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.
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.
|Sanabria-Salas, María Carolina; Hernández-Suárez, Gustavo; Umaña-Pérez, Adriana et al. (2017) IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry. Sci Rep 7:41920|
|Loupe, Jacob M; Miller, Patrick J; Crabtree, Judy S et al. (2017) Acquisition of an oncogenic fusion protein is sufficient to globally alter the landscape of miRNA expression to inhibit myogenic differentiation. Oncotarget 8:87054-87072|
|Rawlik, Konrad; Rowlatt, Amy; Sanabria-Salas, María Carolina et al. (2017) Evidence of epigenetic admixture in the Colombian population. Hum Mol Genet 26:501-508|
|Garay, Jone; Piazuelo, M Blanca; Lopez-Carrillo, Lizbeth et al. (2017) Increased expression of deleted in malignant brain tumors (DMBT1) gene in precancerous gastric lesions: Findings from human and animal studies. Oncotarget 8:47076-47089|
|Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo et al. (2016) High prevalence of luminal B breast cancer intrinsic subtype in Colombian women. Carcinogenesis 37:669-676|
|Joseph, Ann Mary; Srivastava, Ratika; Zabaleta, Jovanny et al. (2016) Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects. Cancer Immunol Res 4:708-16|
|Dai, Lu; Bai, Lihua; Lin, Zhen et al. (2016) Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget 7:47052-47060|
|Maxi, John K; Dean, Matt; Zabaleta, Jovanny et al. (2016) Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques. Biomolecules 6:|
|Loupe, J M; Miller, P J; Bonner, B P et al. (2016) Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion. Oncogenesis 5:e246|
|Loupe, Jacob M; Miller, Patrick J; Bonner, Benjamin P et al. (2016) Acquisition of an oncogenic fusion protein serves as an initial driving mutation by inducing aneuploidy and overriding proliferative defects. Oncotarget 7:62814-62835|
Showing the most recent 10 out of 23 publications