Abstract 3478: Gene expression profiles from exfoliated cervical cells identify potential biomarkers predictive of HPV16 clearance or persistence.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Cervical cancer is the second most common cancer in women worldwide with about 500,000 new cases and 250,000 deaths annually. The incidence of cervical cancer has dramatically decreased in developed countries over the past fifty years, mainly due to effective Pap test screening and follow-up programs that allow for early detection and treatment. However, many abnormal cervical lesions detected by the Pap test would spontaneously regress if not treated; therefore current screening and follow-up protocols result in expensive and painful interventions that also may compromise future pregnancies. The etiologic agent of cervical cancer is sexually-transmitted, high-risk human papillomavirus (HR-HPV), with HPV16 being responsible for 50% of all cervical cancer. Most women will acquire HR-HPV at some point during their lifetime; however most of these infections clear within 9-18 months. Only women with persistent HR-HPV infection are truly at risk of developing cervical cancer. Biomarkers that would identify women at risk for persistent HR-HPV infection would allow physicians to follow these patients, sparing others unnecessary and costly follow-up. We have performed microarray gene expression profiling, using Agilent 4x44K human microarrays, on five HPV16 positive exfoliated cervical cell samples collected in RNAlater (Ambion) from women who cleared an HPV16 infection, and eight HPV16 positive cervical cell samples from women with persistent HPV16 infection, defined as being positive for HPV16 for at least one year. Data analysis was performed using limma/limmaGUI (Bioconductor), GeneSifter (Geospiza), and Cluster/Treeview (Eisen Lab) software. Using the nonparametric Wilcoxon rank-sum test and 0.01 and 2 as p-value and fold change cutoffs, respectively, we identified 391 differentially expressed genes in HPV16 persisters as compared to HPV16 clearers. In addition, we identified a molecular signature composed of 14 genes that separates the samples into their corresponding groups (persisters and clearers) when studied by both cluster analysis and correlation analysis. Expression of 4 immune-related genes (IL6, IL1A, IL1B and TNF-alpha) was also determined by quantitative real time PCR. Expression of all four genes was confirmed to be downregulated in HPV16 persisters as compared to HPV16 clearers. These 4 potential biomarker genes, and others to be validated, have potential clinical importance, since they can predict if HPV16 infections will be persistent or will be cleared. We are currently validating these initial results with a second, much larger validation set of exfoliated cervical cells collected from women that had persistent HPV16 infections or were able to clear the HPV16 infection. Supported by grant P20MD001770 from the NIH/NIMHD Citation Format: Diego Altomare, Susannah Kassler, Carolyn Banister, Amy Messersmith, Saundra Glover, Lucia Pirisi-Creek, Kim E. Creek. Gene expression profiles from exfoliated cervical cells identify potential biomarkers predictive of HPV16 clearance or persistence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2013-3478