Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 13011

Special Issue Editor


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Guest Editor
Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, Universitatii St. No. 16, 700115 Iasi, Romania
Interests: HPV; polyomaviruses; HBV; EBV

Special Issue Information

Dear Colleagues,

Tumors caused by viruses (e.g., cervical cancer, skin cancer, head and neck cancers, liver cancer, kidney cancer) are following the global trend of increasing incidence of cancers. However, the viral origin also leads to some advantages, such as the availability of screening (HPV), personalized targeted therapy (MCV), and prevention by vaccination (HBV, HPV).

In this Special Issue, we would like to publish research articles regarding the most recent clinically validated and sensitive biomarkers (e.g., ctDNA) of the known oncogenic viruses (e.g., HPV, polyomaviruses, HBV, HCV, EBV), and their role for early tumor detection, prognosis, evolution, recurrence, and feasibility to be used as a therapy monitoring tool. Technical harmonization of the assays used for biomarkers detection is very important for testing the characteristics of these assays and for comparative studies.

I would like to invite colleagues investigating any oncogenic viruses within the areas of microbiology, virology, molecular biology, detection, public health, and vaccine development to submit their manuscripts to this Special Issue, in the form of original research and reviews.

Dr. Ramona Gabriela Ursu
Guest Editor

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Keywords

  • oncogenic viruses
  • specific biomarkers
  • early detection
  • targeted therapy
  • monitoring
  • prevention

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Published Papers (6 papers)

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Research

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18 pages, 4536 KiB  
Article
Molecular Epidemiology of Hepatitis D Virus in the North-East Region of Romania
by Laura Iulia Grecu, Mariana Pavel-Tanasa, Lilia Matei, Camelia Sultana, Simona Maria Ruta, Razvan Ioan Grecu, Ramona Gabriela Ursu, Petru Cianga and Luminita Smaranda Iancu
Pathogens 2024, 13(9), 793; https://doi.org/10.3390/pathogens13090793 - 13 Sep 2024
Cited by 2 | Viewed by 1216
Abstract
The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect [...] Read more.
The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect on hepatocytes and a significant impairment of the host immune response. The HDV genotype largely influences the extent of the pathogenic mechanisms with consequences on disease progression towards cirrhosis, liver decompensation, or hepatocellular carcinoma. In this context, identifying the circulating HDV genotypes in European regions with high prevalence, such as Romania, is crucial for effectively managing the long-term liver health. Here, we report the first comprehensive HDV study in Romania that clinically characterizes 82 patients and performs HDV genotyping by combining the nested-PCR reaction with sequencing analysis in 49 samples with an HDV-RNA load higher than 5000 IU/mL. While all isolates in our study belong to the HDV-1 genotype, the phylogenetic analysis based on sequence data from GenBank reveals the presence of the following potential three groups: (i) Italy and France; (ii) Spain; and (iii) Turkey, Iran, Pakistan, and Germany. This broad clustering highlights the recent surge in migration to and from Western Europe and the Middle East. Equally important, no differences in viral markers, clinical and paraclinical parameters, or treatment options were observed between these identified clusters. Nevertheless, this study considerably advances the understanding of hepatitis D epidemiology and clinical aspects in Romania. Full article
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Review

