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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers

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  • Yuxuan Wang
  • Lu Li
  • Christopher Douville
  • Joshua D Cohen
  • Ting-Tai Yen
  • Isaac Kinde
  • Karin Sundfelt
  • Susanne K Kjær
  • Ralph H Hruban
  • Ie-Ming Shih
  • Tian-Li Wang
  • Robert J Kurman
  • Simeon Springer
  • Janine Ptak
  • Maria Popoli
  • Joy Schaefer
  • Natalie Silliman
  • Lisa Dobbyn
  • Edward J Tanner
  • Ana Angarita
  • Maria Lycke
  • Kirsten Jochumsen
  • Bahman Afsari
  • Ludmila Danilova
  • Douglas A Levine
  • Kris Jardon
  • Xing Zeng
  • Jocelyne Arseneau
  • Lili Fu
  • Luis A Diaz
  • Rachel Karchin
  • Cristian Tomasetti
  • Kenneth W Kinzler
  • Bert Vogelstein
  • Amanda N Fader
  • Lucy Gilbert
  • Nickolas Papadopoulos
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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.

Original languageEnglish
JournalScience translational medicine
Volume10
Issue number433
Pages (from-to)eaap8793
ISSN1946-6234
DOIs
Publication statusPublished - 21 Mar 2018

ID: 56090600