Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.
Yuxuan WangLu LiChristopher B DouvilleJoshua David CohenTing-Tai YenIsaac KindeKarin SundfeltSusanne K KjaerRalph H HrubanIe-Ming ShihTian-Li WangRobert J KurmanSimeon SpringerJanine PtakMaria PopoliJoy SchaeferNatalie SillmanLisa DobbynEdward J TannerAna AngaritaMaria LyckeKirsten Marie JochumsenBahman AfsariLudmila V DanilovaDouglas A LevineKris JardonXing ZengJocelyne ArseneauLili FuLuis A DiazRachel KarchinCristian TomasettiKenneth W KinzlerBert VogelsteinAmanda N FaderLucy GilbertNickolas PapadopoulosPublished in: Science translational medicine (2019)
We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease. In contrast, only 1.4% of 714 women without cancer had positive Pap brush samples (specificity, ~99%). Next, we showed that intrauterine sampling with a Tao brush increased the detection of malignancy over endocervical sampling with a Pap brush: 93% of 123 (95% CI, 87 to 97%) patients with endometrial cancer and 45% of 51 (95% CI, 31 to 60%) patients with ovarian cancer were positive, whereas none of the samples from 125 women without cancer were positive (specificity, 100%). Finally, in 83 ovarian cancer patients in whom plasma was available, circulating tumor DNA was found in 43% of patients (95% CI, 33 to 55%). When plasma and Pap brush samples were both tested, the sensitivity for ovarian cancer increased to 63% (95% CI, 51 to 73%). These results demonstrate the potential of mutation-based diagnostics to detect gynecologic cancers at a stage when they are more likely to be curable.
Keyphrases
- endometrial cancer
- circulating tumor
- early stage
- cell free
- papillary thyroid
- loop mediated isothermal amplification
- circulating tumor cells
- polycystic ovary syndrome
- real time pcr
- label free
- childhood cancer
- high throughput
- end stage renal disease
- newly diagnosed
- ejection fraction
- squamous cell
- genome wide
- magnetic resonance
- metabolic syndrome
- chronic kidney disease
- magnetic resonance imaging
- type diabetes
- ionic liquid
- computed tomography
- clinical practice
- squamous cell carcinoma
- pregnancy outcomes
- skeletal muscle
- contrast enhanced