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Sci Transl Med. 2018 Mar 21;10(433). pii: eaap8793. doi: 10.1126/scitranslmed.aap8793.

Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.

Author information

1
Ludwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
2
Division of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
5
PapGene Inc. Baltimore, MD 21211, USA.
6
Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
7
Department of Obstetrics and Gynecology, Copenhagen University Hospital Rigshospitalet, Copenhagen 2100, Denmark.
8
Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen 2100, Denmark.
9
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
10
Department of Obstetrics and Gynecology, Odense University Hospital, Odense 5000, Denmark.
11
Department of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Centre, New York University Langone Medical Center, New York, NY 10016, USA.
12
Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
13
Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.
14
Division of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.
15
Ludwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.
16
Howard Hughes Medical Institute, Baltimore, MD 21287, USA.
17
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.
18
Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.

Abstract

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.

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