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Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 9844

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Special Issue Editor

Prof. Dr. Subhasis B. Biswas

E-Mail Website
Guest Editor

Department of Medical and Molecular Sciences, College of Health Sciences, University of Delaware, Newark, DE 19716, USA
Interests: molecular biology; genetics; human papillomavirus family (HPV); cervical and oropharyngeal cancer; visual diseases

Special Issue Information

Dear Colleagues,

I am delighted to invite you to submit an article on HPV and oncogenesis to a Special Issue of The International Journal of Molecular Sciences.

Human papillomavirus (HPV), one of the world's oldest viruses, is today the most prolific oncogenic virus. For decades, HPV has been synonymous with cervical cancer morbidity and mortality in the world of medicine. However, because of research studies such as those you produce, our knowledge of the relationship between HPV and cancer now extends more deeply. For example, HPV has been linked with a variety of oropharyngeal cancers. At both molecular and biochemical levels, we have significantly advanced our understanding of the mechanisms of HPV-induced oncogenesis. This Special Issue of the International Journal of Molecular Sciences is designed to draw these developments together to provide clinicians, students, and researchers alike with a clear, comprehensive picture of the latest research in HPV and oncogenesis.

In this issue, we would like to include the following topics:

Genetic mechanisms of oncogenesis;
Functions of HPV genes and oncogenes;
Regulation of cellular tumor suppressor genes upon HPV infection;
HPV genomic integration;
Correlation of HPV subtypes to oncogenesis;
Identification of new HPV subtypes;
HPV susceptibility mechanisms;
Inter-individual and genetic variation in responses to HPV infection;
Significant epidemiological findings relating to HPV and cancer.

Given your significant contributions to the field of HPV and oncogenesis, we anticipate that your contributions would be particularly valuable to our audience. We welcome your expertise in the form of a research paper or review article.

Prof. Dr. Subhasis B. Biswas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

human papillomavirus (HPV)
oncogenesis
mechanism
diagnosis
classification
etiology
pathophysiology
biochemistry
genetics
molecular biology
epidemiology
cervical cancer
oropharyngeal cancer
oncology

Published Papers (5 papers)

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Research

Jump to: Review

11 pages, 817 KiB

Open AccessArticle

Ficus carica Latex Modulates Immunity-Linked Gene Expression in Human Papillomavirus Positive Cervical Cancer Cell Lines: Evidence from RNA Seq Transcriptome Analysis

by Muharrem Okan Cakir, Ugur Bilge, Declan Naughton and G. Hossein Ashrafi

Int. J. Mol. Sci. 2023, 24(17), 13646; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241713646 - 04 Sep 2023

Viewed by 1210

Abstract

Cervical carcinogenesis is the leading cause of cancer-related deaths in women, and the role of high-risk human papillomavirus (HR-HPV) as a possible risk factor in the development of this cancer is well recognized. Despite the availability of multi-therapeutic approaches, there is still major concern regarding the prevention of metastatic dissemination and excessive tissue injuries. Therefore, it is imperative to develop a safer and more efficient treatment modality. Ficus carica, a natural plant, has shown potential therapeutic properties through its fruit latex when applied to HPV-positive cervical cancer cell lines. However, the mechanisms of action of Ficus carica (fig) latex are not well understood. This study aims to provide a deeper insight into the biological activities of fig latex on human cervical cancer cell lines expressing high-risk HPV types 16 and 18. The data obtained from this study reveal that fig latex influences the expression of genes involved in “Class I MHC-mediated antigen presentation” as well as “Antigen processing: Ubiquitination and Proteasome degradation”. These genes play a crucial role in host immune surveillance and the resolution of infection. Notably, Western blot analysis corroborated these findings, demonstrating an increase in the expression of MHC class I in HeLa cells after fig latex treatment. Findings from this study suggest that fig latex may enhance T cell responses against oncogenic HPV, which could be beneficial for the clearance of early-stage cancer. Full article

(This article belongs to the Special Issue Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis)

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18 pages, 4073 KiB

Open AccessArticle

Sequence-Dependent Interaction of the Human Papillomavirus E2 Protein with the DNA Elements on Its DNA Replication Origin

by Gulden Yilmaz, Esther E. Biswas-Fiss and Subhasis B. Biswas

Int. J. Mol. Sci. 2023, 24(7), 6555; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076555 - 31 Mar 2023

Cited by 4 | Viewed by 1455

Abstract

The human papillomavirus (HPV) E2 protein is essential for regulating the initiation of viral DNA replication as well as the regulation of transcription of certain HPV-encoded genes. Its ability to recognize and bind to its four recognition sequences in the viral origin is a key step in the initiation of HPV DNA replication. Thus, understanding the mechanism of DNA binding by E2 protein and the unique roles played by individual DNA sequence elements of the replication origin is essential. We have purified the recombinant full-length HPV type 11 E2 protein. Quantitative DNA binding analysis indicated E2 protein bound all four DNA binding sites with reasonably high affinities but with distinct preferences. It bound its cognate binding sites 1, 2, and 4 with higher affinities, but bound binding site 3 with lower affinity. Analysis of binding to these sites unraveled multiple sequence elements that appeared to influence E2 binding affinity and target discrimination, including the sequence of spacer region, flanking sequences, and proximity of E2 binding sites. Thermodynamic analysis indicated hydrophobic interaction in the protein-DNA complex formation. Our studies indicate a large multi-protein complex formation on the HPV-origin DNA, likely due to reasonably high binding affinities as well as intrinsic oligomerization propensity of E2 dimers. Full article

