The DNA-based test showed 96.8% specificity in cervical samples and could help physicians determine which patients need further testing for endometrial cancer.

A peer-reviewed study published in Gynecologic Oncology Reports provides clinical and analytical validation for Gnosis’ EdenDx, a noninvasive laboratory-developed triage test designed to detect endometrial cancer.

In cervical cytology specimens collected in standard ThinPrep vials, the assay demonstrated 96.8% specificity. In endometrial biopsy tissue from US patients, it identified 85% of cancers with 90% specificity. The dual-biomarker molecular assay evaluates hypermethylation of CDO1 and CELF4, two genes linked to endometrial neoplasia.

Endometrial cancer remains the most prevalent gynecologic malignancy in the United States, with the American Cancer Society projecting 68,270 new cases and 14,450 deaths in 2026. Mortality increased 1.9% annually between 2015 and 2019, while incidence among Black women rose 2.4% annually, nearly five times the rate observed in White women. Despite rising numbers, no population-wide screening program or noninvasive test cleared by the Food and Drug Administration currently exists.

Addressing Diagnostic Limitations in Triage

Current clinical pathways face significant diagnostic hurdles. In April 2026, the American College of Obstetricians and Gynecologists recommended tissue sampling alongside ultrasound for most patients experiencing postmenopausal bleeding. However, endometrial biopsy yields insufficient tissue in roughly 31% of procedures, and more than 90% of evaluated patients do not have endometrial cancer.

Standard front-line assessment modalities also exhibit variable accuracy: transvaginal ultrasound specificity ranges between 24% and 72%, and Pap cytology identifies only 25% to 45% of malignancies.

Unlike imaging tools that rely on endometrial thickness measurements subject to hormonal variation, EdenDx analyzes specific DNA methylation patterns. In the study, a positive test result raised the odds of cancer by more than 22-fold. Within cervical specimens, the test detected 72.2% of cancers overall, including 82% of grade 1 tumors and 81% of endometrioid adenocarcinomas.

“CDO1 and CELF4 methylation changes arise early in the development of endometrial cancer, in some cases before symptoms appear, and that is precisely what makes them so valuable diagnostically,” says Safedin Beqaj, PhD, laboratory director at Gnosis, in a release. “EdenDx detects those changes directly in a routine cervical specimen, without relying on how cells look under a microscope. For a disease whose evaluation has long relied on tissue sampling alone, that represents a genuine advance.”

Analytical Performance and Clinical Workflow

Because previous evaluations of CDO1 and CELF4 methylation focused primarily on Asian populations, Gnosis investigators evaluated the biomarkers across cohorts that included US patients. Cervical specimens sourced from Singapore and California demonstrated specificity aligning with the 86.6% to 98.8% range documented in earlier trials, while biopsy specimens from 40 US patients corroborated performance in domestic cohorts.

Analytical validation indicated stable performance under standard laboratory conditions:

  • The assay detected tumor DNA when malignant cells represented as little as 1.5% of a specimen.
  • Run-to-run variation remained below 10%.
  • Test accuracy was not altered by blood, semen, common vaginal infections, or over-the-counter vaginal products.
  • No false positives occurred in samples positive for human papillomavirus-related abnormal Pap smears, benign ovarian cysts, or metastatic ovarian cancer.

The assay operates as a CLIA laboratory-developed test requiring no specialized collection equipment beyond routine liquid-based cytology vials. The test is intended for symptomatic individuals, premenopausal patients for whom ultrasound is less reliable, and populations at elevated risk due to abnormal uterine bleeding, obesity, Lynch syndrome, chronic anovulation, or tamoxifen therapy. The assay is designed to support clinical triage decisions rather than replace diagnostic tissue biopsy.

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