Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.

Abstract

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.

Foodborne toxin Aflatoxin B 1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

“…Afl atoxin B 1 (AFB 1 ) is the most toxic naturally-occurring mycotoxins to humans that poses urgent challenges for food saftey and public health [2] . AFB 1 is also a potent carcinogen contributing to liver, kidney, lung, cervical, and colorectal cancers [3][4][5][6][7] . Although AFB 1 is metabolized by liver microsomal enzyme, residual AFB 1 is excreted by the kidney that results in damages of glomerular podocytes and the anti-oxidant and anti-infl ammatory defense system via induction of reactive oxygen species (ROS) [8][9][10][11] .…”

Environmental Pollutants, Mucosal Barriers, and Pathogen Susceptibility; The Case for Aflatoxin B1 as a Risk Factor for HIV Transmission and Pathogenesis

“…AFB 1 is primarily studied as a potent hepatocellular carcinogen, however it is also linked to negative health endpoints in individuals with one of several viral infections. It leads to synergistic development of hepatocellular carcinoma, morbidity, and death during hepatitis B virus and/or hepatitis C virus co-infection, increases influenza viral replication, and is associated with oncogenic human papilloma virus [12][13][14]. Most importantly, AFB 1 exposure is correlated with higher HIV blood plasma viral load and is being investigated as a risk factor for HIV progression [15,16].…”