Improved 'Patient-Friendly, Simple' Test to Screen for Endometrial Cancer

A noninvasive reliable test for patients with symptoms suggestive of endometrial cancer (EC) may enable rapid triage of women at greatest risk, and avoid invasive investigations in healthy women.

The current route of diagnosis for suspected EC is transvaginal ultrasound (TVUS) followed by hysteroscopy and endometrial biopsy. The low specificity of TVUS as an initial triage test, however, results in potentially high numbers of unnecessary invasive follow-up procedures.

As described in the Journal of Clinical Oncology, Martin Widschwendter, MD, of University College London, and colleagues developed a rapid triage method that can rule out cancer without the need for initial referral to a specialist.

The following Q&A discusses the details of the study. (The researchers did not respond to requests for comment, and the answers here are from the text of the report.)

What does the study add to the literature?

A simple test to triage women with improved, or at least equivalent, accuracy to current standards (TVUS) without the need for specialist referral is urgently needed. Ideally, such a test should also be applicable across different sample types, including self-collected samples.

Assessing DNA methylation in 1,288 cervicovaginal specimens, we developed and applied the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC) in several different settings.

The test is based on quantitative, methylation-specific polymerase chain reaction (PCR) targeting one region in the gene ZSCAN12 and two regions in GYPC. Our data indicate that the WID-qEC may be amenable for use in self-collected samples and could improve triage and earlier diagnosis by reducing the need for in-person consultations and invasive testing caused by low specificity of TVUS.

What were the main findings?

We evaluated the WID-qEC, a three-marker DNA methylation–based test, in clinically relevant diagnostic and predictive settings using various sample collection devices (cervical smear, vaginal swab, and self-collected samples). Applying prespecified thresholds across settings and collection modalities, our data indicate that the WID-qEC performs at least equally well, if not better, than other strategies currently in use to screen and triage women with EC -- importantly, ultrasound investigation.

In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, the test detected EC with sensitivities of 97.2%, 90.1%, and 100%, respectively, and specificities of 75.8%, 86.7%, and 89.1%, respectively. The WID-qEC identified 90.9% of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology.

Our data indicate that the WID-qEC could be suitable for use with a variety of collection devices. This, in combination with the high sensitivity and specificity of the test particularly in symptomatic settings, could make the WID-qEC test especially valuable in conditions where access to specialists or even any healthcare professional might be restricted -- for example, in a global pandemic, in non-urban settings, or in cases of lengthy referral times.

When might the test be warranted to triage and prioritize endometrial cancer patients?

Initial clinical implementation of the WID-qEC test in circumstances where TVUS is inconclusive, not available, or declined by the patient is warranted to triage and prioritize patients with the highest cancer risk for hysteroscopy and endometrial biopsy.

Given the potential benefits of earlier diagnosis of ECs for survival and reduced healthcare costs, future studies could also evaluate the test's potential for screening of asymptomatic women with increased risk -- for instance, women with obesity or Lynch syndrome, or women in the general population over age 50 who are participating in routine cervical screening.

What about the costs?

Pelvic ultrasound costs in the United States range from $220 to $3,200, with a national average cost of $575. As a relatively low-cost, PCR-based test (estimated costs below $200) with the potential for self-collection of samples, thus reducing the need for specialist referral, the WID-qEC offers several benefits compared with current clinical practice.

What's the next step for the research?

Future large-scale prospective studies will be required to further strengthen these data -- in particular, for covariates for which sample numbers in the current study were small, such as, for example, premenopausal status, non-white ethnicities.

Women who might benefit the most from the WID-qEC in the near future might be those who present with abnormal bleeding or other symptoms suggestive of ECs undergoing triage for malignancies -- in particular, those for whom currently available tests (ultrasound) are less reliable. For example, although the number of non-white women in our settings was low, the performance of the WID-qEC to detect EC was similar in white and non-white women. Others who may benefit are women at high risk of developing EC. The WID-qEC exhibited a high negative predictive value in all settings.

What's the bottom-line message?

The WID-qEC could represent a patient-friendly test for the screening and triage of women with symptoms suggestive of EC or those at risk of EC. Because of its suitability for use in self-collected samples, the WID-qEC may be a suitable tool for managing women with abnormal bleeding, particularly when access to specialist care is restricted.

Read the study here.