Chronic Viral Infections and Cancer, Openings for Therapies and Vaccines

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 19813

Special Issue Editors

1. Department of Research, Riga Stradins University, LV-1007 Riga, Latvia
2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Interests: chronic viral infections and associated cancer; human immunodeficiency virus type 1; human hepatitis C virus; oxidative stress; T cell response; B cell response; DNA vaccines
Special Issues, Collections and Topics in MDPI journals
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
Interests: hepatitis virus; SARS-CoV-2; influenza virus; metabolomics; polyamines; antiviral agents
Special Issues, Collections and Topics in MDPI journals
Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Naples, Italy
Interests: oncology; molecular biology; virology; biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Approximately one out of eight human cancers has a viral etiology. Viral cancers open unique opportunities for prophylaxis, diagnosis, and therapy, as demonstrated by the success of HBV and HPV vaccines, as well as HCV antivirals in decreasing the incidence of tumors associated with these infections.

For other chronic viral infections and associated cancers, problems still dominate over progress. Prophylactic HPV vaccination does not cure already established infections, although an adjuvant role has been identified following conventional treatment, urgently requesting development of therapeutic HPV vaccines. Several are in the pipeline, but still far from actual application for treatment of HPV-related cancers. Development of HCV vaccines is in progress but hampered by HCV variability and absence of longitudinal sterilizing antiviral response. The success of antiretroviral therapy in controlling HIV-1 replication and immune reconstitution did not lead to significant reduction in HIV-1 associated cancers, indicating alternative mechanisms of their development not connected to immune suppression, requiring in-depth study and clinical interventions.

In this Special Issue, we aim to unravel the progress in the studies of the molecular pathogenesis of chronic viral infections and cover the common mechanisms of action of human oncogenic viruses, such as the activity of viral oncoproteins, the induction of genomic instability, the support of chronic inflammation, and the modulation of tumor microenvironment. Special attention will be devoted to virus-induced alterations in the functions of the immune system, to induction of innate and adaptive immune responses, including the relationship between immune response and viral infections, metabolism, and immunometabolism, as well as to oncolytic viruses. In-depth understanding of these processes would create new openings for the design of novel viral vaccines and immunotherapies.

A special invitation to submit is addressed to the participants of the international symposium “Chronic Viral Infections and Cancer, Openings for Vaccines” held online on 16–17 December 2021 www.techvac.org, sponsored by Cancers

Dr. Maria G. Isaguliants
Dr. Alexander Ivanov
Dr. Franco M. Buonaguro
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • chronic viral infection
  • high-risk human papillomaviruses
  • Epstein–Barr virus
  • human hepatitis C virus
  • human hepatitis B virus
  • human hepatitis D virus
  • human immunodeficiency virus type I
  • cancer
  • metastasis
  • oxidative stress
  • metabolism
  • immunometabolism
  • genomic instability
  • DNA damage
  • innate immunity
  • adaptive immunity
  • viral vaccines
  • cancer vaccines
  • adjuvants
  • immunotherapy
  • animal models of chronic viral infections and cancer

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

7 pages, 203 KiB  
Editorial
Chronic Viral Infections and Cancer, Openings for Therapies and Vaccines
Cancers 2024, 16(4), 818; https://doi.org/10.3390/cancers16040818 - 18 Feb 2024
Viewed by 478
Abstract
Infections are responsible for approximately one out of six cases of cancer worldwide [...] Full article

