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A simple, non-invasive, and reliable epigenetic test can screen and rapidly triage women with symptoms suggestive of endometrial cancer, researchers reported.

As Martin Widschwendter, MD, of the European Translational Oncology Prevention and Screening Institute in Innsbruck, Austria, and colleagues noted in the , tests for suspected endometrial cancer are invasive, expensive, and require a specialist. A rapid triage modality that could rule out malignancies without the need for initial specialist referral could improve patient care and reduce time to diagnosis. The team aimed to develop a noninvasive endometrial cancer screening and triage test.

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 about screening for endometrial cancer?

A simple test to triage women with improved, or at least equivalent, accuracy to the current standard of transvaginal ultrasound (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. We developed and applied WID-qEC, the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer, 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 the low specificity of TVUS.

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 endometrial cancer -- most especially ultrasound investigation.

What were the study highlights?

Assessing DNA methylation in 1,288 cervicovaginal specimens, the WID-qEC identified 100% of endometrial cancers within a cohort of women presenting with postmenopausal bleeding at 89% specificity. Moreover, the test could also be performed on self-collected samples and resulted in higher accuracy than ultrasound and somatic mutation analysis in our setting.

In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, the test detected endometrial cancers 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 endometrial cancer 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, global pandemic, nonurban settings, or in case of lengthy referral times.

Are their particular groups of women who would benefit the most from this test?

Women who might benefit most from the WID-qEC in the near future might be women presenting with abnormal bleeding or other symptoms suggestive of endometrial cancer undergoing triage for malignancies -- in particular, those where 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 endometrial cancer was similar in white and non-white women.

Also, women at high risk of developing endometrial cancer may benefit from the test. The WID-qEC exhibited a high negative predictive value (NPV) in all settings.

How does the cost compare?

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 are the next steps for research?

Future prospective studies comparing TVUS and the WID-qEC side-by-side will guide clinical application of this methylation-based test.

Large-scale prospective studies will be required to further strengthen our data, in particular for covariates for which sample numbers in the current study were small -- for example, premenopausal status and non-white ethnicities. Diagnostic accuracy including positive predictive value and NPV of the WID-qEC should ultimately be evaluated in large-scale prospective clinical studies in each target population.

Given the potential benefits of earlier diagnosis of endometrial cancers 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 who are more than 50 years old who are participating in routine cervical screening.

What is the main take-home message for practicing oncologists?

The WID-qEC could represent a patient-friendly test for the screening and triage of women with symptoms suggestive of endometrial cancer or those at risk of endometrial cancer. 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.