Epigenetics of cervical cancer. An overview and therapeutic perspectives

Cervical cancer remains one of the greatest killers of women worldwide. According to Globocan 2000, it is estimated that in 2000 the numbers of patients diagnosed with and those who died from this disease were 470,606 and 233,372, respectively [1]. It is remarkable that these rates occur despite the fact that cervical cancer is a model for early detection due to its long and relatively well-known natural history, which offers an excellent opportunity for its detection before lesions become invasive [2].Cervical cancer is currently staged clinically according the International Federation of Gynecology and Obststrics (FIGO) guidelines. In terms of treatment, invasive disease can be divided into three main groups: 1) early stage going from microinvasive disease IA1, IA2 to macroscopic disease confined to cervix and measuring <4 cm, IB1; 2) locally advanced FIGO stages IB2-IVA, and 3) IVB and recurrent disease [3].The recommended treatment for IA1 patients is either a local procedure such as conization or total hysterectomy depending on the patient's desire to remain fertile, whereas for IA2 patients the recommended procedure is a radical one including pelvic lymphadenectomy. On average, 8% of cases shows positive pelvic lymph nodes. As many women at this disease stage deserve to preserve fertility, radical trachelectomy is becoming an option for these patients. The same can apply for IB1 patients. In early cases that are surgically treated, the presence in the surgical specimen of a combination of intermediate-risk factors (vascular and lymphatic permeation, tumor size >2 cm, and deep cervical stroma invasion) or high-risk factors (positive pelvic lymph nodes, parametrial infiltration, and positive surgical margins) dictates use of adjuvant radiation or chemoradiation respectively. As a group, the prognosis of early-stage cases is fairly good with 5-year survival exceeding 90% [4,5]Results of treatment for these patients are far from optimal. In this regard, treatment