Research

Jump to: Editorial, Review, Other

12 pages, 914 KiB  
Article
Prevalence and Characteristics of Human Papillomavirus Infection in Oropharyngeal Squamous Cell Papilloma
Cancers 2023, 15(3), 810; https://doi.org/10.3390/cancers15030810 - 28 Jan 2023
Cited by 1 | Viewed by 1169
Abstract
Studies on human papillomavirus (HPV) infection in oropharyngeal squamous papilloma (OPSP) are lacking, although HPV infection has been recognized as the primary cause of oropharyngeal cancer for several decades. This study aimed to evaluate the prevalence and characteristics of HPV infections in patients [...] Read more.
Studies on human papillomavirus (HPV) infection in oropharyngeal squamous papilloma (OPSP) are lacking, although HPV infection has been recognized as the primary cause of oropharyngeal cancer for several decades. This study aimed to evaluate the prevalence and characteristics of HPV infections in patients with OPSP. We retrospectively enrolled patients with histologically confirmed OPSP in whom the presence of HPV infections and p16 expression were evaluated. The results of HPV infection in OPSP were analyzed according to the clinicodemographic profiles. Of the 83 patients included in this study, HPV test results were positive in 12 patients, with an overall prevalence of 14.5%. HPV genotypes involved low-risk and high-risk HPV types in three (3.6%) and nine (10.8%) patients, respectively. The most prevalent genotype was HPV16, accounting for 58.3% of all HPV infections. None of the OPSPs showed p16 IHC positivity. There were trends toward a higher prevalence of high-risk HPV infection in patients with OPSP aged ≤45 years, never-smokers, and those with multifocal diseases. These findings could enhance our understanding of HPV infection in OPSP and be used as valuable epidemiological data for the management of HPV-associated OPSP and regarding the possible efficacy of HPV vaccinations in OPSP. Full article
Show Figures

Figure 1

12 pages, 14229 KiB  
Article
Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study
Cancers 2023, 15(3), 643; https://doi.org/10.3390/cancers15030643 - 19 Jan 2023
Cited by 3 | Viewed by 3203
Abstract
Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of [...] Read more.
Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004–0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01–0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia. Full article
Show Figures

Figure 1

18 pages, 2754 KiB  
Article
SARS-CoV-2 Establishes a Productive Infection in Hepatoma and Glioblastoma Multiforme Cell Lines
Cancers 2023, 15(3), 632; https://doi.org/10.3390/cancers15030632 - 19 Jan 2023
Cited by 3 | Viewed by 2153
Abstract
Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, [...] Read more.
Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation. Here, we explored the possible infection of hepatic and CNS cell lines by SARS-CoV-2. We show that even moderate expression levels of the angiotensin-converting enzyme 2 (ACE2) are sufficient for productive infection. SARS-CoV-2 infects hepatoma Huh7.5 and HepG2 cells but not non-transformed liver progenitor or hepatocyte/cholangiocyte-like HepaRG cells. However, exposure to the virus causes partial dedifferentiation of HepaRG cells. SARS-CoV-2 can also establish efficient replication in some low-passage, high-grade glioblastoma cell lines. In contrast, embryonal primary astrocytes or neuroblastoma cells did not support replication of the virus. Glioblastoma cell permissiveness is associated with defects in interferon production. Overall, these results suggest that liver dysfunction during COVID-19 is not due to infection of these tissues by SARS-CoV-2. Furthermore, tumors may potentially serve as reservoirs for the virus during infection. Full article
Show Figures

Figure 1

13 pages, 2592 KiB  
Article
HPV16 E7 Nucleotide Variants Found in Cancer-Free Subjects Affect E7 Protein Expression and Transformation
Cancers 2022, 14(19), 4895; https://doi.org/10.3390/cancers14194895 - 06 Oct 2022
Cited by 7 | Viewed by 1538
Abstract
The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed [...] Read more.
The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed full-length HPV16 E7 genes and tested variants at positions H9R, D21N, N29S, E33K, T56I, D62N, S63F, S63P, T64M, E80K, D81N, P92L, and P92S (found only in controls); D14E, N29H cervical intraepithelial neoplasia (CIN2), and P6L, H51N, R77S (CIN3). We determined the steady-state level of cytoplasmic and nuclear HPV16 E7 protein. All variants from controls showed a reduced level of E7 protein, with 7/13 variants having lower protein levels. In contrast, 2/3 variants from the CIN3 precancer group had near-wild type E7 levels. We assayed the activity of representative variants in stably transfected NIH3T3 cells. The H9R, E33K, P92L, and P92S variants found in control subjects had lower transforming activity than D14E and N29H variants (CIN2), and the R77S (CIN3) had activity only slightly reduced from wild-type E7. In addition, R77S and WT E7 caused increased migration of NIH3T3 cells in a wound-healing assay compared with H9R, E33K, P92L, and P92S (controls) and D14E (CIN2). These data provide evidence that the E7 variants found in HPV16-positive cancer-free women are partially defective for transformation and cell migration, further demonstrating the importance of fully active E7 in cancer development. Full article
Show Figures

