Clinical Utility of Molecular Biomarkers in Cervical Squamous Intraepithelial Lesions in a Young Adult Population.

Objective: Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop SIL/CIN and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college-aged women.

Materials And Methods: Freshman female students were recruited into the Carolina Women's Care Study, which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of Frizzled (FZD), growth differentiating factor 15, interleukin 1 beta (IL1β), and N-cadherin was assessed through real-time polymerase chain reaction. Statistical analysis was performed with a Student t test; all results were standardized with glyceraldehyde 3-phosphate dehydrogenase.

Results: Fifty samples were selected that reflected the demographics of the Carolina Women's Care Study participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p = .0018); low-grade squamous intraepithelial lesion had 12.7-fold higher expression than negatives (p = .0011). The FZD mRNA expression was 5.7-fold higher in CIN 2 as compared with CIN 1 (p = .0041) and 8.5-fold higher compared with cytology/pathology negative (p = .0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition.

Conclusions: It seems that several biomarkers involved in the cytokine/inflammatory pathway (IL1β), cell adhesion pathway (N-cadherin), growth factor (growth differentiating factor 15), and Wingless (WNT) signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN 3 and cervical cancer.