Human papillomavirus (HPV) infection is the most common viral sexually transmitted infection (STI), and infection with high-risk types of HPV has been implicated in the majority of anogenital malignancies. Worldwide, HPV-related cervical cancer is the second most common cause of malignancy in women. Over the past 40 years in the United States, cervical cancer incidence rates have been dramatically reduced, which is believed to be the result of Pap smear screening. Incidence rates are distinctly increased in minority, underserved populations. In the United States, African American women have 30% higher incidence of cervical cancer and a 2-fold increased risk of mortality as compared to Caucasian women. These findings are more striking in Louisiana, where African American women have almost a 50% increase in incidence and a 3-fold increase in mortality over their Caucasian counterparts. Even in the African-American population, where HPV infection rates are high, relatively few women progress to cervical abnormalities. This fact indicates that HPV infection is necessary but not sufficient for the development of cervical cancer. Thus, other cofactors must augment the oncogenic potential of HPV. The known oncogenic virus, Epstein-Barr virus (EBV), is shed from the cervix, making this a prime co-factor candidate for HPV-related cervical dysplasia. Preliminary data strongly suggest that EBV may be a co-factor to HPV in the pathogenesis of cervical dysplasia, irrespective of HIV status. It is hypothesized that HIV-negative women who shed both EBV and high-risk HPV from their cervix are at greater risk for cervical dysplasia than women who shed only high-risk HPV. From this hypothesis, it is predicted that (1) the rate of cervical dysplasia will be increased in those women co-shedding both EBV and HPV;(2) EBV and HPV cervical shedding will be detected prior to the development of cervical dysplasia;(3) EBV and HPV will be located in the same cervical epithelial cells or in close proximity;(4) analysis of co-infected cervical tissue will demonstrate loss of cell cycle control pathways and inhibition of apoptosis pathways;and (5) prophylactic HPV vaccination will prevent these events.

Public Health Relevance

HPV causes cervical cancer, which is disproportionately seen in minority populations. This study will further explore an interaction between HPV and EPV in the genesis of cervical cancer in a predominately African-American, underserved population. An improved understanding of this interaction could lead to improved diagnostics and therapeutic approaches to this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD004817-04
Application #
8434770
Study Section
Special Emphasis Panel (ZMD1-PA)
Project Start
2013-03-05
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$121,916
Indirect Cost
$17,424
Name
Dillard University
Department
Type
DUNS #
062665468
City
New Orleans
State
LA
Country
United States
Zip Code
70122
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