(This article belongs to the Special Issue Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis)

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11 pages, 2504 KiB

Open AccessArticle

Differential Urinary Proteomic Analysis of High-Risk Cervical Intraepithelial Neoplasia

by Peter Bober, Soňa Tkáčiková, Ivan Talian, Peter Urdzík, Silvia Toporcerová and Ján Sabo

Int. J. Mol. Sci. 2023, 24(3), 2531; https://doi.org/10.3390/ijms24032531 - 28 Jan 2023

Cited by 1 | Viewed by 1909

Abstract

Human papillomavirus (HPV)-associated lesions and malignancies exhibit alterations in the composition and functionality of the extracellular matrix (ECM) that represent the complex molecular pathways present between infection and disease. A total of 20 urine samples were used, including from 10 patients with cervical intraepithelial neoplasia grade 3 (CIN3) and 10 healthy controls to perform the label-free quantitative analysis using the nano-HPLC and ESI-MS ion trap mass analyzer and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS) fast screening. Among 476 identified/quantified proteins, 48 were significantly changed (log₂-fold change ≥1.0 or ≤−1.0, −log10 (bbinominal, p-value ≥ 1.3), of which were 40 proteins (down-regulated) and 8 proteins (up-regulated) in CIN3, in comparison to healthy controls. The biological function and key pathway enrichment of the gene set using gen set enrichment analysis (GSEA) were analyzed. The ECM-receptor interaction pathway (NES = −1.64, p = 0.026) was down-regulated by 13 proteins (HSPG2, COL6A1, COL6A3, SPP1, THBS1, TNC, DAG1, FN1, COMP, GP6, VTN, SDC1, and CD44; log₂ FC range from −0.03 to −1.48) for the CIN3 group in the KEGG database. The MALDI-TOF/MS screening showed the difference of protein profiles between the control and CIN3 groups, i.e., using the scatter plot with a well-separated shape, as well as effectively distinguishing both groups (control and CIN3) using genetic algorithms (GA) with cross-validation (51.56%) and recognition capability (95.0%). Decreased levels of ECM-receptor interaction proteins may cause disturbances in the interactions of cells with the ECM and play an important role in the development and progression of cervical cancer. Full article

(This article belongs to the Special Issue Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis)

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Review

Jump to: Research

21 pages, 853 KiB

Open AccessReview

Human Papillomavirus Infection in Penile Cancer: Multidimensional Mechanisms and Vaccine Strategies

by Lichao Wei, Kangbo Huang, Hui Han and Ran-yi Liu

Int. J. Mol. Sci. 2023, 24(23), 16808; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316808 - 27 Nov 2023

Viewed by 1309

Abstract

Penile cancer (PC) is a rare male malignant tumor, with early lymph node metastasis and poor prognosis. Human papillomavirus (HPV) plays a key role in the carcinogenesis of PC. This review aims to summarize the association between HPV infection and PC in terms of virus–host genome integration patterns (the disrupted regions in the HPV and PC genome), genetic alterations, and epigenetic regulation (methylation and microRNA modification) occurring in HPV and PC DNA, as well as tumor immune microenvironment reprogramming. In addition, the potential of HPV vaccination strategies for PC prevention and treatment is discussed. Understanding of the HPV-related multidimensional mechanisms and the application of HPV vaccines will promote rational and novel management of PC. Full article

(This article belongs to the Special Issue Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis)

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16 pages, 4759 KiB

Open AccessReview

Protein–DNA Interactions Regulate Human Papillomavirus DNA Replication, Transcription, and Oncogenesis

by Roxanne Evande, Anshul Rana, Esther E. Biswas-Fiss and Subhasis B. Biswas

Int. J. Mol. Sci. 2023, 24(10), 8493; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108493 - 09 May 2023

Cited by 1 | Viewed by 3106

Abstract

Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being “high-risk” types that have been clinically linked to cervical and other types of cancer. “Low-risk” types of HPV cause less severe conditions, such as genital warts. Over the past few decades, numerous studies have shed light on how HPV induces carcinogenesis. The HPV genome is a circular double-stranded DNA molecule that is approximately 8 kilobases in size. Replication of this genome is strictly regulated and requires two virus-encoded proteins, E1 and E2. E1 is a DNA helicase that is necessary for replisome assembly and replication of the HPV genome. On the other hand, E2 is responsible for initiating DNA replication and regulating the transcription of HPV-encoded genes, most importantly the E6 and E7 oncogenes. This article explores the genetic characteristics of high-risk HPV types, the roles of HPV-encoded proteins in HPV DNA replication, the regulation of transcription of E6 and E7 oncogenes, and the development of oncogenesis. Full article

(This article belongs to the Special Issue Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis)

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