Expert Discusses Role of Vaginal Microbes in Endometrial Cancer Detection

Marina R.S. Walther-António, PhD

A direct assessment of the uterine microbiome in patients with endometrial cancer has revealed a potential predictive role for vaginal microbes, according to the results of a novel study published in Genome Medicine.

The findings showed that the uterine microbiome of women with endometrial cancer is different from the uterine microbiome of women without endometrial cancer. Additionally, the microbes present in the vaginal environment of women with endometrial cancer are also different from the microbes present in the vaginal environment of women who do not have endometrial cancer.

“These findings provide important insights into the etiology or manifestation of the disease with broad implications for biomarker development in the early detection of, and screening for, endometrial cancer,” Marina R.S. Walther-António, PhD, assistant professor of Surgery, Mayo Clinic, and lead author of the study, said in a statement.

OncLive: Please discuss the rationale behind this study and some of the most significant findings.

In an interview with OncLive, Walther-António discussed the most significant findings from this study, the major challenges in this research, and the next steps following her findings.Walther-António: The original idea was just that there was nothing out there that was known about the endometrial microbiome. There were recently some publications about the microbes in the uterus through indirect methods, but in terms of direct access, this was the first look.

So, at Mayo Clinic, there was a thought that there could be a potential microbial environment that was implicated either in the manifestation or eventually the etiology of the disease. So we set out to do something like that, and it was a lot more challenging than we thought, because we had to collect samples in the operating room, and the physicians there collected them. The samples had to be collected under sterile conditions in pathology, which is not typically the way they perform their work. So we had to set up ways to make this workflow function without interfering with patient care, which was challenging.

I think it took about 2 years altogether to get this going in a streamlined fashion, but we got it. And it was worth it because what we found was that, in fact, there are some differential microbiome signatures between patients who were having a hysterectomy—meaning a removal of the uterus and sometimes Fallopian tubes and ovaries as well—the ones that had cancer had different signatures than the ones who had surgery for other benign conditions.

Not only did we find those differential signatures, but we could also see that signature in the vaginal environment. That was really interesting because there’s a possibility that we can do a vaginal swab in a patient and have an indication as to whether the patient has cancer or not.

How were the microbiomes different exactly?

What we’re trying to follow up that work with is actually a predictor marker, and for that, we’re using benign biopsies that patients have had in the past, and then these same patients developed cancer in a matter of months or years, so we’re trying to see if we can predict those patients who are at high risk for actually developing cancer and have developed it or not. That would be a predictor more toward early intervention or prevention, potentially in the future, if we do find some relation between the microbes and the disease itself that could be actionable. So that’s what we’re pursuing right now.We did what’s called a 16S rDNA analysis. It can be used to basically fingerprint the bacteria. I like to think of it in the same way we have fingerprints between different people, the 16s signatures are fairly unique to the species level, or at least the genus level, so it allows us to know what we’re working with in a very fine way without having to do endometrial cultures. Even if we don’t know exactly what they do, we know who they are. So that’s how we did the experiment: we looked for that signature, and we found that that signature in that bacterial community in endometrial cancer patients was different from the ones without cancer.

What were some of the biggest challenges in this study that you’d like to address in the next steps?

And then you can do several different assessments to refine that and see if there are markers, if there are particular bacteria that are associated with the manifestation of cancer. If not, then we can develop more direct assays to go after it rather than having to do the whole sequencing process, which is expensive and takes time.We have a challenge of a small cohort. It was a difficult study to put together. We’re limited by the numbers. Now we actually have almost 200 patients altogether that we’re in the process of analyzing. So we have extended that to validate the findings.

Another problem was, because we’re in Rochester, Minnesota, most of our patients were Caucasian, so our conclusions are limited to that population. That’s something we want to address, extending the study to minorities at other institutions—particularly because African-American women have a higher death rate due to the disease than Caucasian women. So we’re trying to see if these findings are valid for those other populations, which would be very important.

What do you ideally hope to see in the next 5 to 10 years in this treatment landscape?

We’re also limited by an age gap. The endometrial cancer population tends to be older than the population that has that surgery for benign reasons, so that’s something that we’re also now looking at in the larger cohort. Some of the differences could be due to age differences, and we have done a lot of stats on it, too, to make sure it wasn’t heavily impacted by the age difference, but we know that there’s always some effect, for sure.It seems that prevention is really the main priority for endometrial cancer. The mortality rates are increasing, and the estimation is that, by 2030, endometrial cancer will surpass colon cancer altogether in terms of incidence rate. Even though it is a cancer that is usually caught early—because women usually have abnormal bleeding that leads them to seek medical attention—it still requires surgery, and it’s a huge burden, obviously. So prevention would really be key, which is why we’re looking for predictors that can at least predict the development of the disease with high confidence so that something can be done to prevent it.

Walther-António MRS, Chen J, Multinu F, et al. Potential contribution of the uterine microbiome in the development of endometrial cancer [published online November 25, 2016]. Genome Medicine. doi:10.1186/s13073-016-0368-y.