Proteomics Strategies to Analyze HPV-Transformed Cells: Relevance to Cervical Cancer

Fabio Di Domenico; Federico De Marco; Marzia Perluigi


Expert Rev Proteomics. 2013;10(5):461-472. 

In This Article

Expert Commentary

Cervical cancer represents the second most frequent cancer type among women worldwide and HPV infection is the most-well recognized etiological factors. Although most cases of HPV infections are clinically benign, in a small percentage (3–10%) of women the host immune response fails to clear the infection. These women become 'HPV-positive' and should undergo clinical screening to assess the risk for developing cervical cancer. The possibility to discriminate which lesion (dysplasia) is at a high risk to progress to cancer with those spontaneously regressing requires intensive screening programs to search for the candidate genes/proteins that play a role in progression of this disease. Proteomics platforms represent the most powerful strategy to identify putative tumor markers. A number of studies have been performed either on cell culture models, in relation to expression of specific oncogenes (mostly E6 and E7), and on human biopsies and ThinPrep specimens. By combining in vitro and in vivo data results (Figure 3) it is evident that viral oncogenes selectively interact with a subset of intracellular proteins regulating apoptosis, cell growth and differentiation and cell transformation. Among these, the unique proteins identified in common in cellular model and human tissues are ANXs and HSPs. Interestingly, both these proteins are target of oxidative damage thus suggesting that the oxidative modifications may affect their function. Recent studies suggest that ANX2 might be linked to carcinogenesis through its implication in the invasion and neovascularization processes and that the protein is regulated by the cellular redox status. Different members of HSP family have been found upregulated in invasive cervical tissues suggesting a protective mechanism against cancer development. It is likely that overexpression of HSPs is involved in cervical carcinogenesis process and possibly used as a prognostic tool.

Nevertheless, non-overlapping proteins have been identified by different proteomics approaches in different cell and tissue samples at different stages of progression and irreversible infection. Thus, taken as a whole, the altered expression could be explained with a manner of cell-cell interaction/host-viral interaction that represents a snapshot of the actual condition of the lesion before and after progression to cervical cancer.

Further proteomics studies are needed to get a more detailed characterization of different phases of tumor progression (CINs) which is mandatory to support diagnosis and eventually to set therapeutic interventions.