title: The expression of epidermal growth factor receptor, vascular endothelial growth factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human papilloma viral load and persistence of human papillomavirus after conization with negative margins.
abstract: The aim of this study was to investigate the correlations between human papillomavirus (HPV) load and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk HPV clearance or persistence after conization with negative margins. The following samples were analyzed: 77 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II testing was used to detect HPV DNA. VEGF expression was significantly associated with HPV load (rho = 0.27186, P = 0.0191), while COX-2 expression was significantly and inversely associated with HPV load (rho = -0.34309, P = 0.0028). In univariate analysis, HPV load (P = 0.0112) and VEGF expression (P = 0.0274) were significantly associated with high-risk HPV clearance or persistence after conization with negative margins. In multiple regression analysis, high viral load (relative light unit/positive control > 500) and positive VEGF expression were significantly associated with high-risk HPV persistence after conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891-51.994; OR: 6.661, CI: 1.208-36.722, respectively). In conclusion, VEGF expression is related to HPV load, while COX-2 expression is inversely related to HPV load, and immunohistochemical analysis of VEGF expression and HPV viral load are a significant and an independent prognostic indicator of high-risk HPV persistence after conization with negative margins.
authors.affiliation: Department of Obstetrics, School of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Song
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Hur
authors.forename: I
authors.initials: I
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Saw
authors.forename: Y K
authors.initials: YK
authors.lastname: Park
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000302:isolation & purification / Q000502:physiology*; D015415:Biomarkers; D019092:Conization; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000821:virology*; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D019562:Viral Load
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2