The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E2 levels.

Fitzgerald DW, Bezak K, Ocheretina O, Riviere C, Wright TC, Milne GL, Zhou XK, Du B, Subbaramaiah K, Byrt E, Goodwin ML, Rafii A, Dannenberg AJ
Cancer Prev Res (Phila). 2012 5 (1): 34-40

PMID: 22135046 · PMCID: PMC3252428 · DOI:10.1158/1940-6207.CAPR-11-0496

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.

©2011 AACR.

MeSH Terms (17)

Adult AIDS Serodiagnosis Cervix Uteri Comorbidity Creatinine Cyclooxygenase 2 Dinoprostone Female Gene Expression Regulation, Viral Haiti HIV Infections HIV Seropositivity Humans Inflammation Middle Aged Papillomavirus Infections RNA, Messenger

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