Figure 1

18 pages, 4101 KiB  
Article
Oncogenic and Stemness Signatures of the High-Risk HCMV Strains in Breast Cancer Progression
Cancers 2022, 14(17), 4271; https://doi.org/10.3390/cancers14174271 - 01 Sep 2022
Cited by 9 | Viewed by 2170
Abstract
Background: Human cytomegalovirus (HCMV) oncomodulation, molecular mechanisms, and ability to support polyploid giant cancer cells (PGCCs) generation might underscore its contribution to oncogenesis, especially breast cancers. The heterogeneity of strains can be linked to distinct properties influencing the virus-transforming potential, cancer types induced, [...] Read more.
Background: Human cytomegalovirus (HCMV) oncomodulation, molecular mechanisms, and ability to support polyploid giant cancer cells (PGCCs) generation might underscore its contribution to oncogenesis, especially breast cancers. The heterogeneity of strains can be linked to distinct properties influencing the virus-transforming potential, cancer types induced, and patient’s clinical outcomes. Methods: We evaluated the transforming potential in vitro and assessed the acquired cellular phenotype, genetic and molecular features, and stimulation of stemness of HCMV strains, B544 and B693, isolated from EZH2HighMycHigh triple-negative breast cancer (TNBC) biopsies. Therapeutic response assessment after paclitaxel (PTX) and ganciclovir (GCV) treatment was conducted in addition to the molecular characterization of the tumor microenvironment (TME). Findings: HCMV-B544 and B693 transformed human mammary epithelial cells (HMECs). We detected multinucleated and lipid droplet-filled PGCCs harboring HCMV. Colony formation was detected and Myc was overexpressed in CMV-Transformed-HMECs (CTH cells). CTH-B544 and B693 stimulated stemness and established an epithelial/mesenchymal hybrid state. HCMV-IE1 was detected in CTH long-term cultures indicating a sustained viral replication. Biopsy B693 unveiled a tumor signature predicting a poor prognosis. CTH-B544 cells were shown to be more sensitive to PTX/GCV therapy. Conclusion: The oncogenic and stemness signatures of HCMV strains accentuate the oncogenic potential of HCMV in breast cancer progression thereby leading the way for targeted therapies and innovative clinical interventions that will improve the overall survival of breast cancer patients. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

