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- Title
Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.
- Authors
Wang, Yuxuan; Li, Lu; Douville, Christopher; Cohen, Joshua D.; Yen, Ting-Tai; Kinde, Isaac; Sundfelt, Karin; Kjær, Susanne K.; Hruban, Ralph H.; Shih, Ie-Ming; Wang, Tian-Li; Kurman, Robert J.; Springer, Simeon; Ptak, Janine; Popoli, Maria; Schaefer, Joy; Silliman, Natalie; Dobbyn, Lisa; Tanner, Edward J.; Angarita, Ana
- Abstract
Endometrial and ovarian cancers can be detected through the analysis of DNA from Pap test fluids, intrauterine samples, and plasma. Brushing up on early cancer detection: Despite the many recent advances in cancer diagnosis and treatment, ovarian cancer remains one of the most lethal malignancies, in part because there are no accurate screening methods for this disease and it is often diagnosed at a late stage. To develop a screening tool for ovarian and endometrial cancers, Wang et al. combined genetic analysis of fluids obtained through routine Papanicolau testing, normally done for cervical cancer, with analysis of tumor DNA circulating in the blood. The authors also used intrauterine sampling with Tao brushes to further increase the sensitivity of detection for the less accessible tumors. 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.
- Subjects
OVARIAN cancer; ENDOMETRIAL cancer; PAP test; POLYMERASE chain reaction; SOMATIC mutation
- Publication
Science Translational Medicine, 2018, Vol 10, Issue 433, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.aap8793