DOI

https://doi.org/10.25772/87H0-QZ92

Defense Date

2023

Document Type

Thesis

Degree Name

Master of Science

Department

Microbiology & Immunology

First Advisor

Molly Bristol

Abstract

High-risk human papillomaviruses (HPV), like HPV16 and HPV18, are associated with malignant cancer growth within the oropharynx and cervix. Globally, HPV-induced cancers, including oropharyngeal and cervical cancers, contribute 5% to the overwhelming burden of all cancers. HPV is highly transmissible by sexual contact via micro abrasions to the mucosa. Once exposure occurs, the virus begins replication and creates an intimate relationship with the host’s cellular proteins. While most HPV is cleared quickly by our immune system, persistent infections, or infections in immune compromised individuals, are susceptible to transformation and tumor progression. Early detection measures like PAP smears and preventable measures like vaccines have reduced the overall incidence of HPV. However, there are no early detections for HPV-induced oropharyngeal cancers leading to a late diagnosis after tumor establishment. While HPV-positive cancers respond better to therapeutic treatment than HPV-negative cancers, they still receive the same treatment approaches. Moreover, the morbidity associated with these treatments leads to significant loss of quality of life. For this reason, it is important to develop HPV specific treatments to target these cancers.

The Bristol laboratory is interested in evaluating therapeutic options to target the virus and specifically treat HPV-positive tumors. Estrogen receptor alpha (ERα) is a common therapeutic target in various cancers and is associated with HPV-induced cancers. When expanding our estrogen treatment to in vivo models, we no longer observed estrogenic sensitization. Although in vitro cell culture models allow us to study the virus efficiently, we must acknowledge that tumors exist within a multi-complex environment in animals; that complexity can alter responses to therapeutics. Therefore, in order to create a model for therapeutic options for HPV-positive individuals, we must understand the relationship between the tumor microenvironment (TME) and HPV. The results generated in this study show that the addition of fibroblast support cells in vitro may better predict translational medicine.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-11-2023

Included in

Dentistry Commons

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