Competing-risks regression models in analysis of biomarkers as predictors of high-risk human papillomavirus (HPV) infection outcomes and incident CIN in the LAMS cohort

Int J Gynecol Pathol. 2013 Jul;32(4):406-15. doi: 10.1097/PGP.0b013e31826739b1.

Abstract

To assess the prediction potential of a 5-biomarker panel for detecting high-risk human papillomavirus (HR-HPV) infections and/or cervical intraepithelial neoplasia (CIN) progression. Five biomarkers, lipocalin, plasminogen activator inhibitor-2, p300, interleukin-10, and stratifin, were assessed in cervical biopsies from 225 women of the Latin American Screening Study. Competing-risks regression models were constructed to assess their predictive power for (i) HR-HPV outcomes (negative, transient, or persistent infection) and (ii) CIN outcomes (no progression, incident CIN1, CIN2, or CIN3). p300, LCN2, stratifin were significantly associated with prevalent HR-HPV but lost their significance in multivariate analysis. In the multivariate model, only p300 was an independent predictor of CIN3 (odds ratio=2.63; 95% confidence interval, 1.05-6.61; P=0.039). In univariate competing-risks regression, lipocalin predicted permanent HR-HPV-negative status, but in the multivariate model, IL-10 emerged as a independent predictor of HPV-negative status (subhazard ratio=4.04; 95% confidence interval, 1.81-9.01; P=0.001). The clinical value of the panel in predicting longitudinal outcomes of HR-HPV infection and/or incident CIN is limited.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Biomarkers / metabolism
  • Biomarkers, Tumor / metabolism
  • Cervix Uteri / metabolism*
  • Cervix Uteri / virology
  • Cohort Studies
  • DNA, Viral / genetics
  • Disease Progression
  • E1A-Associated p300 Protein / metabolism
  • Exoribonucleases / metabolism
  • Female
  • Humans
  • Interleukin-10 / metabolism
  • Lipocalins / metabolism
  • Longitudinal Studies
  • Multivariate Analysis
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / virology
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Serpins / metabolism
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / virology

Substances

  • 14-3-3 Proteins
  • Biomarkers
  • Biomarkers, Tumor
  • DNA, Viral
  • Lipocalins
  • Serpins
  • serpin-2
  • Interleukin-10
  • E1A-Associated p300 Protein
  • EP300 protein, human
  • Exoribonucleases
  • SFN protein, human