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Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Published online by Cambridge University Press:  01 December 2021

G. Bletsa ,
F. Zagouri ,
G. D. Amoutzias ,
M. Nikolaidis ,
E. Zografos ,
P. Markoulatos  and
D. Tsakogiannis Open the ORCID record for D. Tsakogiannis [Opens in a new window]
G. Bletsa
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
F. Zagouri
Affiliation:
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
G. D. Amoutzias
Affiliation:
Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
M. Nikolaidis
Affiliation:
Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
E. Zografos
Affiliation:
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
P. Markoulatos
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
D. Tsakogiannis*
Affiliation:
Research Center, Hellenic Anticancer Institute, Athens, Greece
*
Author for correspondence: D. Tsakogiannis, E-mail: [email protected], [email protected]
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Abstract

Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6: Q14H, H78Y, L83V, Ε7: N29S, S63F, E2: H35Q, P219S, T310K, E5: I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

Keywords

Amino-acid mutationscervical cancerearly genesHPV16LCRmolecular biomarkersnucleotide variationsoncogenesoncogenicityoncoproteins
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e19
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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