Infection with oncogenic Papillomavirus genotypes is considered a major risk factor for the development of cervical cancer; nonetheless only a small proportion of the infected patients actually develop malignancies. The specific identification of high grade lesions is pivotal to increase the effectiveness of the cervical cancer screening. In the present study promising candidate molecular biomarkers based on the Human Papillomavirus (HPV) genomes were assessed in a cross-sectional cohort formed by samples singly infected with the most prevalent oncogenic genotypes 16, 18, 31 and 45. The candidate markers under investigation were the DNA viral load (VL), viral CpG methylation and viral integration. For the HPV16 samples, sequence variation within the regulatory region was also assessed. The viral integration was evaluated in a smaller longitudinal set. The results obtained showed that the DNA VL was lowest in subclinical lesions. The viral methylation was highest in severe dysplastic samples and differences in methylation profiles were observed between HPV species. The viral integration displayed a significant depletion of HPV16 episomal forms in cancerous lesions and the presence of viral integrants in all cytology grades. The analysis of the HPV16 variants identified eight novel polymorphisms and mutations profiles were specifically recovered in high grade cervical lesions. It was concluded that the viral genome modifications allowed the prediction of the cervical lesions. The combination of the molecular markers might allow a higher clinical specificity in the identification of cervical cancer precursor lesions.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626840 |
| Date | January 2014 |
| Creators | Marongiu, L. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1427690/ |
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