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 (IL1ß), 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. IL1ß 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 (IL1ß), 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.

HPV high risk and protective behaviors: the effects of religious affiliation.

The majority of Americans identify themselves as belonging to some religious group. There is a mixed body of literature on whether or not religious affiliation has an influence on engaging in risky behaviors among young adults attending college. This study examined associations between religious affiliation, risky sexual practices, substance use, and family structure among a sample of predominantly white college females attending a southeastern university. Given the high risk of acquiring genital human papillomavirus infection as a result of high risk sexual practices, gaining a better understanding of how religious affiliation can be used to promote healthy sexual behaviors is warranted.

Role of micro-RNAs in regulation of lentiviral latency and persistence.

Small interfering RNAs have been demonstrated to serve as a molecular defence against numerous retroviruses in plants and insects and, more recently, in primates. With the recent findings of micro-RNAs (miRNAs) that seem to play a pivotal role in the survival of the host, we have explored the role of miRNAs in lentiviral (LV) replication. We have previously hypothesized that, at least in the case of lentivirus infection, small interfering RNAs are involved in the inhibition of these types of viruses by the formation of intramolecular triplex formation (triplexes) between the polypurine tracks sequences of LV provirus and miRNAs and blocking the viral replication at the preintegration complex levels, placing these viruses into a suspended latency. Using several latently and chronically infected LV cell lines and human PBMCs from HIV-1-infected individuals, we show that perinuclear triplexes are formed in LV-infected cells. The number of triplexes decreased in cells with productive replication of LVs. Therefore, the degree of replication of HIV-1 and other LVs, both in the HIV-1 or other LV-infected cell lines and the HIV-1 infected PBMCs, inversely correlate with the number of cytoplasmic triplexes present in a particular cell. This correlation was further confirmed by the stimulation of PBMCs and LV-infected cell lines with appropriate mitogens. Treatment with Tagetin, a RNA polymerase III inhibitor, resulted in a significant decrease in triplexes and a dramatic increase in the LV replication. Our data suggest that triplex formation may be an important mechanism of LV latency mediated by endogenous miRNAs.

Cervical cancer disparities in South Carolina: an update of early detection, special programs, descriptive epidemiology, and emerging directions.

Through careful examination of cervical cancer incidence and mortality rates and current resources available in South Carolina, we have identified research and intervention priorities related to cervical cancer that would best serve the women of this state. Mortality rates due to cervical cancer are largely explained by the lack of early detection among women rarely and never screened and non-adherence to recommended follow-up care of cervical dysplasia; however, other factors less well explained are determinants of observed disparities between AA and EA women. Efforts are underway to implement strategies recommended by the NCI to eliminate cervical cancer disparities through improved efforts to reach out to rarely and never-screened women and prepare health care providers for implementation of HPV vaccines.