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BioMed Research International
Volume 2013, Article ID 519619, 10 pages
http://dx.doi.org/10.1155/2013/519619
Review Article

Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

1Molecular Biology and Viral Oncology, National Cancer Institute “Fondazione Pascale”, Cappella Cangiani, 80131 Naples, Italy
2Servizio Interaziendale di Epidemiologia, AUSL Reggio Emilia, 42121 Reggio Emilia, Italy

Received 7 October 2013; Accepted 10 November 2013

Academic Editor: Renato Franco

Copyright © 2013 Maria Lina Tornesello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cervical cancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV) genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1) increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2) integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3) molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervical cancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a) and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervical cancer.