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8 pages, 438 KiB  
Review
Impact of Human Papillomavirus (HPV) on Male and Female Fertility
by Sara Chenafi-Adham, Oulfa Boussetta-Charfi, Sylvie Pillet and Thomas Bourlet
Pathogens 2024, 13(12), 1076; https://doi.org/10.3390/pathogens13121076 - 7 Dec 2024
Viewed by 1158
Abstract
Human papillomaviruses (HPVs) are responsible for the majority of sexually transmitted infections (STIs), some of which are oncogenic and can cause oropharyngeal or genital cancers. The HPV prevalence at the genital level varies according to the population studied but is higher in the [...] Read more.
Human papillomaviruses (HPVs) are responsible for the majority of sexually transmitted infections (STIs), some of which are oncogenic and can cause oropharyngeal or genital cancers. The HPV prevalence at the genital level varies according to the population studied but is higher in the seminal fluid of men suffering from idiopathic infertility than in the general population. The involvement of HPV in male infertility is supported by several studies suggesting that this virus can affect sperm quality by altering sperm DNA integrity, motility, number, viability, and morphology, and by inducing the production of anti-sperm antibodies (ASAs). HPVs may also have an impact on female fertility, mainly by increasing the risk of miscarriage and premature delivery and by altering the implantation of endometrial trophoblastic cells. In addition, an association with vaginal bacterial dysbiosis, notably involving Gardnerella vaginalis, or co-infection with an STI agent, serves as an aggravating factor. The aim of this review is to present current data on the potential role of HPVs in male and female infertility, along with data on infertility prevention and treatment strategies and the impact of vaccination in this context. Full article
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14 pages, 302 KiB  
Review
HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights
by Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess and Jad Chahoud
Pathogens 2024, 13(9), 809; https://doi.org/10.3390/pathogens13090809 - 18 Sep 2024
Cited by 1 | Viewed by 1862
Abstract
Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on [...] Read more.
Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications. Full article
19 pages, 785 KiB  
Review
The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses
by Nika Lovšin, Bhavani Gangupam and Martina Bergant Marušič
Pathogens 2024, 13(3), 187; https://doi.org/10.3390/pathogens13030187 - 20 Feb 2024
Cited by 5 | Viewed by 2633
Abstract
APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to [...] Read more.
APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3. Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3s in carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies. Full article
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12 pages, 295 KiB  
Review
p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?
by Roberto Gallus, Davide Rizzo, Giorgia Rossi, Luca Mureddu, Jacopo Galli, Alberto Artuso and Francesco Bussu
Pathogens 2024, 13(2), 100; https://doi.org/10.3390/pathogens13020100 - 24 Jan 2024
Viewed by 2355
Abstract
Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an [...] Read more.
Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papers and recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC’s cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker but on its independent role as a predictor of survival. Full article
20 pages, 699 KiB  
Review
The Clinical Utility of Circulating HPV DNA Biomarker in Oropharyngeal, Cervical, Anal, and Skin HPV-Related Cancers: A Review
by Ioana Maria Andrioaie, Ionut Luchian, Costin Dămian, Giorgio Nichitean, Elena Porumb Andrese, Theodor Florin Pantilimonescu, Bogdan Trandabăț, Liviu Jany Prisacariu, Dana Gabriela Budală, Daniela Cristina Dimitriu, Luminita Smaranda Iancu and Ramona Gabriela Ursu
Pathogens 2023, 12(7), 908; https://doi.org/10.3390/pathogens12070908 - 5 Jul 2023
Cited by 4 | Viewed by 2699
Abstract
Human papillomavirus (HPV) is recognized as being related to a wide variety of known cancers: cervical, oropharyngeal, anal, vaginal, penile, and skin. For some of these cancers, rigorous algorithms for screening, therapeutical interventions, and follow-up procedures have been established. Vaccination using the nonvalent [...] Read more.
Human papillomavirus (HPV) is recognized as being related to a wide variety of known cancers: cervical, oropharyngeal, anal, vaginal, penile, and skin. For some of these cancers, rigorous algorithms for screening, therapeutical interventions, and follow-up procedures have been established. Vaccination using the nonvalent anti-HPV vaccine, which prevents infection regarding the most frequently involved high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) and low-risk HPV types (6 and 11), has also extensively prevented, controlled, and even eradicated HPV infections. Still, even with all of these multidisciplinary interventions, the burden of HPV cancers is still high worldwide. The circulating DNA of HPV-induced cancers is thought to be an adequate biomarker for optimizing the control of these virus-related cancers. We analyzed the literature published in the last 5 years regarding ctDNA and four of the above-mentioned cancers. The most frequently used assay for ctDNA detection was the droplet digital PCR assay, used for the management of therapy in the late stages of cancer. ctDNA could not be used for early detection in any of the studied cancers. The OPSCCs were the most frequent cancers analyzed via ctDNA assays. Larger, properly designed cohort studies might establish the clinical utility of this biomarker. Full article
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