Potter N.T.,Molecular Pathology Laboratory Network |
Hurban P.,Quintiles |
White M.N.,Molecular Pathology Laboratory Network |
Whitlock K.D.,Molecular Pathology Laboratory Network |
And 5 more authors.
Clinical Chemistry | Year: 2014
BACKGROUND: Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test. METHODS: Analytical performance at 4 testing laboratories included determination of limit of detection, precision, and reproducibility of the SEPT9 test. Clinical performance was evaluated in a prospective study by use of samples (n = 1544) from subjects enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with colonoscopy, the reference standard. RESULTS: The limit of detection for methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6-11 pg/mL) corresponding to <2 genome copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical trial, sensitivity for all stages of CRC was 68% (95% CI 53%-80%) and for stage I-III CRC, 64% (48%-77%). Adjusted specificity, on the basis of negative colonoscopy findings, was 80.0% (78%-82%). SIGNIFICANCE: The Epi proColon test is a simple, realtime PCR-based assay for the detection of methylated SEPT9 DNA in blood that may provide a noninvasive CRC screening alternative for people noncompliant with current CRC screening guidelines. © 2014 American Association for Clinical Chemistry.
Buchan B.W.,Medical College of Wisconsin |
Buchan B.W.,Dynacare Laboratories |
Peterson J.F.,Medical College of Wisconsin |
Cogbill C.H.,Medical College of Wisconsin |
And 8 more authors.
American Journal of Clinical Pathology | Year: 2011
Numerous drugs such as clopidogrel have been developed to reduce coagulation or inhibit platelet function. The hepatic cytochrome P450 (CYP) pathway is involved in the conversion of clopidogrel to its active metabolite. A recent black-box warning was included in the clopidogrel package insert indicating a significant clinical link between specific CYP2C19 genetic variants and poor metabolism of clopidogrel. Of these variants,*2 and*3 are the most common and are associated with complete loss of enzyme activity. In patients who are carriers of a CYP2C19*2 or*3 allele, the conversion of clopidogrel to its active metabolite may be reduced, which can lead to ischemic events and negative consequence for the patient. We examined the ability of the Verigene CLO assay (Nanosphere, Northbrook, IL) to identify CYP2C19*2 and*3 polymorphisms in 1,286 unique whole blood samples. The Verigene CLO assay accurately identified homozygous and heterozygous*2 and*3 phenotypes with a specificity of 100% and a final call rate of 99.7%. The assay is fully automated and can produce a result in approximately 3.5 hours. © American Society for Clinical Pathology.
Kightlinger R.S.,University of Virginia |
Irvin W.P.,Riverside Regional Medical Center |
Archer K.J.,Virginia Commonwealth University |
Huang N.W.,Thomas Jefferson University |
And 4 more authors.
American Journal of Obstetrics and Gynecology | Year: 2010
Objective: The purpose of this study was to determine the prevalence of cervical disease, human papillomavirus infection, and human papillomavirus (HPV) genotypes in indigenous villages of Guyana. Study Design: This is a retrospective analysis of a clinical cervical cancer screening and treatment program: 2250 women underwent cytologic screening; 1423 women were concomitantly screened for HPV. HPV genotyping was performed in 45 women with high-grade dysplasia and in 9 women with cervical carcinoma. Results: We found invasive cervical carcinoma in 0.80% of the women, cervical intraepithelial neoplasia II and III in 5.07% of the women, and a high-risk HPV infection rate in 19.3% of the women, all of which peaked between the ages of 20-30 years. Sixteen genotypes were detected in women with high-grade dysplasia or cancer: HPV 31, 25.0%; HPV 16, 22.7%; HPV 18, 13.6%. The rate of HPV 16 and 18 in cervical cancer was 55.50%. Conclusion: Indigenous Guyanese women have a high rate of cervical cancer and high-grade dysplasia, with an apparent predominance of HPV 16 and18 in invasive cancer and overrepresentation of HPV 31 in high-grade dysplasia. © 2010 Mosby, Inc. All rights reserved.
Quigley N.B.,Molecular Pathology Laboratory Network Inc. |
Potter N.T.,Molecular Pathology Laboratory Network |
Chivukula M.,University of Pittsburgh |
Knight M.Z.,Metropolitan Pathologists |
And 2 more authors.
Journal of Clinical Virology | Year: 2011
Background: High-risk (HR) human papillomavirus (HPV) prevalence rates, as determined by the Cervista ® HPV HR test, in women aged ≥30 years in a routine screening population have not been studied. Objectives: The primary objective of this study was to estimate HR HPV prevalence in women negative for intraepithelial lesion or malignancy (NILM) cytology using the CERVISTA HPV HR test. The study also compared HR HPV prevalence rates in women aged ≥30 years and NILM cytology using the CERVISTA HPV HR and Hybrid Capture ® 2 (hc2) tests. Study design: A multi-center study was conducted to analyze HR HPV prevalence rates using the CERVISTA HPV HR test from residual ThinPrep ® specimens. HR HPV positive rates were determined for hc2; percent agreement between the CERVISTA HPV HR and the hc2 tests were reported. Results: HR HPV prevalence rates among women with NILM cytology were not statistically different between the CERVISTA HPV HR and hc2 tests (6.92% [98/1417] versus 5.93% [84/1417], respectively; P> 0.05). The overall percent agreement between the tests was 95.3% (1351/1417; 95% confidence interval [CI]: 94.1-96.3; κ = 0.61, 95% CI: 0.53-0.70). There were no statistically significant differences between tests across age groups or investigational sites. For both tests, there was a statistically significant decrease in HR HPV positive results as age increases (CERVISTA HPV HR, P = 0.0009; hc2, P< 0.0001). Discussion: There is no statistically significant difference between HR HPV prevalence rates obtained with the CERVISTA HPV HR and hc2 tests in women aged ≥30 years with NILM cytology. © 2011 Elsevier B.V.