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Pathogens
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Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy
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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: 30 September 2025 | Viewed by 17776

Special Issue Editor

Dr. Ramona Gabriela Ursu

E-Mail Website
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

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. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). 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

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

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Published Papers (10 papers)

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Research

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13 pages, 905 KiB  
Article
Impact of the Hepatitis B Immunization Strategy Adopted in Italy from 1991: The Results of a Seroprevalence Study on the Adult Population of Florence, Italy
by Sara Boccalini, Beatrice Zanella, Marco Del Riccio, Benedetta Bonito, Massimiliano Alberto Biamonte, Mario Bruschi, Giulia Ionita, Diana Paolini, Maddalena Innocenti, Lorenzo Baggiani, Monica Della Fonte, Giovanna Mereu, Paolo Bonanni, Working Group and Angela Bechini
Pathogens 2025, 14(4), 362; https://doi.org/10.3390/pathogens14040362 - 7 Apr 2025
Viewed by 274
Abstract
Italy was one of the first countries to implement a hepatitis B (HBV) immunization strategy in 1991; since its introduction, the epidemiology of this disease has significantly changed. The aim of this retrospective study was to assess the seroprevalence of three HBV markers [...] Read more.
Italy was one of the first countries to implement a hepatitis B (HBV) immunization strategy in 1991; since its introduction, the epidemiology of this disease has significantly changed. The aim of this retrospective study was to assess the seroprevalence of three HBV markers (anti-HBs, anti-HBc, and HBsAg) and describe the acquired immunity in a representative sample of the adult general population in the province of Florence (Italy) between April 2018 and December 2019. We conducted an enzyme-linked immunosorbent assay on 430 serum samples collected from the adult general population to quantify anti-HBs titers and assess the presence of anti-HBc and HBsAg. For the interpretation of hepatitis B serologic results, we referred to the US CDC guidelines. We conducted two multivariate logistic regression analyses (applied to the entire enrolled population and to the unvaccinated) to assess predictors of immunity against HBV using sex, age, and nationality as predictors. The overall anti-HBs prevalence was 30%, with a significant decreasing trend in seropositivity with increasing age. The overall anti-HBc prevalence was 11.6%, with seropositivity increasing with age. Only one subject tested positive for HBsAg (0.2%). Approximately 67.4% (290/430) of the study population was susceptible, 20.9% (90/430) was vaccinated, 9.1% (39/430) had naturally acquired immunity, and 0.2% (1/430) had an acute infection. Older age and foreign nationality were identified as risk factors in both multivariate logistic regression models. The comparison highlights a reduction in the circulation of HBV infection markers (anti-HBc and HBsAg) over 30 years in Tuscany, particularly in younger age groups. Our seroprevalence study demonstrated a good level of protection against hepatitis B, primarily among individuals under 40 years old, the target group of the vaccination strategy. Full article
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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18 pages, 3413 KiB  
Article
Improving HPV Vaccine Coverage in Tennessee: Addressing Barriers and Expanding Access for Mid-Adults
by Donald J. Alcendor, Patricia Matthews-Juarez, Mohammad Tabatabai, Derek Wilus, James E. K. Hildreth and Paul D. Juarez
Pathogens 2025, 14(4), 311; https://doi.org/10.3390/pathogens14040311 - 25 Mar 2025
Viewed by 334
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and the world. Infection with high-risk oncogenic HPV strains has been shown to induce cellular transformation leading to anogenital and oropharyngeal cancers. The HPV vaccine, first developed in 2006 for [...] Read more.
Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and the world. Infection with high-risk oncogenic HPV strains has been shown to induce cellular transformation leading to anogenital and oropharyngeal cancers. The HPV vaccine, first developed in 2006 for females aged 9–26 years, has been demonstrated to be safe and effective in preventing 90% of all HPV-associated cancers. However, vaccine hesitancy, misinformation, and barriers to vaccine access has resulted in suboptimal vaccination rates among adolescent populations, especially in rural communities in the South. HPV vaccine coverage in Tennessee is currently below the national average and below the Healthy People 2030 goal of an 80% vaccination rate for individuals 13–17 years old based on recommendation guidelines for up-to-date HPV vaccination status as of 2022. HPV vaccination