MILAN – Inex Innovate of Singapore plans to launch a PCR-based endometrial cancer detection test this summer, following interim results from a clinical study with researchers at the Chinese University of Hong Kong that were presented here at the Association of Molecular Pathology 2023 Europe Congress this week.
Endometrial cancer is the most common gynecological cancer, with more than 400,000 newly diagnosed cases each year around the world and almost 100,000 annual deaths. Common symptoms include abnormal vaginal bleeding after menopause, pelvic pain, and an enlarged uterus.
Existing methods to diagnose the cancer, such as endometrial biopsy, hysteroscopy, and transvaginal ultrasound, all have shortcomings, according to Vinod Benjamin, a researcher at Inex who gave a talk about the company's new test, called epiHera, on Monday. For example, they require the expertise of a pathologist or clinician, are painful and invasive, have long turnaround times, or can miss diagnoses.
To address this, Inex set out to develop a minimally invasive test that relies on methylated biomarkers. It is based on a study, published by a team in Taiwan in 2016, that showed hypermethylation of three genes in cervical scrapes from endometrial cancer patients. For its test, Inex decided to focus on two of these genes, CDO1 and CELF4.
EpiHera starts with the collection of a cervical swab, the same type of sample that is used in cervical cancer screening. Genomic DNA is then extracted and undergoes bisulfite conversion, where unmethylated cytosine is converted to uracil but methylated cytosine remains intact. This is followed by real-time PCR to detect hypermethylated CDO1 and CELF4. The test takes about six hours to perform with another day for the sample collection, Benjamin said.
For an initial proof-of-concept study, Inex researchers analyzed FFPE samples from 50 patients diagnosed with different types of endometrial cancer, of which the test was able to pick up almost 40.
They then went on to initiate a clinical study in collaboration with researchers in the department of obstetrics and gynecology at CUHK. The study plans to recruit about 700 adult patients and is expected to wrap up early next year. So far, the team has collected samples from about 250 women, and Benjamin presented interim results from 131 participants.
The project includes women with one or more risk factors for endometrial cancer, such as abnormal uterine bleeding. Women with a history of the cancer, pregnancy, ongoing menstruation, and certain vaginal treatments are excluded. For each participant, endometrial swabs are collected along with endometrial samples for diagnosis by a pathologist.
Of the 131 women, 10 received a positive pathology diagnosis. Of those, epiHera called nine as positive, suggesting 90 percent sensitivity. The one sample the test did not call came from a woman with a high body mass index, Benjamin said, which may explain the result. All 121 women who received a negative result by pathology were also called as negative by the epiHera test, translating to 100 percent specificity.
Benjamin said epiHera may be used clinically in three different scenarios: early on as a supplement to transvaginal ultrasound to prevent missed diagnoses, to distinguish between benign and malignant endometrial intraepithelial neoplasia, and to assess and monitor endometrial cancer patients following surgery.
The test offers several advantages, he said, including its short turnaround time of two days, compared to two weeks for endometrial biopsy procedures. It is also more comfortable for patients, sample collection is easy, and it is more cost-effective than biopsies, which he said can cost about $5,000 in Singapore. He did not mention pricing information for the EpiHera test. It is also easier to implement by a lab than a sequencing-based test, he said, and can be scaled to 94 samples per PCR run. Thus, it represents "the perfect opportunity to use the same PCR machines that have been gathering dust after COVID," he said.
Anansa Ahmed, head of product development at Inex, told GenomeWeb that the company plans to launch epiHera as a lab-developed test in August. Longer term, she said, the firm wants to run the test concurrently with HPV testing, as it can be performed using the same sample type.