TY - JOUR T1 - Association of elevated E6 oncoprotein with grade of cervical neoplasia using PDZ interaction-mediated precipitation of E6. JF - J Low Genit Tract Dis Y1 - 2011 A1 - Sellors, John W A1 - Schweizer, Johannes G A1 - Lu, Peter S A1 - Liu, Bin A1 - Weigl, Bernhard H A1 - Cui, Jian Feng A1 - Peck, Roger B A1 - Lewis, Kristen A1 - Lim, Jeanette A1 - Howard, Michelle A1 - Mahoney, Charles W A1 - McAllister, Linda A1 - Berard-Bergery, Marthe A1 - Bry, Claire A1 - Labiad, Yassine A A1 - Li, Haimin A1 - Liu, Lilyn A1 - Silver, Jon A1 - Chen, Wen A1 - Qiao, You Lin KW - Adult KW - Blotting, Western KW - Cervical Intraepithelial Neoplasia KW - Cervix Uteri KW - China KW - Female KW - Human papillomavirus 16 KW - Humans KW - Immunoprecipitation KW - Middle Aged KW - Oncogene Proteins, Viral KW - Papillomavirus Infections KW - Repressor Proteins KW - Up-Regulation KW - Uterine Cervical Neoplasms AB -

OBJECTIVE: To determine the expression of human papillomavirus (HPV) type 16 E6 oncoprotein in cervical specimens of women with and without cervical intraepithelial neoplasia (CIN).

MATERIALS AND METHODS: Cervical specimens from 2,530 unscreened women aged 30 to 54 years from Shanxi, China, were obtained. All women were assessed by liquid-based cytology, high-risk HPV DNA tests, and colposcopy with directed biopsy and endocervical curettage as necessary. Women with abnormal cytologic results or positive HPV DNA results were recalled for colposcopy, 4-quadrant cervical biopsies, and endocervical curettage. Women with biopsy-proven CIN and cancer and a convenience sample of HC2-positive, disease-negative women were tested for the presence of HPV-16 infection via HPV-16 E6 DNA-specific polymerase chain reaction. A PDZ interaction-mediated E6 oncoprotein precipitation method followed by E6-specific Western blot was performed on specimens from women with HPV-16 infections. Associations between elevated expression of E6 oncoprotein and CIN 2 and 3 were determined using logistic regression and a reference category of CIN 1 and disease-negative.

RESULTS: A significant trend for the detection of HPV-16 E6 oncoprotein in specimen of women with proven HPV-16 infection was determined: 0% (0/12), 12.5% (1/8), 36.4% (4/11), and 42.9% (3/7) of those with negative findings, CIN 1, 2, and 3, respectively (p = .01). Compared with the category combining negative findings and CIN 1, detection of E6 oncoprotein was associated with CIN 2 (odds ratio = 10.9, p = .05) and CIN 3 (odds ratio = 14.3, p = .04).

CONCLUSIONS: There is a significant association between elevated expression of E6 oncoprotein and grade of CIN. This finding seems consistent with the role played by E6 oncoprotein in carcinogenesis.

VL - 15 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21478701?dopt=Abstract ER - TY - JOUR T1 - A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China. JF - Lancet Oncol Y1 - 2008 A1 - Qiao, You-Lin A1 - Sellors, John W A1 - Eder, Paul S A1 - Bao, Yan-Ping A1 - Lim, Jeanette M A1 - Zhao, Fang-Hui A1 - Weigl, Bernhard A1 - Zhang, Wen-Hua A1 - Peck, Roger B A1 - Li, Ling A1 - Chen, Feng A1 - Pan, Qing-Jing A1 - Lorincz, Attila T KW - Adult KW - Alphapapillomavirus KW - Cervical Intraepithelial Neoplasia KW - China KW - Cross-Sectional Studies KW - DNA, Viral KW - Female KW - Humans KW - Mass Screening KW - Middle Aged KW - Papillomavirus Infections KW - Predictive Value of Tests KW - ROC Curve KW - Rural Health Services KW - Sensitivity and Specificity KW - Tumor Markers, Biological KW - Uterine Cervical Neoplasms AB -

BACKGROUND: A new test (careHPV; QIAGEN, Gaithersburg, MD, USA) has been developed to detect 14 high-risk types of carcinogenic human papillomavirus (HPV) in about 2.5 h, to screen women in developing regions for cervical intraepithelial neoplasia (CIN). We did a cross-sectional study to assess the clinical accuracy of careHPV as a rapid screening test in two county hospitals in rural China.

METHODS: From May 10 to June 15, 2007, the careHPV test was done locally by use of self-obtained vaginal and provider-obtained cervical specimens from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi province, China. All women were assessed by visual inspection with acetic acid (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and colposcopy with directed biopsy and endocervical curettage as necessary. In 2388 women with complete data, 441 women with negative colposcopy, but unsatisfactory or abnormal cytology or who were positive on HC2 or the new careHPV test, were recalled for a second colposcopy, four-quadrant cervical biopsies, and endocervical curettage. An absence of independence between the tests was not adjusted for and the Bonferroni correction was used for multiple comparisons.

FINDINGS: Complete data were available for 2388 (94.4%) women. 70 women had CIN2+ (moderate or severe CIN or cancer), of whom 23 had CIN3+. By use of CIN2+ as the reference standard and area-under-the-curve analysis with a two-sided alpha error level of 0.0083, the sensitivities and specificities of the careHPV test for a cut-off ratio cut-point of 0.5 relative light units, were 90.0% (95% CI 83.0-97.0) and 84.2% (82.7-85.7), respectively, on cervical specimens, and 81.4% (72.3-90.5) and 82.4% (80.8-83.9), respectively, on vaginal specimens (areas under the curve not significantly different, p=0.0596), compared with 41.4% (29.9-53.0) and 94.5% (93.6-95.4) for VIA (areas under the curve significantly different, p=0.0001 and p=0.0031, for cervical and vaginal-specimen comparisons for the careHPV test, respectively). The sensitivity and specificity of HC2 for cervical specimens were 97.1% (93.2-100) and 85.6% (84.2-87.1), respectively (areas under the curve not significantly different from the careHPV test on cervical specimens, p=0.0163).

INTERPRETATION: The careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions.

VL - 9 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/18805733?dopt=Abstract ER - TY - JOUR T1 - A magnetic immunochromatographic strip test for detection of human papillomavirus 16 E6. JF - Clin Chem Y1 - 2006 A1 - Peck, Roger B A1 - Schweizer, Johannes A1 - Weigl, Bernhard H A1 - Somoza, Chamorro A1 - Silver, John A1 - Sellors, John W A1 - Lu, Peter S KW - Antibodies, Monoclonal KW - Chromatography KW - Enzyme-Linked Immunosorbent Assay KW - Female KW - Human papillomavirus 16 KW - Humans KW - Magnetics KW - Oncogene Proteins, Viral KW - PDZ Domains KW - Protein Binding KW - Protein Interaction Mapping KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Sensitivity and Specificity VL - 52 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/18084827?dopt=Abstract ER -