Up-regulation of Lipocalin 2 Is Associated With High-Risk Human Papillomavirus and Grade of Cervical Lesion at Baseline but Does Not Predict Outcomes of Infections or Incident Cervical Intraepithelial Neoplasia

Our objective was to assess whether neutrophil gelatinase associated lipocalin (NGAL)/lipocalin 2 (LCN2) expression in cervical human papillomavirus (HPV) lesions has implications on the outcome of HP V infections or disease progression. Cervical biopsy specimens from 225 women in the Latin American Screening study were analyzed for NG'AL/LCN2 expression using immunohistochemical analysis, to assess associations with cervical intraepithelial neoplasia (CIN) grade, high-risk HPV, and in predicting outcomes of high-risk (HR)-HP V infections. Expression of NGAL/LCN2 increased with lesion grade (odds ratio [On 3.86; 95% confidence interval [ciJ, 1.53-9.71; P =.001). Up-regulation was also related to HR-HPV detection (OR, 2.21; 95% CI, 1.15-4.24; P =.016) and showed a linear relationship to 11R-HPV load (P =.002). NGAL/LCN2 expression was of no value in predicting the outcomes of HR-HP V infections or the surrogate end points (incident CIN 1+ and GIN 2+) of progressive disease. Because the 5V40 large T antigen is a powerful up-regulator of this lipocalin, up-regulation ofNGAL/LCN2 in GIN is probably induced by HR-HP V E6 oncoprotein, most likely by eliminating its normal transcription repression exerted by wild-type p53.