Date of Award

2010

Document Type

Campus Access Dissertation

Department

Biomedical Science

First Advisor

Kim E. Creek

Abstract

Human papillomavirus (HPV) is the causative agent in almost all cervical cancers. Most HPV infections are resolved by the cell-mediated immune response of the host. However, in a small subset of individuals exposed to genital HPV, infection persists and can progress to cervical carcinoma. The inability to maintain the appropriate cytokine milieu in the cervical mucosa has been implicated in HPV persistence. The switch from a predominantly Type 1 cytokine response to a predominantly Type 2 cytokine response is well-documented in advanced cervical lesions and cervical cancer samples. The cause of the cytokine imbalance in some individuals in response to HPV infection has yet to be identified. The Carolina Women's Care Study (CWCS) was established to elucidate the possible causes of the cytokine imbalance in response to HPV infection and to identify biomarkers that could augment current clinical screening protocols. Cytokine levels in cervical mucus and single nucleotide polymorphisms (SNPs) in cytokine genes were examined to detect any associations with HPV persistence. Several significant differences in cervical cytokine levels were identified between individuals who clear HPV infection and those who do not clear HPV infection within 18 months. The cytokines in which significant differences were most frequently identified were proinflammatory cytokines. The significant differences detected in proinflammatory cytokines supports the belief that inflammation is a cofactor for HPV in cervical carcinogenesis. Although additional observation would be necessary to detect biomarkers that could have clinical applications, the association of high levels of proinflammatory cytokine activation early in HPV infection represents a novel explanation for cytokine dysregulation associated with HPV carcinogenesis.

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