Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix

Cervical cancer (CC) is the second most prevalent neoplasia in women worldwide and the fifth cause of death by cancer in this population, posing a significant public health problem [1-3]. The incidence of CC and its precursor stages is high mainly in developing countries [4]. In 2008 an incidence of 15.8 and a mortality of 8.2 for every 100,000 women was estimated. Around 529,000 new cases are detected every year, with nearly half of these cases dying [5].The pathogenesis of CC begins as a slow process that interrupts the normal differentiation of the cervical squamous epithelium, thereby producing changes in its structure and physiology [6]. It initially presents through precursory lesions that evolve slowly and progressively, which can then advance to slight, moderate, and severe stages of dysplasia. CC may evolve into cancer in situ, which is limited to the epithelial surface, and/or into invasive cancer, in which case the involvement goes beyond the basement membrane [7]. Therefore, one of the characteristic factors of CC is its defined clinical stages, which are associated with the different evolutionary stages that lead to the development of the carcinogenesis [8].It has been firmly established, both biologically and epidemiologically, that the main cause of CC is due to a persistent infection of high-risk human papillomavirus (HPV) types, which are present in 99.7% of CC cases [9]. Nevertheless, the presence of a persistent high-risk HPV infection risk is not sufficient to immortalize and transform the epithelial cells of the host; it has been confirmed that the presence of genetic and epigenetic alterations are needed for the development of carcinogenesis. As a result, these factors taken together may alter the control of the cell cycle, causing the host cell to acquire an immortal phenotype and ultimately progress towards a malignant and invasive phenotype [10].HPV is a small, non-enveloped virus belonging to the Papillomaviridae family of viruses [11]. It