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Human Papillomavirus and Cancers: Advances and Future Prospects
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Human Papillomavirus and Cancers: Advances and Future Prospects

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: closed (31 August 2024) | Viewed by 7783

Special Issue Editors

Dr. Christine Kottaridi

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Guest Editor
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: oncogenic viruses; virus-host interactions; viral genome editing; viral evolution
Special Issues, Collections and Topics in MDPI journals
Dr. Dimitris Tsakogiannis

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Guest Editor
Research Center, Hellenic Anticancer Institute, Athens, Greece
Interests: molecular virology; oncogenic viruses; HPV; biomarkers; virus–host interactions; viral evolution
Special Issues, Collections and Topics in MDPI journals
Dr. Zaharoula Kyriakopoulou

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Guest Editor
Department of Environment, School of Technology, University of Thessaly, Gaiopolis, 41500 Larissa, Greece
Interests: molecular virology; molecular epidemiology; viral molecular detection; HPV; enteroviruses; environmental virology

Special Issue Information

Dear Colleagues,

Human Papillomaviruses (HPVs) are non-enveloped, double–stranded circular DNA viruses that infect basal keratinocytes of mucosal and cutaneous epithelia. Persistent high-risk HPV infection is the etiologic agent of approximately all cervical cancer incidences and of a considerable part of various types of malignancies including vulvar, vaginal, anal, penile, oropharyngeal and skin cancers.  Although cytological testing (the Papanicolaou, Pap test), HPV screening and HPV vaccination programs have reduced the rates of cervical malignancy, it remains a major public health problem, globally.

HPVs have developed several molecular approaches in order to inhibit cell-cycle arrest and apoptosis.  The extensive expression of viral oncoproteins and the integration of viral DNA into the host chromosome are involved in chromosomal instability and the accumulation of DNA damage in the infected cells, thus leading to cancer development. Moreover, various epigenetic changes, including viral or host genes΄ methylation and miRNAs differential expression play an important role in host-viral interplay. The HPV tumorigenic capacity has also been associated with specific nucleotide and amino-acid substitutions, characterizing specific genotypes and variant lineages, that have been reported globally.  

The aim of this special issue is to better understand the molecular mechanisms that are implicated in HPV carcinogenicity. We welcome submissions of research articles and reviews focused on the following potential topics (but are not limited to): molecular mechanisms (e.g epigenetic mechanisms, viral integration events, viral oncoproteins deregulation), HPV genetic variability, biomarkers development, molecular epidemiology and new HPV detection and genotyping molecular assays in order to meet expert views, state of the art and recent advancements in the field of HPV,  in the present Special Issue of International Journal of Molecular Sciences. 

Dr. Christine Kottaridi
Dr. Dimitris Tsakogiannis
Dr. Zaharoula Kyriakopoulou
Guest Editors

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

  • α-HPV
  • β-ΗPV
  • γ-HPV
  • variability
  • epidemiology
  • oncogenic viruses
  • methylation
  • miRNA
  • biomarkers
  • molecular typing
  • carcinogenesis
  • cervical cancer
  • oropharyngeal cancer
  • skin cancer

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Published Papers (3 papers)

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Research

12 pages, 3939 KiB  
Article
Dysregulation of FURIN and Other Proprotein Convertase Genes in the Progression from HPV Infection to Cancer
by Gonzalo Izaguirre, Natalia Zirou and Craig Meyers
Int. J. Mol. Sci. 2025, 26(2), 461; https://doi.org/10.3390/ijms26020461 - 8 Jan 2025
Viewed by 668
Abstract
Productive infections of oncogenic human papillomaviruses (HPVs) are closely linked to the differentiation of host epithelial cells, a process that the virus manipulates to create conditions favorable to produce virion progeny. This viral interference involves altering the expression of numerous host genes. Among [...] Read more.
Productive infections of oncogenic human papillomaviruses (HPVs) are closely linked to the differentiation of host epithelial cells, a process that the virus manipulates to create conditions favorable to produce virion progeny. This viral interference involves altering the expression of numerous host genes. Among these, proprotein convertases (PCs) have emerged as potential oncogenes due to their central role in cellular functions. Using RT-qPCR, aberrant PC gene expression was detected across the progression from early HPV infection stages to cancer. These findings demonstrated a progressive disruption of normal PC expression profiles, with FURIN consistently downregulated and other PCs upregulated, transitioning from the episomal stage to neoplastic and carcinoma phenotypes. This pattern of dysregulation was distinct from the broader trends observed in a variety of cancer types through bioinformatic analysis of publicly available transcriptomic datasets, where FURIN expression was predominantly upregulated compared to other PCs. Further bioinformatic investigations revealed a correlation between PC gene expression and cancer phenotype diversity, suggesting a potential link between the loss of normal PC gene expression patterns and the progression of HPV infections toward malignancy. Full article
(This article belongs to the Special Issue Human Papillomavirus and Cancers: Advances and Future Prospects)
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17 pages, 1862 KiB  
Article
Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms
by Dariusz Jarych, Damian Mikulski, Miłosz Wilczyński, Jacek R. Wilczyński, Katarzyna D. Kania, Daria Haręża, Andrzej Malinowski, Ewelina Perdas, Mateusz Nowak and Edyta Paradowska
Int. J. Mol. Sci. 2024, 25(2), 762; https://doi.org/10.3390/ijms25020762 - 7 Jan 2024
Cited by 3 | Viewed by 2546
Abstract
This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of [...] Read more.
This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host–virus interactions. Full article
(This article belongs to the Special Issue Human Papillomavirus and Cancers: Advances and Future Prospects)
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11 pages, 1003 KiB  
Article
Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases
by Ioannis Zygouras, Danai Leventakou, Abraham Pouliakis, Styliana Panagiotou, Dimitris Tsakogiannis, Georgios Konstantopoulos, Eirini Logotheti, Menelaos Samaras, Zaharoula Kyriakopoulou, Apostolos Beloukas, Ioannis S. Pateras, Alexandros Delides, Amanda Psyrri, Ioannis G. Panayiotides, Minas Yiangou and Christine Kottaridi
Int. J. Mol. Sci. 2023, 24(19), 14593; https://doi.org/10.3390/ijms241914593 - 26 Sep 2023
Cited by 6 | Viewed by 3424
Abstract
Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established [...] Read more.
Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus–host interactions. Full article
(This article belongs to the Special Issue Human Papillomavirus and Cancers: Advances and Future Prospects)
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