title: The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E2 levels.
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.
authors.affiliation: Division of Infectious Diseases, Center for Global Health, Weill Cornell Medical College, 440 East 69 Street, New York, NY, USA. dfitzgerald@gheskio.org
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Fitzgerald
authors.forename: Karl
authors.initials: K
authors.lastname: Bezak
authors.forename: Oksana
authors.initials: O
authors.lastname: Ocheretina
authors.forename: Cynthia
authors.initials: C
authors.lastname: Riviere
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wright
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.forename: Baoheng
authors.initials: B
authors.lastname: Du
authors.forename: Kotha
authors.initials: K
authors.lastname: Subbaramaiah
authors.forename: Erin
authors.initials: E
authors.lastname: Byrt
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Goodwin
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
mesh_terms: D015492:AIDS Serodiagnosis / Q000379:methods; D000328:Adult; D002584:Cervix Uteri / Q000201:enzymology / Q000821:virology*; D015897:Comorbidity; D003404:Creatinine / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000150:complications* / Q000378:metabolism; D006679:HIV Seropositivity; D006205:Haiti; D006801:Humans; D007249:Inflammation; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003404:Creatinine; D051546:Cyclooxygenase 2; D015232:Dinoprostone