Persistent infection with high-risk human papillomavirus (HPV) is the main risk factor in the development of cervical cancer (CC). Near than 200 HPV types have been described in which at least 40 are sexually transmitted infecting the genital mucosa. Based on their oncogenic potential, these can be classified as oncogenic "high risk" and "low risk" . HPVs are specific to the infection of cells of the basal stratum of squamous epithelial tissue. The introduction of virions into the cell is initiated by the interaction of the L1 protein with glycoproteins on the cell surface. It has also been associated with integrin alpha-6 in the entry of the virus into the cell. Once it interacts with the cell, HPV enter the cell through clathrin-dependent endocytosis . HPV infection is the most common sexually transmitted disease in the human population but most HPV infections are cleared by the immune system within two years. The main risk factors for HPV infection are the early sexual initiation, multiple sexual partners, multiparity and immunosuppression . Interestingly, HPV infection prevalence changes by geographical location. In North America, the prevalence is 13.8%, South America 14.3%, Europe, and Asia with 6.6% and 8.3% respectively while the regions with the highest prevalence are the African continent and Central America (including Mexico) with 22.9% and 20.5% respectively . HPV infections are more frequent in developing countries, although the exposure to risk factors for HPV infection is similar between developed and developing regions .
On the other hand, a recent study determined that maize contaminated with a mycotoxin, fumonisin B1 (FB1), derived from a filamentous fungus is associated with the transmission of the human immunodeficiency virus (HIV) in Sub-Saharan Africa. The authors in this study hypothesize a relationship between the consumption of maize contaminated with FB1 and the increase in HIV transmission, suggesting that maize contaminated with FB1 is an important factor in the HIV transmission. According to the statistical model used, eliminating the "maize factor" from Sub-Saharan Africa could reduce HIV transmission by 58% . Other studies associate FB1 consumption with an increase in esophageal cancer and hepatocarcinoma, in regions of South Africa, India and China where they have a high exposure to this mycotoxin . FB1 is the most toxicologically important and represents 70–80% of the total fumonisin found in nature, fumonisin B2 (FB2) represent 15 to 25% and fumonisin B3 (FB3) only represent 3–8%. Fumonisins B contain a linear skeleton of 20 carbons, with a chemical structure similar to the long chain of sphingolipid precursors. The novo synthesis of sphingolipids begins with serine palmitoyl-CoA complex and also of the hydrolysis of complex sphingolipids. The main enzyme in this synthesis process is the ceramide synthetase (CS). This enzyme is blocked by FB1 through competitive inhibition and increases sphinganine and sphingosine (precursors of sphingolipids) favoring virus infection. Finally, produces a state of cellular permeability . A detailed mechanism of interaction of FB1 with CS was described, briefly, the part of FB1 that has structural similarity to sphingoid bases may interact with the sphinganine binding site, while the negatively charged tricarboxylic acid groups may interact with the fatty acyl-CoA binding site . However, when the tricarboxylic acid groups are separated from the FB1 by hydrolysis, the resulting product (aminopentol, AP1 or HFB1) not only acts as an inhibitor, but also as a substrate for the CS; aminopentol is acylated by CS to form N-palmitoyl-AP1. This supports the suggestion that the aminopentol part of FB1 occupies the sphinganine space in the enzyme. N-palmitoyl-AP1 is an even more potent inhibitor of ceramide synthase and may therefore play a role in the toxicity of FB1 . The decrease of complex sphingolipids and the accumulation of sphingoid bases (sphinganine and sphingosine) alter the cellular functions and alters the balance of cell death and replication and thus contributes to carcinogenesis, even more important is the effect on cellular permeability that would potentially facilitate interaction with pathogens, such as viruses .
On the other hand, the methods used for maize processing influence the final concentration of FB1. For example, the main form to obtain the mass of maize, nixtamalization, that consists in cooking maize grains in an alkaline solution of calcium hydroxide (CaOH2), at a temperature close to the boiling point, reduces the concentration of FB1 in approximately 90% and the residual amount remains in its hydrolyzed form (HFB1), which is less potent in vitro than FB1 . However, when the process is incomplete and the pericarp is not adequately eliminated, 31% of FB1 remains in its original form . In Mexico, a study evaluated the consumption of tortillas (traditional food in Mexico, derived from maize) as a source of exposure to FB1 in humans. The consumption of maize was classified as high, medium, or low according to the consumption of tortillas. The urinary concentrations of FB1 were 3.5 times higher among women in the highest category of maize consumption compared to those in the lowest category. The authors concluded that the consumption of tortillas is directly related to the exposure of fumonisins . The maize and its derivatives (such as tortilla) are essential foods in the Mexican diet, so the exposure to FB1 is greater than other countries. In this sense represents potentially a public health problem in Mexico. This biological factor has not yet been explored as a risk factor for HPV infection. In the present preliminary study, it is postulated that exposure to FB1 favors HPV infection. The objective of the present preliminary study is to determine levels of FB1 in urine of women positive and negative to HPV infection, to establish a possible association and propose a new risk factor in HPV infection.