scholarly journals Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2234
Author(s):  
Ena Pešut ◽  
Anamaria Đukić ◽  
Lucija Lulić ◽  
Josipa Skelin ◽  
Ivana Šimić ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Cell Cycle Control ◽  
Human Papillomaviruses ◽  
Causative Role ◽  
Dna Viruses ◽  
Viral Oncoproteins ◽  
Control Networks ◽  
Malignant Lesions ◽  
E6 And E7 ◽  
Regulation Of Cell Cycle

Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.

scholarly journals Whole Genomic Analysis and Comparison of Two Canine Papillomavirus Type 9 Strains in Malignant and Benign Skin Lesions

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 736
Author(s):  
Chia-Yu Chang ◽  
Nanako Yamashita-Kawanishi ◽  
Sonoka Tomizawa ◽  
I-Li Liu ◽  
Wei-Tao Chen ◽  
...  
Keyword(s):  
Animal Species ◽  
Reference Strain ◽  
Genomic Analysis ◽  
Skin Lesions ◽  
Human Papillomaviruses ◽  
Viral Oncoproteins ◽  
E2 Protein ◽  
Viral Plaque ◽  
Malignant Lesions ◽  
E6 And E7

Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are suggested as one of the risk factors for the development of squamous cell carcinomas (SCCs). In the present study, the full genomes of two CPV9 strains from recurrent SCCs of Dog 1 and skin viral papilloma (viral plaque) of Dog 2 were sequenced. Alignment of the two CPV9 sequences with the genome of the reference CPV9 strain (accession no. JF800656.1) derived from a solitary pigmented plaque was performed. Compared with the reference strain, a 27 bp in-frame insertion in the E1 gene was identified in both CPV9 strains in this study. In comparison with the CPV9 strains derived from benign lesions, the CPV9 from the SCCs of Dog 1 exhibited a 328 bp deletion at the 3′ end of the E2 and spacer sequence, which encoded a truncated deduced E2 protein and a chimeric E8^E2 protein. However, there was no difference in the mRNA expression levels of viral oncoproteins of E6 and E7 between the two CPV9 cases, suggesting that the oncogenesis of CPV9 for malignant transformation might be different from that of human papillomaviruses. The roles of E2 and E8^E2 deleted CPV9 in the oncogenesis of benign and malignant lesions should be further investigated.

Human papillomaviruses and associated malignancies.

1998 ◽  
Vol 16 (1) ◽  
pp. 330-337 ◽  
Author(s):  
R M Alani ◽  
K Münger
Keyword(s):  
Current Knowledge ◽  
Cellular Transformation ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Cellular Growth ◽  
Current Understanding ◽  
In Vivo Studies ◽  
E6 And E7

The human papillomaviruses (HPVS) are small DNA tumor viruses that infect epithelial cells and induce proliferative lesions. Substantial epidemiologic data along with in vitro and in vivo studies have led to the implication of particular HPVs with the development of epithelial malignancies. Greater than 90% of all cervical carcinomas are positive for HPV infection. Most of these lesions are caused by infection with mucosal-associated high-risk HPV subtypes. Much work has been undertaken in basic science laboratories to determine the molecular basis for HPV-associated malignancies. Although many significant advances have been made in understanding the biologic properties of these viruses using in vitro analyses, the field has been greatly hindered until recently by the inability to propagate the virus in culture. In this review, we discuss the basic biologic properties of HPVs and the current understanding of the mechanisms of cellular transformation by malignancy-associated viral subtypes. We place particular emphasis on discussion of the HPV oncogenes, E6 and E7. We also discuss premalignant and malignant disorders of squamous and mucosal epithelia, which have been associated with HPV infections, and the current understanding of the mechanism of HPV-associated carcinogenesis in these settings. We focus these discussions on cervical carcinogenesis and briefly review the particulars regarding HPV-associated malignancies in normal and immunocompromised hosts. We end with a discussion of potential targeted molecular therapies for HPV-associated malignancies that may result from the current knowledge of HPV-related cellular growth dysregulation and carcinogenesis.

scholarly journals Origin and evolution of papillomavirus (onco)genes and genomes

2019 ◽  
Vol 374 (1773) ◽  
pp. 20180303 ◽  
Author(s):  
Anouk Willemsen ◽  
Ignacio G. Bravo
Keyword(s):  
Common Ancestor ◽  
Current Knowledge ◽  
Phylogenetic Analyses ◽  
Genotypic Diversity ◽  
Human Papillomaviruses ◽  
Recent Common Ancestor ◽  
Origin And Evolution ◽  
Most Recent Common Ancestor ◽  
E6 And E7 ◽  
E7 Proteins

