The presence of aflatoxin B₁-FAPY adduct and human papilloma virus in cervical smears from cancer patients in Mexico

Abstract

The carcinogenic biomarker aflatoxin B₁-formamidopyrimidine 2,3-dihydro-2-(N-formyl)-2′,5′,6′-triamino-4′-4′-oxy-N-pyrimidyl-3-hydroxy-AFB₁ called AFB₁-FAPY adduct, and Human Papilloma Virus (HPV) types 16 and 18 were quantified from DNA cervical scrapes from 40 women with cervical cancer (CC) and 14 healthy women as controls. The relationship between the AFB₁-FAPY adduct and HPV types 16 and 18 was determined. Competitive inhibitory indirect ELISA was validated with 94% inhibition to quantify the AFB₁-FAPY adducts in picograms per milligram of DNA (limit of detection = 0.1 pg/mg, and limit of quantification = 10 pg/mg), polymerase chain reaction and DNA sequencing to identify HPV types. The average concentration of AFB₁-FAPY adducts/mg DNA in the CC cases was 1025 pg, 1420 pg with HPV16 and 630 pg sharing HPV18 (p = 0.03). In comparison, healthy controls had ≤2.6 pg/mg DNA, a statistically significant difference (p = 0.00006). The presence of AFB₁-FAPY adduct increased six-fold the risk for CC between cases and controls, the odds ratio was 6.1 (95% CI = 1.4–25.4). There was a close relationship between the AFB₁-FAPY adducts and HPV16 in CC samples.

Keywords:

• AFB₁-FAPY adducts
• human papillomavirus
• HPV
• cervical cancer
• HPV16
• HPV18

Acknowledgements

We acknowledge the following institutions and individuals for their support: the Institute of Biology at UNAM (Instituto de Biología, Universidad Nacional Autónoma de México) for the infrastructure, laboratories and material they provided; the Army School of Medicine for the laboratories and material they provided; Joel Villavicencio, Jorge López, Julio César Montero and Alfredo Wong, IBUNAM, for their computing support; and Georgina Ortega Leite and Gerardo Arévalo, IBUNAM, for their bibliographic support.