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Viruses
Special Issues
Biomarkers for Oncogenic Viruses
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Biomarkers for Oncogenic Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 9012

Special Issue Editors

Prof. Dr. Paul F. Lambert

E-Mail Website
Guest Editor
Director of McArdle Laboratory for Cancer Research/Chair of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
Interests: papillomavirus; anogenital cancer; head and neck cancer; merkel cell polyomavirus; merkel cell carcinoma; immune-evasion; oncogene; tumor suppressor
Dr. Wei Wang

E-Mail Website
Guest Editor
McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
Interests: papillomavirus; stress keratin 17; viral persistence; viral clearance; immunotherapy; check point blockade; T cell recruitment; tumor microenvironment; head and neck cancer, cervical cancer.

Special Issue Information

Dear Colleagues,

Biomarkers have become key tools for detecting cancers caused by viruses and lesions. Besides the detection of viruses and their products, host proteins that are altered in their expression are beneficial for discriminating virally caused cancers from other cancers. Emerging technologies are expanding our abilities to detect precancerous lesions and cancers associated with human tumor viruses and to monitor their recurrence and tumor microenvironment,  including liquid biopsies, single cell and/or spatial transcriptomics/proteomics, highly sensitive in situ hybridization techniques, and high-dimensional multiplex flow cytometry, among others. These emerging tools are useful at detecting not only biomarkers for virus-associated cancers at an early stage and at diagnosis, but also biomarkers for recurrence and patient response to therapies. We welcome primary papers and reviews that help move the field of biomarkers of oncogenic viruses forward.

Prof. Dr. Paul F. Lambert
Dr. Wei Wang
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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

  • tumor viruses
  • cancers
  • prevention
  • early detection
  • diagnostics
  • prognostics
  • immunotherapy
  • microenvironment
  • therapeutic targets
  • biomarkers

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Published Papers (5 papers)

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Research

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16 pages, 3125 KiB  
Article
A Distinct Anti-EBV DNase Profile in Patients with Undifferentiated Nasopharyngeal Carcinoma Compared to Classical Antigens
by Hamid Melouli, Abdelhalim Khenchouche, Fouzia Taibi-Zidouni, Dahmani Salma, Nassim Aoudia, Djamel Djennaoui, Tewfik Sahraoui, Samir Benyahia and Fatima Zohra El Kebir
Viruses 2023, 15(11), 2158; https://doi.org/10.3390/v15112158 - 26 Oct 2023
Viewed by 1438
Abstract
Nasopharyngeal cancer (NPC) is a prevalent type of cancer that often takes the form of undifferentiated carcinoma in the Maghreb region. It affects people of all ages. NPC diagnosis, mainly based on detecting Epstein-Barr virus (EBV), has not been well evaluated in North [...] Read more.
Nasopharyngeal cancer (NPC) is a prevalent type of cancer that often takes the form of undifferentiated carcinoma in the Maghreb region. It affects people of all ages. NPC diagnosis, mainly based on detecting Epstein-Barr virus (EBV), has not been well evaluated in North Africa. We compared the classical EBV serological tests using indirect immunofluorescence to the detection of EBV DNase antibodies by immunoblot in Algerian NPC patients. Significant variations were observed among different age groups of patients regarding the presence of VCA-IgA antibodies (0–14 and ≥30 years old, p < 0.0001; 15–19 and ≥30 years old, p < 0.01) and EA-IgA (0–14 and ≥30 years old, p < 0.01; 15–29 and ≥30 years old, p < 0.05). Differences were also noted in the titers of IgA anti-VCA and anti-EA antibodies across the three age groups. Some patients under the age of 30 with detectable IgG anti-VCA antibodies had undetectable IgA anti-VCA antibodies. These patients had a strong anti-DNase IgA response. However, older individuals had a higher level of anti-DNase IgG. Before treatment, children had strong DNase reactivity as indicated by specific IgA antibodies. Young adults had high IgA anti-DNase response, but the elderly (90.9%) had a lower response for these antibodies. Following therapy, the children retained high levels of IgA anti-DNase antibodies, and 66% of the young adults demonstrated robust antibody reactivity against DNase. In contrast, IgG responses to anti-DNase were low in children. This study demonstrated the utility of anti-DNase responses in the diagnosis and prognosis of NPC. Full article
(This article belongs to the Special Issue Biomarkers for Oncogenic Viruses)
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17 pages, 2712 KiB  
Article
Betapapillomaviruses in p16-Negative Vulvar Intraepithelial Lesions Associated with Squamous Cell Carcinoma
by Taja Lozar, Aysenur Keske, Racheal S. Dube Mandishora, Qiqi Yu, Adam Bailey, Jin Xu, Massimo Tommasino, Stephanie M. McGregor, Paul F. Lambert, Tarik Gheit and Megan B. Fitzpatrick
Viruses 2023, 15(9), 1950; https://doi.org/10.3390/v15091950 - 19 Sep 2023
Viewed by 1455
Abstract
Approximately 40% of vulvar squamous cell carcinoma (vSCC) cases are etiologically associated with high-risk human papillomaviruses (HPVs) of the alpha genera (α-HPV) that cause other anogenital cancers; however, the etiology of α-HPV-negative vSCC is poorly understood. HPVs of the beta genera (β-HPV) are [...] Read more.
Approximately 40% of vulvar squamous cell carcinoma (vSCC) cases are etiologically associated with high-risk human papillomaviruses (HPVs) of the alpha genera (α-HPV) that cause other anogenital cancers; however, the etiology of α-HPV-negative vSCC is poorly understood. HPVs of the beta genera (β-HPV) are risk factors for cutaneous squamous cell carcinoma (cSCC) and may be related to carcinomas originating in other cutaneous sites such as the vulva. In this study, we investigate the presence of β-HPVs, with an emphasis on p16-negative squamous lesions adjacent to vSCC. We subjected 28 vulvar squamous intraepithelial lesions adjacent to vSCC for comprehensive HPV genotyping, p16 and p53 immunohistochemistry, and consensus morphology review. Selected cases were subjected to qPCR and RNA in situ hybridization. Clinical data were obtained from medical records. β-HPV DNA was detected in eight of ten p16-negative lesions and three of fourteen p16-positive high-grade squamous intraepithelial lesions. The HPV DNA loads in vulvar squamous intraepithelial lesions ranged between less than 1 HPV DNA copy per cell to more than 100 HPV DNA copies per cell. This is, to the best of our knowledge, the first report of the association of p16-negative vulvar intraepithelial squamous lesions with detection of β-HPVs. These findings expand possible etiologic mechanisms that may contribute to p16-negative lesions of the vulva. Full article
(This article belongs to the Special Issue Biomarkers for Oncogenic Viruses)
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Review

