Detect

Early detection of cancers can help to significantly improve prognosis of patients and reduce mortality. This is particularly pronounced for cancers that, despite advances in diagnostic procedures, are still only detected late.

Ovarian cancer is often detected at advanced stages and as a result has a five-year survival rate of less than 40%.
Womb cancer is the fourth most common cancer in women and its prevalence is increasing. No screening exists for endometrial cancer and the lead symptom is abnormal uterine bleeding. Many women present with abnormal uterine bleeding, but most do not have cancer. Current imaging methods for detecting cancer in women with symptoms are suboptimal.
Cervical cancer screening is routine in many countries and saves lives. Nevertheless, current strategies for triaging women at risk following an HPV test could be improved.

Our work focuses on the early detection of all of these cancers.

WID®-qEC – womb cancer detection test

Abnormal uterine bleeding is a symptom of endometrial (womb) cancer, but most women with abnormal bleeding do not have womb cancer.

Simpler and more accurate methods to detect cancer in women with abnormal bleeding are urgently needed. Our new molecular WID®-qEC test detects endometrial cancer quickly and with high accuracy using a cervical smears or a vagina swab. The test offers many advantages over currently used methods of early detection, such as ultrasound. In the future, with this easy-to-perform test, many women with suspected endometrial cancer could be spared very stressful hysteroscopies and biopsies.

The test has also been assessed in a prospective, observational cohort study in London. In 400 women aged 45 and over who visited a specialist clinic in London because of abnormal bleeding, standard procedure for uterine cancer diagnosis included a series of imaging procedures (mainly ultrasound) followed, if necessary, by diagnostic surgery (hysteroscopy and curettage). Both ultrasound and the new WID^®-qEC test correctly detected the same number of uterine cancer cases (91 %). Compared to the standard procedure (ultrasound), the WID^®-qEC test would have rendered 90 % of the surgical diagnostic procedures unnecessary.

The WID^®-qEC test detected 100% of endometrial cancers with a high specificity in a prospective cohort study in 106 black women in Ghana. Ultrasound detected 67% of these cancers

The high sensitivity and specificity of the WID^®-qEC irrespective of sample collection device and medium, sample collector and precise sampling site.

Evans, Reisel, Jones, Bajrami et al. Performance of the WID-qEC test versus sonography to detect uterine cancers in women with abnormal uterine bleeding (EPI-SURE): a prospective, consecutive observational cohort study in the UK. Lancet Oncology. November 2023 DOI: 10.1016/S1470-2045(23)00466-7

Ken-Amoah S, Redl E, Domson BKS, Barrett JE, Schreiberhuber L, Herzog C, Arora R, Jones A, Evans I, Reisel D, Lamptey-Mills E, Nachinab VB, Pepera T, Olaitan A, Obiri-Yeboah D, Akakpo PK, Widschwendter M. Performance of the WID-qEC test to detect uterine cancers in black women with abnormal uterine bleeding: A prospective observational cohort study in Ghana. Int J Cancer. 2025 Mar 1;156(5):1055-1064. doi: 10.1002/ijc.35260

Illah O, Scott M, Redl E, Barrett JE, Schreiberhuber L, Herzog C, Vavourakis CD, Jones A, Evans I, Reisel D, Chandrasekaran D, Doufekas K, Graham R, Kotsopoulos IC, MacDonald N, Arora R, Olaitan A, Rosenthal A, Widschwendter M. High performance of the DNA methylation-based WID-qEC test for detecting uterine cancers independent of sampling modalities. Int J Cancer. 2024 Sep 1;155(5):800-806. doi: 10.1002/ijc.35000.

Herzog et al. A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets. Journal of Clinical Oncology 2022; 40(33):3828-3838. DOI: 10.1200/JCO.22.00266

Schreiberhuber et al. The WID™-qEC test – performance in a hospital-based cohort and feasibility to detect endometrial and cervical cancers. International Journal of Cancer. 2023; 152(6):1269-1274. doi: 10.1002/ijc.34275.

WID®-qCIN – cervical (pre)cancer detection test

In many countries, screening programmes for cervical (pre)cancer detection use primary human papilloma virus (HPV) testing followed by cytology for those found to be HPV positive.

Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30.

We have developed and validated an automatable three-marker PCR-based triage test that is highly sensitive and specific and predicts progression to CIN3+ in HPV+ patients. The EUTOPS team is currently validating the markers in samples from a large population-based cervical cancer screening cohort.

Herzog et al. DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test. Clin Epigenetics 14, 150 (2022). doi: 10.1186/s13148-022-01353-0.

EpiFemCare – Ovarian cancer detection

The EpiFemCare project was a European Commission funded programme running from November 2012 to April 2016 with the aim of identifying more sensitive and specific blood-based bioassays for the detection of ovarian and breast cancer. We employed the epigenome as a stable target molecule reflective of the disease. Prof Martin Widschwendter was the Coordinator and Principal Investigator of the EpiFemCare project and led an international consortium comprising clinicians, academics, and small- to medium enterprises (SMEs). By assessing methylation in prospectively collected samples, we were able to develop a markers for early blood-based detection of ovarian cancer.

In 2023, we published new data evaluating the cell-free DNA methylation (cfDNAme) markers in new diganostic and early detection settings. Our results show the test effectively distinguished benign pelvic conditions and ovarian cancers, and combination of cfDNAme with single CA125 measurement improved sensitivity beyond that of either marker alone. Furthermore, the cfDNAme test, called the WID-cfOC score, identified 33.3% of high-risk (grade 2 or 3) ovarian cancers up to a year before diagnosis.

Our data suggest that women with a positive score in either diagnostic modality, particularly double-positive individuals, could be referred for a PET-CT scan to rule out a positive result due to a different cancer, and could undergo surgery even in the absence of a visible ovarian tumour on imaging given the high specificity of cfDNAme.

Key publications

Widschwendter M,et al. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer. Genome Med. (2017); 9(1):116. doi: 10.1186/s13073-017-0500-7.

Herzog C, et al. Plasma cell-free DNA methylation analysis for ovarian cancer detection: Analysis of samples from a case-control study and an ovarian cancer screening trial. Int J Cancer. (2023); 1-13. doi: 10.1002/ijc.34757.

This project received funding from the European Union’s Framework Programme 7 research and innovation programme under grant agreement No 305438.

Principle of the WID®-qEC test

The WID®-qEC test is a simple, epigenetic test that detects womb cancer.

A doctor or healthcare professional takes a sample from the vagina. The sample is similar to the one taken for cervical cancer screening (“PAP smear”).

At the lab, epigenetic markers in the genes GYPC and ZSCAN12 are evaluated using a simple PCR technology, which is routinely implemented in many clinical settings including COVID-19 testing. The results only take a few days to process.