Papillomaviruses (PVs) are ancient viruses infecting vertebrates, from fishes to mammals. Although the genomes of PVs are small and show conserved synteny, PVs display large genotypic diversity and ample variation in the phenotypic presentation of the infection. Most PV genomes contain two small early genes E6 and E7 . In a bunch of closely related human papillomaviruses (HPVs), the E6 and E7 proteins provide the viruses with oncogenic potential. The recent discoveries of PVs without E6 and E7 in different fish species place a new root on the PV tree, and suggest that ancestral PVs consisted of the minimal PV backbone E1-E2-L2-L1 . Bayesian phylogenetic analyses date the most recent common ancestor of the PV backbone to 424 million years ago (Ma). Common ancestry tests on extant E6 and E7 genes indicate that they share a common ancestor dating back to at least 184 Ma. In AlphaPVs infecting Old World monkeys and apes, the appearance of the E5 oncogene 53–58 Ma concurred with (i) a significant increase in substitution rate, (ii) a basal radiation and (iii) key gain of functions in E6 and E7. This series of events was instrumental to construct the extant phenotype of oncogenic HPVs. Our results assemble the current knowledge on PV diversity and present an ancient evolutionary timeline punctuated by evolutionary innovations in the history of this successful viral family. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.

Human Papillomaviruses, Tumour Suppressor Genes and Cervical Cancer

1993 ◽  
Vol 4 (3) ◽  
pp. 128-134 ◽  
Author(s):  
G J Inman ◽  
I D Cook ◽  
R K W Lau
Keyword(s):  
Current Knowledge ◽  
Squamous Carcinoma ◽  
Molecular Study ◽  
Suppressor Gene ◽  
Hpv Infection ◽  
Tumour Suppressor Gene ◽  
Human Papillomaviruses ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
E6 And E7

There is now a considerable body of evidence that links HPV infection with anogenital squamous carcinoma, particularly for specific ‘high risk’ HPV types (HPV16 and 18) and invasive carcinoma of the cervix. Recent advances in the molecular study of these viruses have elucidated some potential mechanisms by which they may contribute to the development of these diseases. In this review we concentrate on the interactions of 2 of the HPV encoded proteins, E6 and E7, with cellular tumour suppressor gene products. We provide a model of how these interactions may be important in tumourigenesis and draw together current knowledge of this exciting and rapidly evolving field.

scholarly journals Development and validation of a multiplex qPCR assay for detection and relative quantification of HPV16 and HPV18 E6 and E7 oncogenes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexia Bordigoni ◽  
Anne Motte ◽  
Hervé Tissot-Dupont ◽  
Philippe Colson ◽  
Christelle Desnues
Keyword(s):  
Limit Of Detection ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Papillomaviruses ◽  
Molecular Techniques ◽  
Clinical Samples ◽  
Gene Encoding ◽  
Hpv Dna ◽  
E6 And E7 ◽  
High Risk Hpv ◽  
Development And Validation

AbstractHuman papillomaviruses (HPV) play a key role in promoting human anogenital cancers. Current high-risk HPV screening or diagnosis tests involve cytological or molecular techniques mostly based on qualitative HPV DNA detection. Here, we describe the development of a rapid quantitative polymerase chain reaction (qPCR) detection test of HPV16 and HPV18 oncogenes (E6 and E7) normalized on human gene encoding GAPDH. Optimized qPCR parameters were defined, and analytical specificities were validated. The limit of detection was 101 for all genes tested. Assay performances were evaluated on clinical samples (n = 96). Concordance between the Xpert HPV assay and the triplex assay developed here was 93.44% for HPV16 and 73.58% for HPV18. HPV co-infections were detected in 15 samples. The systems developed in the present study can be used in complement to traditional HPV tests for specifically validating the presence of HPV16 and/or HPV18. It can also be used for the follow-up of patients with confirmed infection and at risk of developing lesions, through the quantification of E6 and E7 oncogene expression (mRNA) normalized on the GAPDH expression levels.

scholarly journals Pathogenic Role of Immune Evasion and Integration of Human Papillomavirus in Oropharyngeal Cancer

2021 ◽  
Vol 9 (5) ◽  
pp. 891
Author(s):  
Takashi Hatano ◽  
Daisuke Sano ◽  
Hideaki Takahashi ◽  
Nobuhiko Oridate
Keyword(s):  
Human Papillomavirus ◽  
Immune Evasion ◽  
Oropharyngeal Cancer ◽  
Current Knowledge ◽  
Immune Evasion Mechanism ◽  
Cell Cycle Activation ◽  
Genome Integration ◽  
Integration Mechanisms ◽  
E6 And E7

The incidence of oropharyngeal cancer (OPC) is increasing remarkably among all head and neck cancers, mainly due to its association with the human papillomavirus (HPV). Most HPVs are eliminated by the host’s immune system; however, because HPV has developed an effective immune evasion mechanism to complete its replication cycle, a small number of HPVs are not eliminated, leading to persistent infection. Moreover, during the oncogenic process, the extrachromosomal HPV genome often becomes integrated into the host genome. Integration involves the induction and high expression of E6 and E7, leading to cell cycle activation and increased genomic instability in the host. Therefore, integration is an important event in oncogenesis, although the associated mechanism remains unclear, especially in HPV-OPC. In this review, we summarize the current knowledge on HPV-mediated carcinogenesis, with special emphasis on immune evasion and integration mechanisms, which are crucial for oncogenesis.

scholarly journals Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6047
Author(s):  
Mattias F. Lindberg ◽  
Laurent Meijer
Keyword(s):  
Tyrosine Phosphorylation ◽  
Human Disease ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Viral Infections ◽  
Current Knowledge ◽  
Lymphoblastic Leukemia ◽  
Cell Cycle Control ◽  
Megakaryoblastic Leukemia ◽  
Dual Specificity

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.