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16 pages, 317 KiB  
Review
De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy
by Wendell G. Yarbrough, Travis P. Schrank, Barbara A. Burtness and Natalia Issaeva
Viruses 2024, 16(4), 536; https://doi.org/10.3390/v16040536 - 29 Mar 2024
Cited by 1 | Viewed by 1609
Abstract
Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and [...] Read more.
Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application. Full article
(This article belongs to the Special Issue Biomarkers for Oncogenic Viruses)
16 pages, 2796 KiB  
Review
Human Papillomavirus-Induced Chromosomal Instability and Aneuploidy in Squamous Cell Cancers
by Samyukta Mallick, Yeseo Choi, Alison M. Taylor and Pippa F. Cosper
Viruses 2024, 16(4), 501; https://doi.org/10.3390/v16040501 - 25 Mar 2024
Cited by 1 | Viewed by 1895
Abstract
Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. CIN is defined as a continuous rate of chromosome missegregation events over the course of multiple cell divisions. CIN causes aneuploidy, a state of abnormal chromosome content differing from a multiple of the haploid. [...] Read more.
Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. CIN is defined as a continuous rate of chromosome missegregation events over the course of multiple cell divisions. CIN causes aneuploidy, a state of abnormal chromosome content differing from a multiple of the haploid. Human papillomavirus (HPV) is a well-known cause of squamous cancers of the oropharynx, cervix, and anus. The HPV E6 and E7 oncogenes have well-known roles in carcinogenesis, but additional genomic events, such as CIN and aneuploidy, are often required for tumor formation. HPV+ squamous cancers have an increased frequency of specific types of CIN, including polar chromosomes. CIN leads to chromosome gains and losses (aneuploidies) specific to HPV+ cancers, which are distinct from HPV− cancers. HPV-specific CIN and aneuploidy may have implications for prognosis and therapeutic response and may provide insight into novel therapeutic vulnerabilities. Here, we review HPV-specific types of CIN and patterns of aneuploidy in squamous cancers, as well as how this impacts patient prognosis and treatment. Full article
(This article belongs to the Special Issue Biomarkers for Oncogenic Viruses)
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22 pages, 2220 KiB  
Review
Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
by Taja Lozar, Wei Wang, Niki Gavrielatou, Leslie Christensen, Paul F. Lambert, Paul M. Harari, David L. Rimm, Barbara Burtness, Cvetka Grasic Kuhar and Evie H. Carchman
Viruses 2023, 15(12), 2320; https://doi.org/10.3390/v15122320 - 25 Nov 2023
Cited by 2 | Viewed by 2077
Abstract
A growing body of literature suggests that the expression of cytokeratin 17 (K17) correlates with inferior clinical outcomes across various cancer types. In this scoping review, we aimed to review and map the available clinical evidence of the prognostic and predictive value of [...] Read more.
A growing body of literature suggests that the expression of cytokeratin 17 (K17) correlates with inferior clinical outcomes across various cancer types. In this scoping review, we aimed to review and map the available clinical evidence of the prognostic and predictive value of K17 in human cancers. PubMed, Web of Science, Embase (via Scopus), Cochrane Central Register of Controlled Trials, and Google Scholar were searched for studies of K17 expression in human cancers. Eligible studies were peer-reviewed, published in English, presented original data, and directly evaluated the association between K17 and clinical outcomes in human cancers. Of the 1705 studies identified in our search, 58 studies met criteria for inclusion. Studies assessed the prognostic significance (n = 54), predictive significance (n = 2), or both the prognostic and predictive significance (n = 2). Altogether, 11 studies (19.0%) investigated the clinical relevance of K17 in cancers with a known etiologic association to HPV; of those, 8 (13.8%) were focused on head and neck squamous cell carcinoma (HNSCC), and 3 (5.1%) were focused on cervical squamous cell carcinoma (SCC). To date, HNSCC, as well as triple-negative breast cancer (TNBC) and pancreatic cancer, were the most frequently studied cancer types. K17 had prognostic significance in 16/17 investigated cancer types and 43/56 studies. Our analysis suggests that K17 is a negative prognostic factor in the majority of studied cancer types, including HPV-associated types such as HNSCC and cervical cancer (13/17), and a positive prognostic factor in 2/17 studied cancer types (urothelial carcinoma of the upper urinary tract and breast cancer). In three out of four predictive studies, K17 was a negative predictive factor for chemotherapy and immune checkpoint blockade therapy response. Full article
(This article belongs to the Special Issue Biomarkers for Oncogenic Viruses)
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