Available from February 2025 within a clinical trial framework, the Endotest saliva test, developed by Ziwig, promises to transform screening for endometriosis. Clinicians and researchers continue to debate whether it can deliver on that promise.

The diagnosis of endometriosis remains lengthy and complex, with an average diagnostic delay of approximately 7 years. A reliable noninvasive test could substantially shorten the delay and spare women from invasive diagnostic procedures.

At the Paris Women’s Health Congress 2025, several sessions focused on this topic, although its relevance continues to be debated within the scientific community. Here is a review of the most recent data from the literature and the national trial now under way.

Validation Results

During a symposium, Ziwig presented findings from a prospective, multicenter validation of the ENDOmiRNA study aimed at assessing the diagnostic accuracy, validating the biological reproducibility, and evaluating the clinical utility of a salivary miRNA signature of endometriosis, published in The New England Journal of Medicine Evidence.

The results of the ENDOmiRNA study suggest that noninvasive Endotest could replace diagnostic laparoscopy for the diagnosis of endometriosis.

Conducted in 17 centers across France, the study showed that Endotest was associated with high sensitivity and specificity (97.3% and 94.1%, respectively), supporting the diagnostic performance of this salivary miRNA signature.

The study included 971 patients aged 18-43 years with signs and symptoms suggestive of endometriosis. Diagnosis was established using imaging, laparoscopy, or both. The overall prevalence of endometriosis in the cohort was 77%. All patients in whom endometriosis was not detected were classified as controls and underwent laparoscopy. Assessment of endometriosis status on the basis of the salivary miRNA signature was performed without knowledge of the diagnosis established by imaging, laparoscopy, or histology.

The test showed a particular value in the so-called discordant patients who had symptoms suggestive of endometriosis but negative or equivocal imaging results.

Data analysis showed that the salivary miRNA signature achieved an overall accuracy of 96.6%, defined as the probability of correct classification of positive and negative results, with a sensitivity of 97.3%, specificity of 94.1%, positive predictive value of 98.2%, negative predictive value of 91.3%, positive likelihood ratio of 16.6, and negative likelihood ratio of 0.03.

Among patients whose diagnosis was confirmed surgically, the rates of misclassification, underestimation, and overestimation were 4.6%, 2.4%, and 2.2%, respectively, for the salivary miRNA signature compared with 27.2%, 15.1%, and 12.2%, respectively, for imaging using transvaginal ultrasound, MRI, or both.

Test performance was not influenced by geographic or temporal factors, including the enrolling center, shipping time, or RNA sequencing delay, or by patient characteristics, such as age, presence or absence of endometriosis, disease stage, or use of hormonal or analgesic treatment.

Replacing Laparoscopy

In clinical practice, diagnostic laparoscopy is typically performed in patients with suggestive symptoms and negative or equivocal imaging results. This approach is costly, requires general anesthesia, and carries an estimated 2% risk for injury to adjacent organs, a risk for major vascular injury, and a mortality rate of about 1 in 10,000.

François Golfier, MD, PhD, is a university professor and hospital practitioner at Université Claude Bernard Lyon 1 in Villeurbanne, France. He heads the Department of Gynecological and Oncological Surgery-Obstetrics at Hôpital Lyon Sud, part of the Centre Hospitalier Universitaire de Lyon, Lyon, France, and is a leading expert in endometriosis.

He discussed the results of the study and suggested that the noninvasive Endotest could replace diagnostic laparoscopy in selected patients at congress.

“A study by Nisenblat and colleagues published in 2016 indicated that to replace laparoscopy, a test would require sensitivity of at least 0.94 and specificity of at least 0.79,” he said. “The sensitivity and specificity observed in ENDOmiRNA are well above those thresholds.”

These findings should help clarify how saliva tests may influence management decisions for patients with disabling symptoms suggestive of endometriosis whose MRI does not reveal lesions.

Endobest Trial

Although the ENDOmiRNA study results addressed diagnostic performance, its clinical utility still needs to be demonstrated. This was the aim of the national Endobest study, launched in February 2025.

The trial plans to include 2500 patients, with a total of 25,000 women granted free access to the saliva test under the innovation coverage program approved by the Haute Autorité de Santé. The test cost of €839 is covered by the national health insurance system. To date, more than 100 endometriosis centers have been established in France.

The study will assess how the saliva test modifies management decisions in patients with disabling symptoms suggestive of endometriosis and negative MRI results. The results are also expected to define the test’s position within the care pathway and inform future access and reimbursement.

Prescriptions are intended for patients with normal or equivocal imaging findings but highly suggestive and disabling symptoms. The inclusion criteria were age 18-43 years and chronic, severe pelvic pain suggestive of endometriosis, with a visual analog scale score greater than 8 despite negative or uncertain ultrasound or MRI findings.

The study had two primary endpoints. The first was the reduction in planned and performed laparoscopies based on test results among women for whom laparoscopy had previously been decided during a multidisciplinary case review. The second is the change in management following the test results in women without a prior indication for laparoscopy.

The initial results are expected to be achieved by mid-2026.

Ongoing Debate

However, some experts remain cautious regarding the usefulness of this test.

During the discussion session, Arnaud Fauconnier, MD, PhD, professor and head of the Department of Gynecology, Obstetrics and Reproductive Medicine at CHI Poissy-Saint-Germain-en-Laye, France, questioned the value of treating lesions that were not visible on imaging. “We are dealing with lesions that are superficial and limited. Do minimally visible lesions respond to surgery? We showed in a study that they do not,” he said.

In response, Golfier emphasized patient expectations while urging caution. “Women want to know whether or not they have endometriosis,” he said, adding, “We are certainly not saying that a positive test means surgery is required. Because pain is multifactorial, claiming that a positive test means women are in pain only because of endometriosis would be absolute heresy.”

Endometriosis is the only possible cause of menstrual pain. Management includes patient education focused on menstruation, targeted analgesics and nonsteroidal anti-inflammatory drugs, and adjustment of hormonal contraceptive prescriptions to reduce the frequency and volume of menstruation.

Networks in France

Since the launch of the National Endometriosis Strategy in February 2022, regional health agencies in each region of France have established dedicated endometriosis care networks. These networks aim to structure and coordinate care pathways, raise awareness, promote personalized management, and contribute to the research and prevention of endometriosis.

During the congress, Pierre Collinet, MD, PhD, gynecological surgeon specializing in endometriosis and minimally invasive surgery at Hôpital Privé Le Bois, Ramsay Lille Métropole in Lille, France, and General Secretary for Surgery at the National College of French Gynecologists and Obstetricians, a professional body for obstetricians and gynecologists in France, said, “To harmonize how each regional network operates, a national club of regional endometriosis networks has been created.”

Golfier reported being a member of the Ziwig scientific advisory board.

Collinet reported having relationships with Nordic Pharma, Olympus, and Ethicon related to the organization and delivery of surgical training sessions; having relationships with Ipsen and Bayer, relating to financial support and workshop organization; and serving in a consultancy role with Exeltis.

Fauconnier reported having relationships with Effik, Helfie AI, Selas Pointgyn, and Innotech International.

This story was translated from Medscape’s French edition.