Alicia Latham, MD, MS, Memorial Sloan Kettering Cancer Center, New York, New York, discusses results from a feasibility study which compared pap-derived ctDNA vs plasma-derived ctDNA among patients with either endometrial cancer undergoing surgery or Lynch syndrome undergoing risk-reducing hysterectomy and bilateral salpingo-oophorectomy. 

Study results demonstrated that pap-derived ctDNA resulted in higher ctDNA yield compared to plasma-derived ctDNA and was able to detect more tumor mutations thus making pap-derived ctDNA a promising tool for the detection of endometrial cancer. 

Dr Latham presented these results at the 2025 ASCO Annual Meeting in Chicago, Illinois. 

Transcript:

I’m Alicia Latham and here at ASCO this year I presented feasibility of pap-derived cell-free DNA (cfDNA) for early detection of sporadic and Lynch-associated endometrial cancer.  

The main point as to why we did this feasibility study is that currently we have no proven effective screening for endometrial cancer for women – and I think that that's a real disservice in 2025. Essentially, the idea behind this was because we know that MCED [multi-cancer early detection] testing, which is a big component of this meeting today, we know that some tumors don't shed DNA very well into the peripheral circulation. One of those is certainly endometrial cancer, so the idea and the hypothesis behind this is that if cell-free DNA is shed into plasma or blood then perhaps other body fluids that might be a little closer to the target tissue might have a better yield and in fact, that's what we found. 

We looked at 16 patients with known uterine cancer and collected both a plasma- or blood-based test as well as our pap-based assay and found that we had concentrations 5 times higher in the pap smear type sample compared to the plasma. Not just did we have higher yield, but we were able to detect tumor mutations in over 90% of our uterine cancer affected patients, of which 81% were early-stage disease. That's in comparison to only a quarter of them being detected in the blood. 

The point behind this is that we are trying to develop a new way to screen for cancers for which we currently don't have available screening. Right now, one of our target populations in the next phase of this work is using this in women at increased risk, so those with a genetic susceptibility to uterine cancer like Lynch syndrome for example. Right now, those women are recommended to undergo risk-reducing surgery prior to menopause because we don't have effective screening for this cancer. Because these women are at risk for uterine as well as ovarian cancer, they go through surgical menopause, and that is a major quality of life issue and a huge barrier as to why many women choose not to go that route and need and want screening.

The next phase is to continue to do a longitudinal collection using this as a potential screening test and expanding it hopefully into more of the general population.

Source: 

Latham A, Mueller J, Charalambous K, et al. Feasibility of Pap-derived ctDNA for detection of sporadic and Lynch-associated endometrial cancer. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 10503