"Molecular Pap Biomarkers for Cervical Cancer Risk Assessment in ThinPr" by Jennifer Taylor

Author(s)

Jennifer Taylor

Date Approved

3-2014

Document Type

Thesis

Degree Name

Master of Science in Molecular Pathology and Immunology

Department

Molecular Biology

College

Graduate School of Biomedical Sciences

First Advisor

Salvatore Caradonna, PhD

Committee Member 1

Lisa Huang, PhD

Committee Member 2

Jason Trama, PhD

Committee Member 3

Lyndi Rice, PhD

Subject(s)

Neoplasms; Uterine Cervical Neoplasms; Human Papillomavirus; Diagnostic Tests; In Situ Hybridization

Disciplines

Cancer Biology | Cell Biology | Diagnosis | Immunology and Infectious Disease | Medical Molecular Biology | Medicine and Health Sciences | Molecular Biology | Neoplasms | Virus Diseases

Abstract

Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of true dysplastic or neoplastic cells in cervical tests would therefore avoid emotional distress for many patients and eliminate unnecessary pathology and follow-up care costs. This present study demonstrated that in situ hybridization (ISH) is a qualitative molecular diagnostic test for the detection of HPV E6/E7 DEK, CIP2A, Birc5, and PME-1 mRNA. This method distinguished each candidate biomarker in Hela and SiHa cell lines and detected down to 1 % of Hela cells in a heterogeneous population. The method was compared to polymerase chain reaction (PCR), and after assessing the results, the comparison showed an exceptional agreement. Further optimization of the ISH method is needed if it is to be able to detect biomarker mRNA expression in clinical ThinPrep samples. Such a clinical assay would allow for earlier detection of precancerous lesions in patient populations and the prevention of cancer progression.

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