Posters
Presenting Author Academic/Professional Position
Faculty
Academic Level (Author 1)
Faculty
Discipline/Specialty (Author 1)
Immunology and Microbiology
Academic Level (Author 4)
Faculty
Discipline/Specialty (Author 4)
Immunology and Microbiology
Presentation Type
Poster
Discipline Track
Community/Public Health
Abstract Type
Research/Clinical
Abstract
Clinical studies 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 suggest that several genes are involved in different molecular pathways, which can influence the vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical studies 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 are 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 the 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, and 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, PTGS2, and EMT markers in CaSki cells 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 exacerbates HIV-1 replication in differentiated U1 cell lines via transferring CYPs and HPV oncoproteins through extracellular vehicles. Taken together, our results demonstrate that a molecular link between smoking and HIV infections in HPV cooperativity in cervical carcinogenesis might also be responsible for cervical cancer disparity among underserved populations.
Recommended Citation
Kashyap, Vivek Kumar; Sinha, Namita; Zafar, Nadeem; Yallapu, Murali M.; Kumar, Santosh; Cobos, Everardo; and Chauhan, Subhash C., "Confounding Factors of Cervical Carcinogenesis and Cervical Cancer Health Disparity" (2025). Research Symposium. 184.
https://scholarworks.utrgv.edu/somrs/2025/posters/184
Included in
Immunology of Infectious Disease Commons, Medicine and Health Sciences Commons, Microbiology Commons
Confounding Factors of Cervical Carcinogenesis and Cervical Cancer Health Disparity
Clinical studies 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 suggest that several genes are involved in different molecular pathways, which can influence the vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical studies 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 are 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 the 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, and 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, PTGS2, and EMT markers in CaSki cells 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 exacerbates HIV-1 replication in differentiated U1 cell lines via transferring CYPs and HPV oncoproteins through extracellular vehicles. Taken together, our results demonstrate that a molecular link between smoking and HIV infections in HPV cooperativity in cervical carcinogenesis might also be responsible for cervical cancer disparity among underserved populations.
