Abstract
Purpose
Endometrial cancer incidence has been rising over the past ten years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, non-invasive, and reliable triage test for endometrial cancer to reduce the number of invasive diagnostic procedures and improve patient survival.
Patients and methods
We developed a test to screen and triage women with suspected endometrial cancer using 726 cervical smear samples from women with and without endometrial cancer, and validated the test in 562 cervico-vaginal samples utilizing three different collection methods (cervical smear – n=248, vaginal swab – n=63, self-collection – n=251) and four different settings (case/control – n=388; cohort of women presenting with post-menopausal bleeding – n=63; a cohort of high-risk women with Lynch syndrome – n=25; a nested case/control setting from a screening cohort and samples taken up to 3 years prior to endometrial cancer diagnosis – n=86).
Results
We describe the WIDTM-qEC test, a three-marker PCR-based test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected endometrial cancer with sensitivities of 97.2% (95% CI: 90.2-88.7%), 90.1% (83.6-94.6%), and 100% (63.1-100%), respectively, and specificities of 75.8% (63.6-85.5%), 86.7% (79.3-92.2%), and 89.1% (77.8-95.9%). The WIDTM-qEC identified 90.9% (95% CI 70.8-98.9%) of endometrial cancer cases in samples predating diagnosis up to one year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology.
Conclusion
The WIDTM-qEC is a non-invasive reliable test for triage of women with symptoms suggestive of uterine cancers. Due to the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.
Endometrial cancer incidence has been rising over the past ten years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, non-invasive, and reliable triage test for endometrial cancer to reduce the number of invasive diagnostic procedures and improve patient survival.
Patients and methods
We developed a test to screen and triage women with suspected endometrial cancer using 726 cervical smear samples from women with and without endometrial cancer, and validated the test in 562 cervico-vaginal samples utilizing three different collection methods (cervical smear – n=248, vaginal swab – n=63, self-collection – n=251) and four different settings (case/control – n=388; cohort of women presenting with post-menopausal bleeding – n=63; a cohort of high-risk women with Lynch syndrome – n=25; a nested case/control setting from a screening cohort and samples taken up to 3 years prior to endometrial cancer diagnosis – n=86).
Results
We describe the WIDTM-qEC test, a three-marker PCR-based test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected endometrial cancer with sensitivities of 97.2% (95% CI: 90.2-88.7%), 90.1% (83.6-94.6%), and 100% (63.1-100%), respectively, and specificities of 75.8% (63.6-85.5%), 86.7% (79.3-92.2%), and 89.1% (77.8-95.9%). The WIDTM-qEC identified 90.9% (95% CI 70.8-98.9%) of endometrial cancer cases in samples predating diagnosis up to one year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology.
Conclusion
The WIDTM-qEC is a non-invasive reliable test for triage of women with symptoms suggestive of uterine cancers. Due to the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.
| Original language | English |
|---|---|
| Journal | Journal of Clinical Oncology |
| Publication status | Accepted/In press - 1 Jul 2022 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