rates for Tennesseans with private insurance in 2022 were 68% and 38% for those that were uninsured. Up-to-date HPV vaccination rates in 2022 for Tennesseans were 58% and 46% for those living in urban communities and rural communities, respectively. Overall, HPV-associated cancers rates are higher in Tennessee, at 12.9/100,000 compared to the overall rate in the US of 11.8/100,000 persons in 2022. Interventions to improve HPV vaccine awareness, education, and access could improve vaccine confidence and uptake, especially among rural and uninsured populations in Tennessee. Most recently, the Advisory Committee on Immunization Practices (ACIP) expanded recommendations for HPV vaccinations for some individuals aged 27–45 years who were not vaccinated at a younger age, with shared clinical decision making. Further research is needed to evaluate the impact of this recommendation on HPV vaccination rates and cancer prevention in Tennessee. Full article
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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17 pages, 3683 KiB  
Communication
A Combination of Flavonoids Suppresses Cell Proliferation and the E6 Oncogenic Pathway in Human Papillomavirus-Transformed Cells
by Federico De Marco, Fabio Altieri, Stefano Giuliani, Italia Falcone, Susanna Falcucci, Mariassunta Tedesco and Roberto Becelli
Pathogens 2025, 14(3), 221; https://doi.org/10.3390/pathogens14030221 - 24 Feb 2025
Cited by 1 | Viewed by 461
Abstract
Despite the availability of excellent HPV-specific vaccines, HPV-related conditions and, notably, their related neoplastic diseases are expected to impact human health for many years to come. Polyphenols and flavonoids are a large class of natural products, credited with a wide range of pharmacological [...] Read more.
Despite the availability of excellent HPV-specific vaccines, HPV-related conditions and, notably, their related neoplastic diseases are expected to impact human health for many years to come. Polyphenols and flavonoids are a large class of natural products, credited with a wide range of pharmacological properties including antineoplastic activity. However, the currently available data depict a rather heterogeneous and sometimes contradictory landscape, and no univocal conclusions can be drawn. To shed light on such a controversial issue, a restricted list of promising polyphenols were evaluated for their antineoplastic activity on HPV-transformed cells. Among them, Kaempferol, Galangin, and Luteolin proved to have distinct anti-clonal activity with ID50 values, respectively, of 1.25, 6.25, and 3.0 microMolar, and three other compounds, namely, Chrysin, Quercetin, and Apigenin, showed fair although less intense activity with ID values, respectively, of 25.0, 40, and 25 microMolar. Interestingly, a distinct anti-proliferative effect could also be suggested for Kaempferol, Luteolin, and Apigenine. Cooperative anti-clonal effects could be suggested for binary and ternary compositions made of Kaepferol, Galangin, and Luteolin once combined at concentrations ranging from 2 to 8 microMolar. At these concentrations, the single components and the triple combination induced distinct cell cycle modulation associated with marked restoration of the p53 and p21Cip1/Waf1 levels, consistent with the disruption of the E6/E6AP interaction whose continuous activity is necessary for both the induction and maintenance of the viral-induced neoplastic phenotype. Full article
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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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 1444
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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Review

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25 pages, 914 KiB  
Review
Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review
by Myrto Papamentzelopoulou and Vassiliki C. Pitiriga
Pathogens 2025, 14(3), 293; https://doi.org/10.3390/pathogens14030293 - 18 Mar 2025
Viewed by 661
Abstract
The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the [...] Read more.
The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases. Full article
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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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
Cited by 2 | Viewed by 1864
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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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 3 | Viewed by 2786
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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 2941
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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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
Cited by 2 | Viewed by 2632
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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 6 | Viewed by 2922
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
(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)
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