TY - JOUR
T1 - The effect of HIV and HPV coinfection on cervical COX-2 expression and systemic prostaglandin E 2 levels
AU - Fitzgerald, Daniel W.
AU - Bezak, Karl
AU - Ocheretina, Oksana
AU - Riviere, Cynthia
AU - Wright, Thomas C.
AU - Milne, Ginger L.
AU - Zhou, Xi Kathy
AU - Du, Baoheng
AU - Subbaramaiah, Kotha
AU - Byrt, Erin
AU - Goodwin, Matthew L.
AU - Rafii, Arash
AU - Dannenberg, Andrew J.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84862907776
U2 - 10.1158/1940-6207.CAPR-11-0496
DO - 10.1158/1940-6207.CAPR-11-0496
M3 - Article
C2 - 22135046
AN - SCOPUS:84862907776
SN - 1940-6207
VL - 5
SP - 34
EP - 40
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 1
ER -