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Cervical cancer is the third most common cancer among women worldwide and is responsible for 275.000 deaths each year. The development of cervical cancer has been linked to cell cycle disturbances caused by persistent expression of high- risk HPV oncoproteins (E5, E6 and E7), which modulate the expression of host genes and cellular microRNAs. An estimated 5 million women throughout the world are currently infected by HPV and several of them will develop invasive cervical cancer. Despite failures in conventional screening tests, approved therapies have no direct effect on HPV infection. In view of this, effective therapy for cervical cancer is still urgently needed, particularly in developing countries where more than 85% of fatal cases occur. In this paper we review the current molecular targeted therapies which are being explored and may have a significant impact on the treatment of HPV- related cervical dysplasia and carcinoma.

Background: The objective of this study was to analyze the gene expression profile of the proinflammatory interleukins, (IL-1β and IL-18) in patients with premalignant lesions and cervical cancer. Methods: Total IL-1β and IL-18 mRNA was quantified by qPCR to obtain the expression data in cervical tissues. A total of 74 cervical biopsies were obtained from women undergoing a colposcopy. The samples were divided into: normal (19), low level lesions (LSIL) or NIC I (17), high level lesions (HSIL) or CIN II and CIN III (29) and cancer (9). The normal cervical tissue samples were included as controls. The OR and 95% CI were calculated for the determination of the risk of progression between each type of lesion and cancer using logistic regression. Results: The results showed that an increase in the risk of progression of pre-neoplastic lesions to cancer was between 2.5 and 2.08 times higher in women with lower IL-1β and IL-18 expression, respectively. Conclusions: This study provided evidence that IL-1β and IL-18 are potential biomarkers that can be explored in further studies for monitoring the evolution of pre-neoplastic lesions and avoiding overtreatment or undertreatment of the patients.

A number of recent studies have catalogued global gene expression patterns in a panel of normal, tumoral cervical tissues so that potential biomarkers can be identified. The qPCR has been one of the most widely used technologies for detecting these potential biomarkers. However, few studies have investigated a correct strategy for the normalization of data in qPCR assays for cervical tissues. The aim of this study was to validate reference genes in cervical tissues to ensure accurate quantification of mRNA and miRNA levels in cervical carcinogenesis. For this purpose, some issues for obtaining reliable qPCR data were evaluated such as the following: geNorm analysis with a set of samples which meet all of the cervical tissue conditions (Normal + CIN1 + CIN2 + CIN3 + Cancer); the use of individual Ct values versus pooled Ct values; and the use of a single (or multiple) reference genes to quantify mRNA and miRNA expression levels. Two different data sets were put on the geNorm to assess the expression stability of the candidate reference genes: the first dataset comprised the quantities of the individual Ct values; and the second dataset comprised the quantities of the pooled Ct values. Moreover, in this study, all the candidate reference genes were analyzed as a single “normalizer”. The normalization strategies were assessed by measuring p16INK4a and miR-203 transcripts in qPCR assays. We found that the use of pooled Ct values, can lead to a misinterpretation of the results, which suggests that the maintenance of inter-individual variability is a key factor in ensuring the reliability of the qPCR data. In addition, it should be stressed that a proper validation of the suitability of the reference genes is required for each experimental setting, since the indiscriminate use of a reference gene can also lead to discrepant results.

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