title: High-risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer.
abstract: The purpose of this study was to examine the implication of high-risk human papillomavirus (HPV) load in cervical intraepithelial neoplasia (CIN) and cancer, and to detect biomarkers in cervical disease. We conducted high-risk HPV DNA load and cervical cytology tests in 343 women, cervical tissue biopsy in 143 women, and immunohistochemistry for p16(INK4A), cyclin D1, p53, cyclooxygenase-2, Ki-67, GLUT1, hPygopus2, and beta-catenin. As a result, HPV load [relative light units (RLU) value] was correlated with the histological severity of cervical disease (p < 0.05). In the 'atypical squamous cells of undetermined significance' cytology group, 2.385 of HPV load seemed to be the cut-off value at which 'benign' or CIN I can be differentiated from 'CIN II or more severe' (AUC = 0.712), but not statistically significant. The relative risk (odds ratio) of p16(INK4A) and GLUT1 overexpression increased gradually according to the histological severity of cervical disease. The p16(INK4A) showed statistically significant odds ratios in CIN II, CIN III, and cancer; GLUT1, in CIN II and CIN III; hPygopus2, in CIN III; and beta-catenin, in CIN III and cancer. Conclusively, HPV load, p16(INK4A) , and GLUT1 can be instrumental in predicting the severity of HPV-related cervical disease. The beta-catenin/hPygopus2 signaling may be involved in proceeding to CIN III.
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul; Department of Pathology, Seoul National University College of Medicine, Seoul.
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Jeon
authors.forename: Taek Sang
authors.initials: TS
authors.lastname: Lee
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Euno
authors.initials: E
authors.lastname: Choi
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Byeon
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Park
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000254:growth & development / Q000302:isolation & purification*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014626:Vaginal Smears; D019562:Viral Load; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; C495677:SLC2A1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Cervix neoplasm; GLUT1; Human papillomavirus; beta-catenin; hPygopus2; p16 INK4A