Epidemiology Studies Regarding HPV and Cervical Cancer
DNA Methylation as a Risk Factor for Cervical Neoplasia
Investigator: Long F. Xi
Human papillomavirus (HPV) infection plays a significant role in the development of cervical cancer. However, most infections regress spontaneously and few progress to cervical cancer. Therefore, factors other than HPV infection likely are involved in cervical carcinogenesis. Methylation of CpG islands in the promoter regions of host and viral genes can lead to loss of gene function and has been observed in a number of cancers, including cervical.
Long F. Xi has proposed to analyze whether aberrant DNA methylation of viral genes is associated with risk of cervical cancer and if detection of this marker in exfoliated cervical cell samples can identify women at high risk of developing cervical intraepithelial neoplasia grades II-III (CIN 2-3). The methylation patterns of CpG islands in a panel of genes closely related to CIN 2-3 risk will be mapped and compared between women with CIN 2-3 and women with CIN 1 or normal histology. Differential methylation pattern differences between cases and controls will be designed to detect hyper-methylated genes in cervical swab samples. The ability of this pattern to identify women with CIN 2-3 or higher grades of cervical cancer will be tested. This work will be performed using samples from the ongoing NCI-funded project, "Evaluation of Cervical Cancer Screening Methods (EVA)." This study also proposes to test whether CpG hypomethylation (implying aberrant gene activation) in the long control region of the HPV16 genome in HPV16-infected women is associated with persistence of infection, high levels of E7 mRNA, and increased risk of developing CIN 2-3.
For more information contact NCI Program Director: Mukesh Verma