18 pages, 315 KiB  
Review
DNA and mRNA Vaccines for Chronic Viral Infections and Cancer: Rationale, Mechanisms, and Progress
Cancers 2022, 14(23), 5874; https://doi.org/10.3390/cancers14235874 - 29 Nov 2022
Cited by 1 | Viewed by 1348
Abstract
Interest in the capabilities of nucleic acid vaccines, (DNA and mRNA vaccines) for both prophylactic and therapeutic uses have greatly increased following the successful deployment of two mRNA and, on a more limited scale, one DNA vaccine for COVID-19. In addition to targeting [...] Read more.
Interest in the capabilities of nucleic acid vaccines, (DNA and mRNA vaccines) for both prophylactic and therapeutic uses have greatly increased following the successful deployment of two mRNA and, on a more limited scale, one DNA vaccine for COVID-19. In addition to targeting other pathogens for prophylactic vaccines, efforts are also being made towards using them for therapies for chronic infections and cancer. An examination of past and current successes for such therapies using other technologies with an emphasis on the immunological mechanisms will be provided followed by an assessment of the relevant characteristics of DNA and mRNA vaccines to predict their utility for therapies for chronic viral infections and cancer. Efforts and progress for these targets will be described. Full article
29 pages, 1903 KiB  
Review
An Update on the Metabolic Landscape of Oncogenic Viruses
Cancers 2022, 14(23), 5742; https://doi.org/10.3390/cancers14235742 - 23 Nov 2022
Cited by 2 | Viewed by 1565
Abstract
Viruses play an important role in cancer development as about 12% of cancer types are linked to viral infections. Viruses that induce cellular transformation are known as oncoviruses. Although the mechanisms of viral oncogenesis differ between viruses, all oncogenic viruses share the ability [...] Read more.
Viruses play an important role in cancer development as about 12% of cancer types are linked to viral infections. Viruses that induce cellular transformation are known as oncoviruses. Although the mechanisms of viral oncogenesis differ between viruses, all oncogenic viruses share the ability to establish persistent chronic infections with no obvious symptoms for years. During these prolonged infections, oncogenic viruses manipulate cell signaling pathways that control cell cycle progression, apoptosis, inflammation, and metabolism. Importantly, it seems that most oncoviruses depend on these changes for their persistence and amplification. Metabolic changes induced by oncoviruses share many common features with cancer metabolism. Indeed, viruses, like proliferating cancer cells, require increased biosynthetic precursors for virion production, need to balance cellular redox homeostasis, and need to ensure host cell survival in a given tissue microenvironment. Thus, like for cancer cells, viral replication and persistence of infected cells frequently depend on metabolic changes. Here, we draw parallels between metabolic changes observed in cancers or induced by oncoviruses, with a focus on pathways involved in the regulation of glucose, lipid, and amino acids. We describe whether and how oncoviruses depend on metabolic changes, with the perspective of targeting them for antiviral and onco-therapeutic approaches in the context of viral infections. Full article
Show Figures

Figure 1

20 pages, 939 KiB  
Review
The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development
Cancers 2022, 14(21), 5257; https://doi.org/10.3390/cancers14215257 - 26 Oct 2022
Cited by 3 | Viewed by 1755
Abstract
Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s [...] Read more.
Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus–telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses. Full article
Show Figures

Graphical abstract

10 pages, 512 KiB  
Review
Poly(ADP-Ribose) Polymerase Inhibition as a Promising Approach for Hepatocellular Carcinoma Therapy
Cancers 2022, 14(15), 3806; https://doi.org/10.3390/cancers14153806 - 05 Aug 2022
Viewed by 1581
Abstract
Primary liver cancer is the sixth most common cancer in men and seventh in women, with hepatocellular carcinoma (HCC) being the most common form (75–85% of primary liver cancer cases) and the most frequent etiology being viral infections (HBV and HCV). In 2020, [...] Read more.
Primary liver cancer is the sixth most common cancer in men and seventh in women, with hepatocellular carcinoma (HCC) being the most common form (75–85% of primary liver cancer cases) and the most frequent etiology being viral infections (HBV and HCV). In 2020, mortality represented 92% of the incidence—830,180 deaths for 905,677 new cases. Few treatment options exist for advanced or terminal-stage HCC, which will receive systemic therapy or palliative care. Although radiotherapy is used in the treatment of many cancers, it is currently not the treatment of choice for HCC, except in the palliative setting. However, as radiosensitizing drugs, such as inhibitors of DNA repair enzymes, could potentiate the effects of RT in HCC by exploiting the modulation of DNA repair processes found in this tumour type, RT and such drugs could provide a treatment option for HCC. In this review, we provide an overview of PARP1 involvement in DNA damage repair pathway and discuss its potential implication in HCC. In addition, the use of PARP inhibitors and PARP decoys is described for the treatment of HCC and, in particular, in HBV-related HCC. Full article
Show Figures

Figure 1

Other

21 pages, 1661 KiB  
Systematic Review
Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review
Cancers 2024, 16(3), 672; https://doi.org/10.3390/cancers16030672 - 05 Feb 2024
Viewed by 901
Abstract
Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity [...] Read more.
Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT. Full article
Show Figures

Figure 1

Back to TopTop