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The role of human papillomaviruses in cancer progression

Pinar Tulay, Nedime Serakinci
Department of Medical Genetics, Faculty of Medicine, Near East University, 999058 Nicosia, Cyprus.
Correspondence to: Dr. Nedime Serakinci, Department of Medical Genetics, Faculty of Medicine, Near East University, 999058 Nicosia, Cyprus.
E-mail: nedimeserakinci@gmail.com

A B S T R AC T
The importance of human papillomavirus (HPV) infection and its role in the progress of cancer have been widely evaluated. The
understanding of HPV association with certain cancers, such as cervical cancer, is very well established. A big step forward in the
prevention of HPV associated cancers with the use of early detection by screening strategies has also been taken. In the last decade,
development of HPV vaccination has reduced the number of cases in HPV infections and infection induced cancers. In this report,
we review the HPV pathogenesis and highlight the mechanism of HPV involvement in cancer development.

Key words: Human papillomavirus; cancer; immune response; human papillomavirus vaccine

INTRODUCTION cutaneous pathology. The HPVs can be further subdivided
according to the epidemiological classification as ones
Human papillomavirus (HPV) is considered to be one of the with low, intermediate and high risk oncogenic potentials
viral infections associated with cancers and other diseases depending on the viruses’ ability to promote the proliferation
worldwide. HPVs are non-enveloped viruses with double of infected cells and lead to malignant transformations. [1,11]
stranded circular DNA. [1,2] The genome of papillomavirus The low risk HPVs including HPV6, 11, 42, 43 and 44
constitutes three segments; early, late and genomic regions. may cause condylomas and benign cervical lesions that do
The early region with E1, E2, E4-E8 forms half of the HPV not form malignancies. [1,4,12,13] The intermediate oncogenic
genome. The early fragments function at different stages, risk HPVs involves HPV31, 33, 35, 51 and 52 and there is
in such both E1 and E2 is involved in the regulation of still an ongoing debate whether the intermediate oncogenic
DNA replication, E2 in transcription (E2), E5, E6 and E7 risk HPVs cause malignant transformation as much as the
in cell transformation [Table 1]. The late region (L) with high risk HPV types. [2,14] High oncogenic potential HPVs
L1 and L2 forms 40% of the genome and the genomic include HPV16, 18, 45 and 56 and these HPVs mostly
regulatory region forms the rest of the genome. The late cause neoplastic transformations. [2,4,14] Unlike alpha-
[3]
region of the genome involves the structural proteins of the HPVs, most of the beta- and gamma-HPVs results in
virion [Table 1]. [4] asymptomatic infections in immune-competent individuals
and these viruses adapt to their host and complete the life-
HPVs are characterised according to their tissue tropism and cycle without causing any apparent diseases. [8,15-17]
they are subdivided into five main genera (Alpha-, beta-,
gamma-, nu- and mu-papillomaviruses) depending on the Although the molecular defects caused by HPV
infection leads to malignant transformation, it is not
DNA sequences, HPV life cycle characteristics and disease well established how they predispose to disease and
associations. [5-8] Alpha-HPVs infect mucosal tissues, whether keratinocyte [18,19] or the immune system is being
whereas beta-, gamma-, nu- and mu-papillomaviruses compromised. [20,21] Therefore, although mainly the high
infects cutaneous sites causing cutaneous lesions in risk HPV types cause malignant transformation and the
humans. [9,10] However, as in recent years the number of low risks do no, it is possible that the low-risk viruses
HPV genotypes identified in healthy skin is increased, it
is difficult to assign the cutaneous HPV types with a given
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How to cite this article: Tulay P, Serakinci N. The role of human
papillomaviruses in cancer progression. J Cancer Metasta Treat
DOI: 2016;2:201-13.
10.20517/2394-4722.2015.67
Received: 31-08-2015; Accepted: 17-03-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 201