The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E 2 levels

Daniel W. Fitzgerald, Karl Bezak, Oksana Ocheretina, Cynthia Riviere, Thomas C. Wright, Ginger L. Milne, Xi Kathy Zhou, Baoheng Du, Kotha Subbaramaiah, Erin Byrt, Matthew L. Goodwin, Arash Rafii, Andrew J. Dannenberg

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28 Scopus citations

Abstract

Human immunodeficiency virus (HIV-1) infection causes chronic inflammation. COX-2-derived prostaglandin E 2 (PGE 2) has been linked to both inflammation and carcinogenesis. We hypothesized that HIV-1 could induce COX-2 in cervical tissue and increase systemic PGE 2 levels and that these alterations could play a role in AIDS-related cervical cancer. Levels of cervical COX-2 mRNA and urinary PGE-M, a biomarker of systemic PGE 2 levels, were determined in 17 HIV-negative women with a negative cervical human papilloma virus (HPV) test, 18 HIV-infected women with a negative HPV test, and 13 HIV-infected women with cervical HPV and high-grade squamous intraepithelial lesions on cytology. Cervical COX-2 levels were significantly associated with HIV and HPV status (P = 0.006 and 0.002, respectively). Median levels of urinary PGE-M were increased in HIV-infected compared with uninfected women (11.2 vs. 6.8 ng/mg creatinine, P = 0.02). Among HIV-infected women, urinary PGE-M levels were positively correlated with plasma HIV-1 RNA levels (P = 0.003). Finally, levels of cervical COX-2 correlated with urinary PGE-M levels (P = 0.005). This study shows that HIV-1 infection is associated with increased cervical COX-2 and elevated systemic PGE 2 levels. Drugs that inhibit the synthesis of PGE 2 may prove useful in reducing the risk of cervical cancer or systemic inflammation in HIV-infected women.

Original languageEnglish
Pages (from-to)34-40
Number of pages7
JournalCancer Prevention Research
Volume5
Issue number1
DOIs
StatePublished - Jan 2012

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    Fitzgerald, D. W., Bezak, K., Ocheretina, O., Riviere, C., Wright, T. C., Milne, G. L., Zhou, X. K., Du, B., Subbaramaiah, K., Byrt, E., Goodwin, M. L., Rafii, A., & Dannenberg, A. J. (2012). The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E 2 levels. Cancer Prevention Research, 5(1), 34-40. https://doi.org/10.1158/1940-6207.CAPR-11-0496