Abstract 1745: Comorbidity factors associated with human papillomavirus infectivity: Implications in cervical cancer health disparity

Objective: High-risk strains of human papillomavirus (HPV), HPV E6/E7 cause cervical cancer (CxCa). Certain underserved populations in the United States, such as American Indian and African American women disproportionately suffer from CxCa compared to their Caucasian counter parts. However, precise etiology and comorbidity factors associated with CxCa health disparity are not fully uncovered. Understanding of these factors at molecular level will entail developing novel strategies to reduce this health disparity. In this study, we have investigated the molecular interplay existing between various comorbidity factors, namely, smoking, alcohol and HIV co-infection on the HPV infectivity which are primarily known for the progression of CxCa. Method: In order to define a molecular association of smoking, alcohol and HIV co-infection with CxCa, Caski and SiHa (HPV infected cervical cancer cells) cells were treated with a smoking carcinogens Benzo[a]Pyrene (BaP) or alcohol (EthOH) or both for different time periods. Effects of these treatment was analyzed on cell proliferation, clonogenicity, cell migration, cell cycle and the expression of HPV E6/E7 was determined by qRT-PCR, immunoblotting and confocal microscopy. The effect of HIV co-infection on the expression of HPV E6/E7 was also investigated by incubating CxCa cells with conditioned medium derived from HIV infected U937 monocytic cells (U1). Additionally, we examined effect of these cofactors on the expression enzymes associated with cellular oxidative stress using immunoblotting and confocal microscopy analyses. Result: Our results show that the exposure of BaP or EthOH or their combination enhances the expression of HPV E6/E7 oncogenes. Additionally, cells treated with BaP and EthOH alone or in combination show higher oncogenic phenotypes as evident by increased cell proliferation, clonogenicity and cell migration andinvasion. These cofactors in presence of HIV co-infection also augment the expression of HPVE6/E7 oncogenes. Exposure of these cofactors alter cellular oxidative stress via modulation of the expression of PRDX6 enzyme. Interestingly, curcumin and its nanoparticle formulation (Nano-Cur) effectively inhibits BaP/EthOH induced expression of E6/E7 oncogenes, growth, migration of CxCa cells and induces apoptosis. Conclusions: The study suggests a molecular link between smoking, alcohol and HIV infection with HPV infectivity and their potential association with CxCa health disparity. These event