You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Merkel Cell Polyomavirus and β Human Papillomavirus Types: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Ramona Gabriela Ursu.

Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPyV and beta HPV types) to be implemented in each region’s/country’s cancer centres’ molecular detection diagnostic platforms, with multiplex viral capability, optimal sensitivity, and specificity; clinically validated, and if possible, at acceptable costs. For confirmatory diagnosis of skin cancer, another method should be used, with a different principle, such as immunohistochemistry, with specific antibodies for each virus.

  • skin cancer
  • Merkel cell polyomavirus
  • polyomaviruses

1. Introduction

The International Agency for Research on Cancer (IARC) recognized the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatis C virus (HCV), Kaposi’s sarcoma herpes virus (or human gammaherpesvirus 8), human immunodeficiency virus 1 (HIV-1), several human papillomavirus (HPV) types, and human-T lymphotropic retrovirus-1 (HTLV-1) as biological agents involved in human carcinogenesis. Criteria used to prove the involvement of these viruses in the tumorigenesis process was based on analyzing exposure data, studies on cancer in humans and in animal models, and identification of relevant data providing mechanistic insight. Exposure data refer to general information about the agent, analysis and detection methods regarding sensitivity and specificity, occurrence, and exposure. Research of cancer in humans analyzed the type of studies (cohort studies, case-control studies), meta-analyses and pooled analyses, temporal effect, the use of biomarkers in epidemiological studies, and criteria of causality. Model animal studies investigated the qualitative and quantitative aspects, and mechanistic insight referred to toxicokinetic data, mechanisms of carcinogenesis which identified functional changes at the cellular level and alterations at the molecular level [1].
The estimated age-standardized incidence rates in 2020 for skin melanoma and non-melanoma skin cancer, both genders, all ages, WHO Europe, mention Switzerland, Ireland, and The Netherlands in the first three places, with age-standardized rates (ASR) 71.1, 63.3, and 61.5, respectively, with Romania having an ASR of 12.0 [2]. This data collection regarding the incidence of cancer is powered by population-based cancer registries which are available in developed countries; this led to the idea that in countries without population-based cancer registries, the incidence of cancers is underreported. Skin cancer is known to have several risk factors, such as sun exposure, BRAF mutation in melanoma patients, and some molecular factors [3,4][3][4]. The higher incidence of NMSC (nonmelanoma skin cancer) in immunocompromised patients points to a possible viral origin [5].

