title: 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.
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.
authors.affiliation: Department of Oral Pathology, Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Stina
authors.initials: S
authors.lastname: Syrjänen
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longhato-Filho
authors.forename: Luis O
authors.initials: LO
authors.lastname: Sarian
authors.forename: Paulo
authors.initials: P
authors.lastname: Naud
authors.forename: Sophie
authors.initials: S
authors.lastname: Derchain
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rottelli-Martins
authors.forename: Silvio
authors.initials: S
authors.lastname: Tatti
authors.forename: Margherita
authors.initials: M
authors.lastname: Branca
authors.forename: Mojca
authors.initials: M
authors.lastname: Eržen
authors.forename: Luciano S
authors.initials: LS
authors.lastname: Hammes
authors.forename: Jean
authors.initials: J
authors.lastname: Matos
authors.forename: Renata
authors.initials: R
authors.lastname: Gontijo
authors.forename: Joana
authors.initials: J
authors.lastname: Bragança
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Arlindo
authors.forename: Mariana Y S
authors.initials: MY
authors.lastname: Maeda
authors.forename: Silvano
authors.initials: S
authors.lastname: Costa
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism* / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism; D008137:Longitudinal Studies; D015999:Multivariate Analysis; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015843:Serpins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000821:virology
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; D014408:Biomarkers, Tumor; D004279:DNA, Viral; D054834:Lipocalins; D015843:Serpins; C434683:serpin-2; D016753:Interleukin-10; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D005095:Exoribonucleases; C413442:SFN protein, human