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Cancers
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Viruses in Cancer Etiology
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Viruses in Cancer Etiology

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

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 9889

Special Issue Editors

Dr. Natalia Issaeva

E-Mail Website
Guest Editor
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Interests: head and neck cancer; HPV-associated malignancies; p53
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Wendell G. Yarbrough

E-Mail Website
Guest Editor
1. Department of Otolaryngology/Head and Neck Surgery, The University of North Carolina, Chapel Hill, NC 27599-7070, USA
2. Department of Pathology and Lab Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA
3. Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA
Interests: head and neck cancer; HPV; HPV carcinogenesis

Special Issue Information

Dear Colleagues,

In total, around 10 to 20% of human cancers are caused by oncogenic viruses. At least seven viruses–Epstein–Barr virus, human papillomavirus, human T-cell lymphotropic virus, hepatitis B and C viruses, Kaposi's sarcoma herpesvirus, and Merkel cell polyomavirus–have well-established  roles in cancer progression and are relatively well-studied. These seven viruses belong to diverse taxonomic groups and infect different types of cells, resulting in the development of specific malignant tumors; however, they share several common features that contribute to their transformation, including their ability to regulate host cell proliferation and apoptosis, as well as immune response, in order to establish a chronic infection, and their propensity to inhibit tumor suppressors p53 and Rb.

Furthermore, a number of other viruses, usually not viewed as oncogenic, have been connected to human malignancies. Thus, almost half of human cancers have somatic retrotranspositions of long interspersed nuclear elements (Line1)—a repetitive element resembling retroviruses—and Line1-driven retrotransposition is a documented  source of complex structural genomic aberrations  and mutations in esophageal, head and neck, lung, and other tumors. Additionally, although not satisfactory and controversial, data exist indicating some involvement of simian vacuolating virus 40 (SV40) and human cytomegalovirus in cancer etiology.

The unique infectious nature of oncogenic viruses differentiatess them from other common causes of cancer and creates opportunities for exclusive anti-cancer treatments and cancer prevention, including some types of immunotherapies and prophylactic vaccination.

In this Special Issue, we welcome basic, translational, and clinical research papers, as well as comprehensive reviews, in the field of virus-associated cancer.

Dr. Natalia Issaeva
Prof. Dr. Wendell G. Yarbrough
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

  • oncogenic viruses
  • virus-related cancers
  • cancer progression
  • immune response
  • cancer etiology
  • anti-cancer treatment
  • immunotherapies
  • prophylactic vaccination

Published Papers (6 papers)

