Dataset Information

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6320220 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wang Yuxuan Y Li Lu L Douville Christopher C Cohen Joshua D JD Yen Ting-Tai TT Kinde Isaac I Sundfelt Karin K Kjær Susanne K SK Hruban Ralph H RH Shih Ie-Ming IM Wang Tian-Li TL Kurman Robert J RJ Springer Simeon S Ptak Janine J Popoli Maria M Schaefer Joy J Silliman Natalie N Dobbyn Lisa L Tanner Edward J EJ Angarita Ana A Lycke Maria M Jochumsen Kirsten K Afsari Bahman B Danilova Ludmila L Levine Douglas A DA Jardon Kris K Zeng Xing X Arseneau Jocelyne J Fu Lili L Diaz Luis A LA Karchin Rachel R Tomasetti Cristian C Kinzler Kenneth W KW Vogelstein Bert B Fader Amanda N AN Gilbert Lucy L Papadopoulos Nickolas N

Science translational medicine 20180301 433

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 ...[more]

PMID: 29563323

Similar Datasets

Project description:ObjectivesThe aim of this study was to identify tumor-derived DNA from Papanicolaou (Pap) smear and plasma specimens collected from patients with endometrial cancer or atypical hyperplasia (EC/AH) or epithelial ovarian cancer (OC).MethodsTumor tissues, peripheral blood, and Pap smear samples were collected from patients with EC/AH and patients with epithelial OC. Somatic mutations of tumor specimens in EC/AH and OC were examined by whole-exome sequencing using a 127-driver gene panel from The Cancer Genome Atlas (TCGA). A nine-gene EC/AH panel and an eight-gene OC panel were established based on the identified significantly mutated genes in the EC/AH and OC tumor specimens. Circulating single-molecule amplification and resequencing technology (cSMART) was applied to evaluate somatic mutations in Pap smear DNA and plasma circulating cell-free DNA (ccfDNA) using the EC/AH and OC gene panels.ResultsIn EC/AH group, there existed 22 tumors and 14 of the 22 tumors contributed hot spot mutations for the EC/AH nine-gene panel. In the Pap smear subgroup, all 21 Pap smears tested positive. Nine out of 11 (81.8%) identified the same gene mutations with their matched tumors and the remaining 10 Pap smears all tested positive. In the plasma subgroup, 10 out of 26 (38.5%) plasmas tested positive. One out of 13 (7.7%) identified the same gene mutation with its matched tumor and 5 out of the remaining 13 plasmas (38.5%) tested positive. In OC group, there existed 17 tumors and 16 of the 17 tumors contributed hot spot mutations for the OC eight-gene panel. In the Pap smear subgroup, all 11 Pap smears tested positive. Five out of 10 (50.0%) identified the same gene mutations with their matched tumors and the remaining one Pap smear also tested positive. In the plasma subgroup, all 22 plasmas tested positive. Ten out of 14 (71.4%) identified the same gene mutation with their matched tumors and the remaining 4 plasmas all tested positive.ConclusionsTumor-derived DNA can be detected in Pap smears and plasmas from patients with EC/AH or epithelial OC. Using a small gene-panel, early detection of EC/AH and OC might be promising. However, the value of plasma ccfDNA for EC/AH requires further investigation.

Project description:ImportanceThe low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease.ObjectiveTo determine whether the presence of the clonal pathogenic TP53 variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis.Design, setting, and participantsThis cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women's Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the TP53 variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019.Main outcomes and measuresThe presence of tumor pathogenic TP53 variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings.ResultsAmong 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched TP53 variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the TP53 clonal variant was detected at all time points.Conclusions and relevanceThese findings suggest that noninvasive early molecular diagnosis of HGS-EOC is potentially achievable through detection of TP53 clonal variants in the DNA purified from Papanicolaou tests performed during cervical cancer screening.

Project description:BackgroundCervical cancer remains the fourth most frequently diagnosed cancer among women, and its impact is particularly significant in women residing in less developed countries. This study aims to assess socioeconomic inequality in using Papanicolaou tests, commonly known as Pap tests, which are crucial for detecting cervical cancer. The research also seeks to decompose this inequality, identifying its contributing factors. This investigation is conducted within a sizable population-based study focused on the Kurdish population, with an additional examination of potential variations between urban and rural areas.MethodThe study utilized baseline data from the Ravansar Non-Communicable Disease Cohort Study (RaNCD), involving 3,074 ever-married women aged 35-65. Asset data was employed to determine socioeconomic status (SES), and Principal Component Analysis was applied. The uptake of Papanicolaou tests was assessed for inequality using the Concentration Index (Cn). Additionally, decomposition analysis was conducted to identify and understand the factors contributing to socioeconomic inequality.ResultsThe study found that overall, 86% of women reported having undergone cervical cancer screening at least once in their lifetime. The Concentration Index (Cn) for the total population was 0.21 (p < 0.0001), indicating a higher concentration of Papanicolaou test uptake among wealthier groups. In urban areas, the Cn was 0.34 (p < 0.0001), reflecting a significant concentration among the rich. However, in rural areas, the Cn was -0.10 (p = 0.3006), suggesting no significant socioeconomic inequality. Factors such as socioeconomic status (SES), education, and age contributed to reducing inequality, explaining 62.7%, 36.0%, and 1.7% of the observed inequality, respectively. Interestingly, place of residence had a negative influence on inequality.ConclusionThe uptake of Papanicolaou tests varies across different socioeconomic status levels, with a higher concentration among wealthier groups. The results enable health policymakers and researchers to tailor health intervention toward increasing public awareness, especially among women with lower levels of education women in economically deprived groups.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets