High-risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer

APMIS. 2014 May;122(5):427-36. doi: 10.1111/apm.12163. Epub 2013 Sep 11.

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.

Keywords: Cervix neoplasm; GLUT1; Human papillomavirus; beta-catenin; hPygopus2; p16 INK4A.

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor / metabolism*
  • Cervix Uteri / cytology
  • Cervix Uteri / pathology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • DNA, Viral / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Papillomaviridae / growth & development
  • Papillomaviridae / isolation & purification*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Vaginal Smears
  • Viral Load*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • CTNNB1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Glucose Transporter Type 1
  • Ki-67 Antigen
  • SLC2A1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Cyclin D1
  • Cyclooxygenase 2
  • PTGS2 protein, human