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

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

doi:10.1126/scitranslmed.aap8793

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

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 AngaritaMaria 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

Institut for Klinisk Medicin

71 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	eaap8793
Tidsskrift	Science Translational Medicine
Vol/bind	10
Udgave nummer	433
Antal sider	9
ISSN	1946-6234
DOI	https://doi.org/10.1126/scitranslmed.aap8793
Status	Udgivet - 21 mar. 2018

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Wang, Y., Li, L., Douville, C., Cohen, J. D., Yen, T.-T., Kinde, I., Sundfelt, K., Kjær, S. K., Hruban, R. H., Shih, I.-M., Wang, T.-L., Kurman, R. J., Springer, S., Ptak, J., Popoli, M., Schaefer, J., Silliman, N., Dobbyn, L., Tanner, E. J., ... Papadopoulos, N. (2018). Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Science Translational Medicine, 10(433), Artikel eaap8793. https://doi.org/10.1126/scitranslmed.aap8793

Wang, Y, Li, L, Douville, C, Cohen, JD, Yen, T-T, Kinde, I, Sundfelt, K, Kjær, SK, Hruban, RH, Shih, I-M, Wang, T-L, Kurman, RJ, Springer, S, Ptak, J, Popoli, M, Schaefer, J, Silliman, N, Dobbyn, L, Tanner, EJ, Angarita, A, Lycke, M, Jochumsen, K, Afsari, B, Danilova, L, Levine, DA, Jardon, K, Zeng, X, Arseneau, J, Fu, L, Diaz, LA, Karchin, R, Tomasetti, C, Kinzler, KW, Vogelstein, B, Fader, AN, Gilbert, L & Papadopoulos, N 2018, 'Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers', Science Translational Medicine, bind 10, nr. 433, eaap8793. https://doi.org/10.1126/scitranslmed.aap8793

@article{31bdee4675d040e4853fe4b0356ef785,

title = "Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers",

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.",

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

note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2018",

month = mar,

day = "21",

doi = "10.1126/scitranslmed.aap8793",

language = "English",

volume = "10",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "american association for the advancement of science",

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T1 - Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers

AU - Wang, Yuxuan

AU - Li, Lu

AU - Douville, Christopher

AU - Cohen, Joshua D

AU - Yen, Ting-Tai

AU - Kinde, Isaac

AU - Sundfelt, Karin

AU - Kjær, Susanne K

AU - Hruban, Ralph H

AU - Shih, Ie-Ming

AU - Wang, Tian-Li

AU - Kurman, Robert J

AU - Springer, Simeon

AU - Ptak, Janine

AU - Popoli, Maria

AU - Schaefer, Joy

AU - Silliman, Natalie

AU - Dobbyn, Lisa

AU - Tanner, Edward J

AU - Angarita, Ana

AU - Lycke, Maria

AU - Jochumsen, Kirsten

AU - Afsari, Bahman

AU - Danilova, Ludmila

AU - Levine, Douglas A

AU - Jardon, Kris

AU - Zeng, Xing

AU - Arseneau, Jocelyne

AU - Fu, Lili

AU - Diaz, Luis A

AU - Karchin, Rachel

AU - Tomasetti, Cristian

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Fader, Amanda N

AU - Gilbert, Lucy

AU - Papadopoulos, Nickolas

PY - 2018/3/21

Y1 - 2018/3/21

N2 - 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.

AB - 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.

U2 - 10.1126/scitranslmed.aap8793

DO - 10.1126/scitranslmed.aap8793

M3 - Journal article

C2 - 29563323

SN - 1946-6234

VL - 10

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 433

M1 - eaap8793

ER -

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

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