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Research

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11 pages, 2296 KiB  
Article
Epstein–Barr Virus and Clinico-Endoscopic Characteristics of Gastric Remnant Cancers Compared to Proximal Non-Remnant Cancers: A Population-Based Study
by Erling A. Bringeland, Christina Våge, Ann A. S. Ubøe, Alina D. Sandø, Patricia Mjønes and Reidar Fossmark
Cancers 2024, 16(11), 2000; https://doi.org/10.3390/cancers16112000 - 24 May 2024
Viewed by 185
Abstract
Epstein–Barr virus (EBV) is associated with 5–10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are [...] Read more.
Epstein–Barr virus (EBV) is associated with 5–10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001–2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7–68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
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10 pages, 256 KiB  
Article
Association of Nasopharynx Cancer with Human Papillomavirus Infections
by Shih-Han Hung, Tzong-Hann Yang, Yen-Fu Cheng, Chin-Shyan Chen and Herng-Ching Lin
Cancers 2023, 15(16), 4082; https://doi.org/10.3390/cancers15164082 - 13 Aug 2023
Cited by 3 | Viewed by 1199
Abstract
This population-based study aims to examine the association between nasopharyngeal carcinoma and human papillomavirus infections. This study included 2747 individuals aged 20 years and older who were diagnosed with nasopharynx cancer as cases and 13,735 propensity-score-matching controls. Multivariate logistic regression models were employed [...] Read more.
This population-based study aims to examine the association between nasopharyngeal carcinoma and human papillomavirus infections. This study included 2747 individuals aged 20 years and older who were diagnosed with nasopharynx cancer as cases and 13,735 propensity-score-matching controls. Multivariate logistic regression models were employed to quantitatively assess the association of nasopharynx cancer with human papillomavirus infections while considering age, sex, monthly income, geographic location, and urbanization level of the patient’s residence as well as diabetes, hypertension, and hyperlipidemia. Our chi-squared test indicated a significant dissimilarity in previous human papillomavirus infection rates between nasopharynx cancer patients and controls (12.7% vs. 7.2%, p < 0.001). The adjusted odds ratio (OR) for prior human papillomavirus infections was found to be significantly higher for nasopharyngeal carcinoma cases compared to controls at a value of 1.869 with confidence interval ranging from 1.640 to 2.128. Among female participants, compared to controls, the adjusted OR of prior human papillomavirus infections was 2.150 (95% CI = 1.763–2.626) in patients with nasopharynx cancer. In male participants sampled in this study, we observed a statistically significant association between prior human papillomavirus infections and nasopharynx cancer (adjusted OR = 1.689; 95% CI = 1.421–2.008). Our study indicates a noteworthy association between previous human papillomavirus infections and nasopharyngeal carcinoma. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
12 pages, 976 KiB  
Article
In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix and HPV-Type Impact: Pathologic Features, Treatment Options, and Follow-Up Outcomes—Cervical Adenocarcinoma Study Group (CAS-Group)
by Luca Giannella, Giovanni Delli Carpini, Jacopo Di Giuseppe, Giorgio Bogani, Francesco Sopracordevole, Nicolò Clemente, Giorgio Giorda, Rosa Pasqualina De Vincenzo, Maria Teresa Evangelista, Barbara Gardella, Mattia Dominoni, Ermelinda Monti, Chiara Alessi, Lara Alessandrini, Alessio Pagan, Marta Caretto, Alessandro Ghelardi, Andrea Amadori, Massimo Origoni, Maggiorino Barbero, Francesco Raspagliesi, Tommaso Simoncini, Paolo Vercellini, Giovanni Scambia and Andrea Ciavattiniadd Show full author list remove Hide full author list
Cancers 2023, 15(11), 2876; https://doi.org/10.3390/cancers15112876 - 23 May 2023
Cited by 5 | Viewed by 2165
Abstract
It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed [...] Read more.
It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed in women with available HPV testing before treatment. One hundred and forty-eight consecutive women were analyzed. The number of HPV-negative cases was 24 (16.2%). The survival rate was 100% in all participants. The recurrence rate was 7.4% (11 cases, including four invasive lesions (2.7%)). Cox proportional hazards regression showed no difference in recurrence rate between HPV-positive and HPV-negative cases (p = 0.148). HPV genotyping, available for 76 women and including 9/11 recurrences, showed a higher relapse rate for HPV-18 than HPV-45 and HPV-16 (28.5%, 16.6%, and 9.52%, p = 0.046). In addition, 60% and 75% of in situ and invasive recurrences, respectively, were HPV-18 related. The present study showed that most ACs were positive for high-risk HPV, and the recurrence rate was unaffected by HPV status. More extensive studies could help evaluate whether HPV genotyping may be considered for recurrence risk stratification in HPV-positive cases. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
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17 pages, 4178 KiB  
Article
Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells
by Blue-leaf A. Cordes, Andrea Bilger, Richard J. Kraus, Ella T. Ward-Shaw, Madeline R. Labott, Shinhyo Lee, Paul F. Lambert and Janet E. Mertz
Cancers 2023, 15(6), 1846; https://doi.org/10.3390/cancers15061846 - 19 Mar 2023
Viewed by 1784
Abstract
Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV’s latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we [...] Read more.
Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV’s latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we tested three classes of these drugs for preferential killing of the EBV-positive gastric cancer AGS-Akata cell line compared to its matched EBV-negative AGS control. We observed preferential killing with iron chelators [Deferoxamine (DFO); Deferasirox (DFX)] and a prolyl hydroxylase inhibitor (BAY 85-3934 (Molidustat)), but not with a neddylation inhibitor [MLN4924 (Pevonedistat)]. DFO and DFX also induced preferential killing of the EBV-positive gastric cancer AGS-BDneo and SNU-719 cell lines. Preferential killing was enhanced when low-dose DFX (10 μM) was combined with the antiviral prodrug ganciclovir. DFO and DFX induced lytic EBV reactivation in approximately 10% of SNU-719 and 20-30% of AGS-Akata and AGS-BDneo cells. However, neither DFO nor DFX significantly induced synthesis of lytic EBV proteins in xenografts grown in NSG mice from AGS-Akata cells above the level observed in control-treated mice. Therefore, these FDA-approved iron chelators are less effective than gemcitabine at promoting EBV reactivation in vivo despite their high specificity and efficiency in vitro. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
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Review

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13 pages, 481 KiB  
Review
A Historical Overview on the Role of Hepatitis B and C Viruses as Aetiological Factors for Hepatocellular Carcinoma
by Tommaso Stroffolini and Giacomo Stroffolini
Cancers 2023, 15(8), 2388; https://doi.org/10.3390/cancers15082388 - 20 Apr 2023
Cited by 9 | Viewed by 2349
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the [...] Read more.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
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Other

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10 pages, 1087 KiB  
Perspective
Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations
by Roberto Gallus, Irene H Nauta, Linda Marklund, Davide Rizzo, Claudia Crescio, Luca Mureddu, Paolo Tropiano, Giovanni Delogu and Francesco Bussu
Cancers 2023, 15(3), 656; https://doi.org/10.3390/cancers15030656 - 20 Jan 2023
Cited by 3 | Viewed by 1643
Abstract
High-risk human papillomavirus (HPV) infection is a defined etiopathogenetic factor in oropharyngeal carcinogenesis with a clear prognostic value. The P16 IHC (immunohistochemistry) is a widely accepted marker for HPV-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC); in the present paper, we discuss its [...] Read more.
High-risk human papillomavirus (HPV) infection is a defined etiopathogenetic factor in oropharyngeal carcinogenesis with a clear prognostic value. The P16 IHC (immunohistochemistry) is a widely accepted marker for HPV-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC); in the present paper, we discuss its reliability as a standalone marker in different populations. The literature suggests that rates of p16 IHC false positive results are inversely correlated with the prevalence of HPV-driven carcinogenesis in a population. We propose a formula that can calculate such a false positive rate while knowing the real prevalence of HPV-driven OPSCCs in a given population. As it has been demonstrated that p16 positive/HPV negative cases (i.e., false positives at p16 IHC) have the same prognosis as p16 negative OPSCC, we conclude that despite the valuable prognostic value of p16 IHC, relying only on a p16 IHC positive result to recommend treatment de-intensification could be risky. For this aim, confirmation with an HPV nucleic acid detection system, especially in areas with a low prevalence of HPV-related OPSCCs, should be pursued. Full article
(This article belongs to the Special Issue Viruses in Cancer Etiology)
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