A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

Author:

Herzog Chiara12ORCID,Marín Fátima34ORCID,Jones Allison5,Evans Iona5,Reisel Daniel5,Redl Elisa12,Schreiberhuber Lena12ORCID,Paytubi Sonia6ORCID,Pelegrina Beatriz6ORCID,Carmona Álvaro6ORCID,Peremiquel-Trillas Paula6ORCID,Frias-Gomez Jon6,Pineda Marta34ORCID,Brunet Joan347ORCID,Ponce Jordi48ORCID,Matias-Guiu Xavier49,de Sanjosé Silvia10,Alemany Laia611,Olaitan Adeola12,Wong Michael12ORCID,Jurkovic Davor12,Crosbie Emma J.1314ORCID,Rosenthal Adam N.5,Bjørge Line1516ORCID,Zikan Michal17ORCID,Dostalek Lukas18ORCID,Cibula David18ORCID,Sundström Karin19ORCID,Dillner Joakim19ORCID,Costas Laura611,Widschwendter Martin12520ORCID

Affiliation:

1. European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria

2. Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria

3. Hereditary Cancer Group, Catalan Institute of Oncology, IDIBELL, ONCOBELL Program, L'Hospitalet, Barcelona, Spain

4. Consortium for Biomedical Research in Cancer—CIBERONC, Carlos III Institute of Health, Madrid, Spain

5. Department of Women's Cancer, University College London, London, United Kingdom

6. Cancer Epidemiology Research Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain

7. Hereditary Cancer Group, Catalan Institute of Oncology, IDIBGI, Girona, Spain

8. Department of Gynecology, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain

9. Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain

10. ISGlobal, Barcelona, Spain

11. Consortium for Biomedical Research in Epidemiology and Public Health—CIBERESP, Carlos III Institute of Health, Madrid, Spain

12. University College Hospital, London, United Kingdom

13. Department of Obstetrics and Gynaecology, Manchester Academic Health Science Center, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom

14. Gynaecological Oncology Research Group, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom

15. Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway

16. Department of Clinical Science, Center for Cancer Biomarkers CCBIO, University of Bergen, Bergen, Norway

17. Department of Gynecology and Obstetrics, Charles University in Prague, First Faculty of Medicine and Bulovka University Hospital, Czech Republic

18. Department of Obstetrics and Gynecology, First Faculty of Medicine, Gynaecologic Oncology Center, Charles University in Prague, General University Hospital in Prague, Prague, Czech Republic

19. Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

20. Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden

Abstract

PURPOSE Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS We describe the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker 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 EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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