A step toward detecting endometrial cancer earlier

By Mayo Clinic staff

Endometrial cancer, also called uterine cancer, begins as a growth of abnormal cells in the uterus. If this type of cancer is found early, surgically removing the uterus often cures it. There is no screening test for endometrial cancer right now.

The results of a Mayo Clinic-led study published in Gynecologic Oncology in 2023, however, may help healthcare professionals detect endometrial cancer earlier by testing vaginal fluid for the presence of cancer-specific methylated DNA markers.

"We discovered methylated DNA markers that could be used to identify endometrial cancer through vaginal fluid collected with a tampon," says Jamie Bakkum-Gamez, M.D., a Mayo Clinic gynecologic oncologist. "This could lead to earlier detection and better survival."

Methylation is a mechanism cells use to control the expression of genes. When a certain area of a gene’s DNA is methylated, the gene is turned off or silenced. This indicates that a gene is a tumor suppressor. The silencing of tumor suppressor genes is often an early step in cancer development and can indicate cancer.

This research could lead to a screening test for endometrial cancer — one that could be performed in the privacy and comfort of your own home.

Another benefit could be providing an alternative to endometrial biopsy. During this procedure, a healthcare professional inserts a speculum into the vagina and then passes a long, straw-like instrument through the cervix to obtain tissue from the lining of the uterus.

"Though (biopsy is) the gold standard for obtaining a cancer diagnosis, this technique can be painful for the patient,” says Dr. Bakkum-Gamez.

How the study was designed

In 2004, the journal Cancer Epidemiology, Biomarkers and Prevention published an Austrian study that used tampons to distinguish endometrial cancer from noncancerous tissue by identifying methylated genes. Dr. Bakkum-Gamez and her colleagues set out to replicate this 2004 study. They conducted a study at Mayo Clinic that identified certain genes methylated in endometrial cancer and published their promising findings in Gynecologic Oncology in 2015.

In their 2023 study, Dr. Bakkum-Gamez and her team wanted to identify additional genes methylated in endometrial cancer.

In the study's discovery phase, researchers identified methylated DNA markers using samples of DNA from frozen endometrial cancer tissue and noncancerous tissue taken from the endometrium (lining of the uterus), cervix and vagina. They then validated these markers in a separate set of endometrial cancer and noncancerous tissues.

Next, the researchers examined vaginal fluid collected by study participants using an over-the-counter, unscented tampon. The study team analyzed the vaginal fluid DNA and identified methylated DNA markers associated with endometrial cancer.

All women participating in the study had experienced abnormal uterine bleeding at age 45 or older or postmenopausal bleeding or had been diagnosed with endometrial cancer through biopsy at any age. Abnormal uterine bleeding or postmenopausal bleeding is the most common symptom of endometrial cancer. While only 5% to 10% of people who experience this symptom will have endometrial cancer, all should be evaluated to rule out or confirm the diagnosis.

Researchers developed a panel of 28 methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue with 96% specificity (proportion of samples correctly identified as positive) and 76% sensitivity (proportion of samples correctly identified as negative) in vaginal fluid.

The study team also developed an abbreviated panel of three methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue with 96% specificity and 82% sensitivity in vaginal fluid.

Dr. Bakkum-Gamez and her colleagues also demonstrated that DNA methylation increases as cells change from the precursor to endometrial cancer, called endometrial hyperplasia, to endometrial cancer. This could allow using methylated DNA markers to detect precancerous lesions so healthcare professionals can treat them and prevent endometrial cancer from developing.

Next steps in endometrial cancer and other gynecological cancer early-detection research

Researchers are still finalizing the minimum length of time women would need to wear the tampon for fluid collection as part of an endometrial cancer screening test. In the study published in Gynecologic Oncology in 2023, the average time was 40 minutes.

Dr. Bakkum-Gamez says the ultimate cost of tampon-based testing will depend on how test development unfolds. "Our goal is a no-cost or an affordable out-of-pocket cost for women to use this at-home test," she says.

Though she calls these findings promising, Dr. Bakkum-Gamez says larger studies using this tampon-based fluid collection approach are needed. "We hope this test will be available to the public in a few years. And while this test is for women who are experiencing symptoms that may represent endometrial cancer, I hope a screening test collected via a similar approach will be available in the future for women who do not experience symptoms," she says.

The research team is looking into the early detection of other gynecological cancers using the tampon-based fluid collection. They are leading a pan-gynecologic cancer detection test clinical trial to test vaginal fluid for the presence of cancer-specific methylated DNA markers identified for endometrial cancer, ovarian cancer and cervical cancer, as well as high-risk HPV (human papillomavirus).

"Ideally, I would love to bundle testing together so we could pick up ovarian, cervical and other cancers all at the same time," says Dr. Bakkum-Gamez.

Funding

This work was supported by the V Foundation, the National Cancer Institute, the Mayo Clinic Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center.

Financial disclosures. John B. Kisiel, M.D., Jamie N. Bakkum-Gamez, M.D., Douglas W. Mahoney, and William R. Taylor are inventors of Mayo Clinic intellectual property that is licensed to Exact Sciences (Madison, Wisconsin) and may receive royalties, paid to Mayo Clinic. Seth W. Slettedahl, Xiaoming Cao, Patrick H. Foote, Kelli N. Burger, Calise K. Berger, Maria C. O'Connell, Karen A. Doering, Maureen A. Lemens, Ann L. VanOosten and Julie K. Staub are supported under a contract between Mayo Clinic and Exact Sciences. Mark E. Sherman, M.D., has received collaborative research funding supported by Exact Sciences.

Learn more

Learn more about endometrial cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect, an online community for patients and caregivers.

Also, read these articles:

• "Uterine cancer rates are increasing: What can you do to protect yourself?"
• "Your toolkit for reducing cervical cancer risk"
• "Harnessing the immune system to fight ovarian cancer"
• "New surgical method for ovarian cancer lights up lesions"
• "Mayo Clinic experts answer 4 questions about gynecologic cancer