2. Merkel Cell Polyomavirus

The Polyomaviridae family includes numerous small, icosahedral, non-enveloped viruses, which have a double-stranded DNA genome that is approximately 5000 base pairs in length, and it is packed together with histones uptake from the host cells. These viruses have a wide range of hosts, including mammals, birds, and fish [6]. The International Committee on Taxonomy of Viruses (ICTV) currently recognizes eight different genera of polyomaviruses (Alpha-, Beta-, Gamma, Delta-, Epsilon-, Zeta-, Eta- and Thetapolyomavirus), comprising a total of 117 species [7]. The genetic diversity of these viruses is also very great, and a characteristic co-speciation with their hosts has been observed, which is a result of genetic recombination, as it has been observed for papillomaviruses [8]. Many of the viruses in this family are associated with an oncogenic capacity in animal hosts, which has been observed since the discovery of murine polyomavirus in the 1950s. The Polyomaviridae family was given this name because of the numerous types of tumors they can induce (polyoma) [9].
Of the human polyomaviruses, MCPyV was the first one for which evidence of carcinogenic potential has been observed, in a rare and aggressive form of skin cancer named Merkel cell carcinoma (MCC). MCPyV was first discovered at the Pittsburgh Cancer Institute in 2008, using digital transcriptome subtraction assays. The reseauthorchers detected that the viral DNA integrated within the tumoral cells’ genome in a clonal pattern, in 6/8 MCPyV-positive MCCs, suggesting that MCPyV infection and integration preceded clonal expansion of the tumoral cells. MCPyV was then first considered to have a contributing factor in the pathogenesis of MCC [10]. Four years later, scientists from 11 countries met at IARC, to evaluate the carcinogenicity of MCPyV, and their research has been published in a monograph and in a Lancet paper. By analyzing all the research studies published since its discovery, the reseauthorchers concluded that there is powerful mechanistic evidence that MCPyV can directly contribute to the development of a large proportion of MCCs. Using PCR, many independent laboratories have detected MCPyV DNA in about three quarters of more than 1000 MCC cases [11,12][11][12].
In 2017–2018, a multidisciplinary team from important research centers of many continents (e.g., German Cancer Research Centre, DKFZ, Heidelberg, Germany, Department of Melanoma Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Centre, Houston, TX, USA, Peter McCallum Cancer Centre, Melbourne, Australia, to name just a few) published three revisewsarch regarding MCPyV in relation to skin cancer [13,14,15][13][14][15].
Becker JC et al., classified MCCs in MCPyV positive and negative and mentioned that in the countries with low UV exposure, MCPyV is present in most of the skin cancers, in stark contrast with countries with high UV exposure where the virus is absent in MCCs. It is interesting that both MCC types have similar phenotypes, and several tissue markers were detected in skin cancer that may be positive or not for MCPyV, including apoptosis regulator B-cell lymphoma-2 (BCL2), cytokeratin 20, neural cell adhesion molecule 1, CD99, CD99 antigen, epithelial cell adhesion molecule, huntingtin-interacting protein 1, neuron-specific enolase, and neurogenic locus notch homologue protein 1. The MCPyV-specific MCC viral markers are large T antigen and small T antigen. The reseauthorchers mentioned that, in the case of viral-positive MCC cases, the genetic aberrations observed are from perturbations of signaling pathways by antigens and genome integration; meanwhile, in the case of UV exposure, other alterations were detected, such as deletions, translocations, and point mutations [13].
In the second revisewarch [14], members of the EU IMMOMEC (European Union Immune Modulating strategies for treatment of Merkel Cell Carcinoma) presented the actual available therapy that is efficient for this type of skin cancer: the immune checkpoint-inhibiting antibodies pembrolizumab and avelumab [specifically, the programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) blocking antibodies]. This new therapy seems to be efficient in more than half of the treated MCC patients. Still, a targeted therapy is still necessary, as many MCC patients are immunosuppressed and their response to immune checkpoint inhibition is not possible [15].
In 2018, the International Workshop on Merkel Cell Carcinoma Research (IWMCC) working group underlined some open research questions regarding this primary cutaneous neuroendocrine carcinoma, MCC: the multidisciplinary research team (e.g., virology, pathology, oncology, dermatology) raised awareness regarding future targeted therapy in both MCPyV positive and MCPyV negative cases of MCC, and about the optimal detection assay for this virus [15].

