The Efficacy of Genetic Biomarkers in Evaluating Precancerous Cervical Lesions

Grant Winners

Deans

Abstract

​Cervical cancer is the third most common malignancy in women worldwide, ranking 14th in the U.S. and is a leading cause of cancer-related deaths in developing countries and among those with limited access to screening in the U.S. It is estimated that approximately 12,820 new cases of invasive cervical cancer will be diagnosed in the U.S. in 2017, claiming the lives of roughly 4,210 women, despite the use of preventative screening guidelines. Currently, the standard of cervical cancer screening involves the use of papanicolaou (Pap) smear screening, along with screening for human papilloma virus ​​(HPV) infection. While this approach has improved diagnosis and reduced mortality rates tied to cervical cancer, the widespread prevalence of HPV infections has made it difficult for clinicians to determine how they should proceed with management, especially with a borderline or ambiguous Pap test result. Guidelines propose either pursuing more invasive testing or taking a watchful waiting approach, which can both be expensive, burdensome emotionally and physically to the patient and time consuming, especially since most cases do not progress to cervical dysplasia or cancer.  More recently, genetic screening of abnormalities in chromosomal DNA, as a result of HPV-associated transformations, is an emerging approach that could potentially aid clinicians in management and provide further insight in cervical pathology.  Several genetic biomarkers have been linked to the progression of transforming HPV infections to invasive cervical cancer, yet validation in clinical practice remains limited. This approach could potentially help characterize the effects of more than 14 HPV types that are considered to be cancer-causing, or high-risk, types.  Specifically, addition of chromosome 3q and 5q are the most consistently reported chromosomal abnormality in cervical cancer, suggesting that amplification in these chromosome regions could determine which HPV infections have the potential of contributing to cancer progression. In this application, we aim to determine if using genetic biomarkers found on chromosome 3q and 5p, in conjugation with standards of care, will reveal clinically relevant cervical alterations influencing clinic management and early intervention.  With these efforts, we not only hope to provide insight into cervical pathology but to aid clinicians in making more informed decisions and reduce the economic, physical and emotional burden tied to current diagnostic protocols.​