early Detection Signal

FP → hyperplasia
5 of 7
FP → CIN
2 of 7
later cancer (1–4 mo)
4 women
  • All 7 FP tied to genital-tract neoplasia — methylation precedes histology.
  • Triage value: fewer invasive tests, early-stage catch.
Clinical Significance