Abstract 4965: Cooperativity of HIV and HPV co-infection contributes to cervical carcinogenesis and cervical cancer health disparity

Clinical study show that cervical cancer is the most frequently detected cancer in women living with human immunodeficiency virus (HIV) which has been defined as an acquired immunodeficiency syndrome (AIDS). Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervical cancer cases are attributable to HIV. Studies suggests that several genes are involved in different molecular pathways which can influence vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical study have also shown levels of cervical COX-2 are increased in HIV-infected and HIV/HPV-coinfected women. However, the precise molecular level interactions between HPV and HIV co-infection is not well defined. Further, smoking is well documented among HIV-positive women, but very little is known about the smoking induced molecular mechanism of HPV-HIV co infections. In this study, we investigated the interplay between smoking and HIV/HPV co-infection infectivity and their cooperativity. To check the influence of HIV-HPV co-infection at molecular level, cervical cancer cells, CaSki, were treated with U1(HIV-1-infected U937 cells) cell culture supernatant (UCS) and U937 (HIV-1 noninfected cells) culture supernatant (U9CS) every day for 4 days. To differentiate the U1 cells into macrophages, U1 cells were treated with 100 nM phorbol 12-myristate 13-acetate (PMA) for 3 days. For the treatment of smoking components, both U937 and U1 cells were treated with benzo[a]pyrene (B[a]P) at 100 nM every 24 hours for 4 days. Similarly, we treated HIV infected (U1) and noninfected (U937) cells were treated with HPV infected (CaSki) cells supernatant to determine if HPV infection can influence HIV replication related molecular pathways. Our study demonstrated that HIV-HPV-co-infection and/or B[a]P enhanced cell proliferation, colony formation, migration, and invasion as demonstrated by MTS, wound healing, boyden chamber assay respectively in CaSki cells. HIV-HPV-co-infection and/or B[a]P enhanced also induced the expression of HPV16 E6/E7, HIF-1α, COX-2 and EMT markers in CaSki cell as determined by qRT-PCR and immunoblotting. Furthermore, our qRT-PCR results demonstrated that cytokine IL-6, IL-8, IP-10, MCP-1, IL-1α, IL-10, MIP-1β TNF-α, IFN-γ and G-CSF were significantly increased in CaSki cell treated with UCS and B[a]P. We have also demonstrated that the supernatant of cervical cancer cells exacerbate HIV-1 replication in differentiated U1 cell line via transferring CYPs and HPV oncoproteins through extracellular vesicles. Taken together, our results demonstrate that a molecular link between smoking, HIV infections in HPV cooperativity in cervical carcinogenesis that might also be responsible for cervical cancer disparity among underserved populations. Citation Format: Vivek Kumar Kashyap, Namita Sinha, Nadeem Zafar, Santosh Kumar, Murali M. Yallapu, Everardo Cobos, Subhash C. Chauhan. Cooperativity of HIV and HPV co-infection contributes to cervical carcinogenesis and cervical cancer health disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4965.