The biological properties of E6 and E7 oncoproteins from human papillomaviruses

Virus Genes ◽  
2009 ◽  
Vol 40 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Raffaella Ghittoni ◽  
Rosita Accardi ◽  
Uzma Hasan ◽  
Tarik Gheit ◽  
Bakary Sylla ◽  
...  
Keyword(s):  
Biological Properties ◽  
Human Papillomaviruses ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

Sclerosing Angiomatoid Nodular Transformation of the Spleen

2013 ◽  
Vol 137 (9) ◽  
pp. 1309-1312 ◽  
Author(s):  
Dinesh Pradhan ◽  
Sambit K. Mohanty
Keyword(s):  
Current Knowledge ◽  
Benign Lesion ◽  
Good Prognosis ◽  
Unknown Etiology ◽  
Age Group ◽  
Imaging Findings ◽  
Effective Technique ◽  
Sclerosing Angiomatoid Nodular Transformation ◽  
Malignant Lesions ◽  
Mitotic Figures

Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen is a rare benign lesion of the spleen with unknown etiology. SANT is classically considered to be a female-predominant disease, with most of the patients in the 30- to 60-year age group. Most lesions are found incidentally on imaging. Although SANT has specific imaging findings, the differential diagnosis from other splenic tumors or malignant lesions is very difficult. Histopathologically, these tumors reveal multiple confluent angiomatoid nodules; these nodules are surrounded by concentric collagen fibers exhibiting an inflammatory and myofibroblastic response and are accompanied by numerous erythrocytes and siderophages. The nodules are populated by endothelial cells, phenotypically recapitulating normal splenic vasculature, such as sinusoids, capillaries, and small veins. Nuclear atypia is minimal, mitotic figures are extremely rare, and necrosis is consistently absent. This lesion has a unique immunohistochemical profile characterized by CD34−CD31+CD8+ sinusoids, CD34+CD31+CD8− capillaries, and CD34−CD31+CD8− small veins. CD68 is positive in macrophages. Splenectomy is a useful and effective technique for the management of SANT. SANT patients have a good prognosis, with no recurrence after splenectomy. In this review, we discuss the current knowledge of SANT of the spleen and its clinical relevance.

scholarly journals Mucosal Human Papillomaviruses Encode Four Different E5 Proteins Whose Chemistry and Phylogeny Correlate with Malignant or Benign Growth

2004 ◽  
Vol 78 (24) ◽  
pp. 13613-13626 ◽  
Author(s):  
Ignacio G. Bravo ◽  
Ángel Alonso
Keyword(s):  
Human Papillomaviruses ◽  
Structural Proteins ◽  
Phylogenetic Study ◽  
Protein Divergence ◽  
Early Proteins ◽  
Differential Involvement ◽  
E6 And E7 ◽  
Different Characteristics ◽  
L1 And L2 ◽  
Transformation Processes

ABSTRACT We performed a phylogenetic study of the E2-L2 region of human mucosal papillomaviruses (PVs) and of the proteins therein encoded. Hitherto, proteins codified in this region were known as E5 proteins. We show that many of these proteins could be spurious translations, according to phylogenetic and chemical coherence criteria between similar protein sequences. We show that there are four separate families of E5 proteins, with different characteristics of phylogeny, chemistry, and rate of evolution. For the sake of clarity, we propose a change in the present nomenclature. E5α is present in groups A5, A6, A7, A9, and A11, PVs highly associated with malignant carcinomas of the cervix and penis. E5β is present in groups A2, A3, A4, and A12, i.e., viruses associated with certain warts. E5γ is present in group A10, and E5δ is encoded in groups A1, A8, and A10, which are associated with benign transformations. The phylogenetic relationships between mucosal human PVs are the same when considering the oncoproteins E6 and E7 and the E5 proteins and differ from the phylogeny estimated for the structural proteins L1 and L2. Besides, the protein divergence rate is higher in early proteins than in late proteins, increasing in the order L1 < L2 < E6 ≈ E7 < E5. Moreover, the same proteins have diverged more rapidly in viruses associated with malignant transformations than in viruses associated with benign transformations. The E5 proteins display, therefore, evolutionary characteristics similar to those of the E6 and E7 oncoproteins. This could reflect a differential involvement of the E5 types in the transformation processes.

Sign in / Sign up

Export Citation Format

Share Document