3. Cutaneous HPV Types

The Papillomaviridae family is comprised of small, icosahedral, non-enveloped viruses with a double-stranded DNA genome, and are also characterized by a great genetic diversity and wide range of hosts, including mammals, birds, reptiles, and fish. They also have a known oncogenic potential in humans, most importantly in the development of cervical cancer, but also vulvar, vaginal, penile, and oropharyngeal cancers. The human papillomaviruses which are associated with those cancers are also called mucosal, high-risk, or alpha HPV types [16].
The first classification of cutaneous papillomaviruses was performed by de Villiers EM et al., in 2004 [17]. In 2012, the IARC monograph reported that, up to that moment, there was no HPV type which could be considered to cause skin cancer, due to the lack of consistency of the published data. In 2012, it was considered that the role of HPV types in skin cancers could be complex, possibly associated with other co-factors, such as UV exposure [1]. In 2013, over 170 human papillomavirus types were reported to be associated with different clinical manifestations in humans, with the skin being the main site, followed by mucosa (vagina, mouth) and gut [18].
In a similar manner to MCPyV, for cutaneous HPV types, important revisewsarch were recently published, with a different view regarding the involvement of these viruses in skin cancer.
Venuti A et al., analyzed the “cross-talk” between cutaneous HPV types and the immune system, in a journal of the Royal Society; they mentioned the “hit-and-run” hypothesis, having the ability to initiate the first steps of UV-driven skin carcinogenesis, a different mechanism of carcinogenesis, in comparison with that of mucosal HPV types responsible for cervical cancer. The reseauthorchers underlined the necessity of understanding the cross-talk with host cell-autonomous and extrinsic immunity for it to be possible to identify novel therapies against beta HPV, besides their sensitivity to interferon regulatory factors [19].
Gheit T., 2019, an IARC researcher with impressive experience in HPV testing and analyzing, presented the main features and functions of the early and late gene products from alpha and beta HPV types. Interestingly, for E6 and E7 genes known as oncogenic in cervical cancer, different functions are underlined: both genes are not required for the maintenance of the cancer phenotype. E6 interacts with the Notch pathway and promotes the transformation process of the infected keratinocytes, and inhibits the differentiation of HPV8-expressing keratinocytes by targeting the PDZ domain-containing protein syntenin 2. E7 from HPV38 shows the ability to counteract p53-mediated apoptosis by inducing an accumulation of the p73 isoform, 1Np73 [16]. The reseauthorrchers was in support of the hypothetical carcinogenesis mechanism of the previous review [19]research[19], mentioning that E6 and E7 expression appear to be required only at the initial step of skin carcinogenesis by exacerbating the deleterious effects of UV radiation [16].
Rollison DE et al., 2019, mentioned that since the first meeting group at IARC regarding beta HPV types, 50 types of cutaneous HPV have been identified from a total of 200 HPV types. The reseauthorchers underlined the importance of UV as a co-factor in skin carcinogenesis, in the case of constant stress, and it is considered that cutaneous HPV types facilitate DNA damage accumulation induced by UV radiation. This review used high-risk HPV (HR-HPV) types as a comparison, and the authoresearchers are confident that, if for cervical cancer developing three vaccines (bi, tetra, and nonavalent) was possible, it will be feasible to create a vaccine against beta HPV types [20].
Given these recent data regarding skin cancer and the association with two potentially oncogenic viruses, wrese aim in this review toarchers present updates regarding detection methods, carcinogenetic mechanisms, and the availability of therapeutic vaccination for MCPyV and cutaneous HPV types.

4. MCV DNA Detection Assays

WeIt is analyzed the articles published in the last 5 years using the following keywords:”skin cancer Merkel cell polyomavirus detection assay”. From all 34 studies suitable for ourthe research, only 13 studies were selected. Since 2007, the detection methods for Merkel cell polyomavirus have evolved from serological diagnosis MCV-oncoprotein antibody detection [21], to testing by simultaneous complementary molecular techniques (classical and qPCR) [22[22][23][24][25][26][27],23,24,25,26,27], or by double analyzing MCC with molecular and immunohistochemical analyses [28]. This double testing underlines the necessity of confirmatory diagnosis by two different or complementary assays. An interesting study performed in France analyzed the circulating tumoral cells (CTCs) in blood samples for patients with MCC, and the reseauthorchers remarked on the tumor heterogeneity [29]. A very comprehensive study was the one realized at Bethesda, MD USA, in 2020, in which the reseauthorchers used deep sequencing with OncoPanel, a clinically implemented, next-generation sequencing assay targeting over 400 cancer-associated genes; they observed the value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC [30]. MCV DNA was detected in formalin-fixed and paraffin-embedded (FPPE) MCC samples, with different prevalence, from 10% up to 90%. The most common primers used were targeting the sT gene, VP1 and NCCR regions of the genome, and large T-antigen (LTAg) gene; the sequence of used primes are presented by the reseauthorchers [21,22,23,24,25,26,27,28,29,30,31,32,33][21][22][23][24][25][26][27][28][29][30][31][32][33].
Oncogenic transformation by MCPyV is hypothesized to require two events: the integration of the viral genome into the host genome, and the truncation of large Tantigen to render the viral genome incapable of replication. In the viral positive MCCs, the small T antigen has an important role in carcinogenesis: it is known to transform rat-1 fibroblasts in culture. Research carried out on transgenic mouse models has shown that the expression of small T antigen was transformative in various organ systems, including in the epidermis [15].
The carcinogenetic mechanisms identified from 2017 to 2022 were determined in different modalities, beginning with evaluating the MCPyV cultivation on cell lines, to assessing the expression of specific genes. The outcomes of the analyzed studies were correlated with possible future targeted therapies, including for metastatic MCC, and even with future vaccinations [34,35,36,37,38,39,40][34][35][36][37][38][39][40].
Skin biopsies from different skin cancer types were analyzed for the study of cutaneous HPV types, alone or in parallel, with samples from healthy skin as a comparison. The reseauthorchers have used only molecular biology techniques, beginning with classical PCR, followed by hybridization, qPCR, multiplex genotyping, and NGS. The primers used were targeting the E1 β-HPV gene fragment, two pairs of general degenerate primers CP65–70 (CP65/70 and CP66/69, consensus primer pair FAP (FAP59\FAP64) targeting the 5′end of the L1 ORF, FAP and PGMY-GP + primer systems, and E7 gene for HPV types. The analyzed studies found HPV types in different percentages in skin cancer and newly identified HPV types were reported. The authoresearchers underline the need of optimizing the sensitivities of the used assays and the necessity of confirmatory methods [41,42,43,44,45][41][42][43][44][45].​​​​​​​

References

  1. International Agency for Research on Cancer. A Review of Human Carcinogens: Biological Agents. In IARC Monographs of the Evaluation of Carcinogenic Risks to Humans; IARC: Lyon, France, 2012; ISBN 978-92-832-1319-2.
  2. Ferlay, J.; Ervik, M.; Lam, F.; Colombet, M.; Mery, L.; Piñeros, M.; Znaor, A.; Soerjomataram, I.; Bray, F. Global Cancer Observatory: Cancer Today. Available online: http://gco.iarc.fr/today/home (accessed on 11 March 2022).
  3. Porumb-Andrese, E.; Ursu, R.G.; Ivanov, I.; Caruntu, I.-D.; Porumb, V.; Ferariu, D.; Damian, C.; Ciobanu, D.; Terinte, C.; Iancu, L.S. The BRAF V600E Mutation Detection by Quasa Sensitive Real-Time PCR Assay in Northeast Romania Melanoma Patients. Appl. Sci. 2021, 11, 9511.
  4. Porumb-Andrese, E.; Scutariu, M.M.; Luchian, I.; Schreiner, T.G.; Mârţu, I.; Porumb, V.; Popa, C.G.; Sandu, D.; Ursu, R.G. Molecular Profile of Skin Cancer. Appl. Sci. 2021, 11, 9142.
  5. Becerril, S.; Corchado-Cobos, R.; García-Sancha, N.; Revelles, L.; Revilla, D.; Ugalde, T.; Román-Curto, C.; Pérez-Losada, J.; Cañueto, J. Viruses and Skin Cancer. Int. J. Mol. Sci. 2021, 22, 5399.
  6. Moens, U.; Calvignac-Spencer, S.; Lauber, C.; Ramqvist, T.; Feltkamp, M.C.W.; Daugherty, M.D.; Verschoor, E.J.; Ehlers, B. ICTV Virus Taxonomy Profile: Polyomaviridae. J. Gen. Virol. 2017, 98, 1159–1160.
  7. Taxonomy. Available online: https://talk.ictvonline.org/taxonomy/ (accessed on 12 April 2022).
  8. Buck, C.B.; Doorslaer, K.V.; Peretti, A.; Geoghegan, E.M.; Tisza, M.J.; An, P.; Katz, J.P.; Pipas, J.M.; McBride, A.A.; Camus, A.C.; et al. The Ancient Evolutionary History of Polyomaviruses. PLoS Pathog. 2016, 12, e1005574.
  9. Starrett, G.J.; Buck, C.B. The Case for BK Polyomavirus as a Cause of Bladder Cancer. Curr. Opin. Virol. 2019, 39, 8–15.
  10. Feng, H.; Shuda, M.; Chang, Y.; Moore, P.S. Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science 2008, 319, 1096–1100.
  11. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Malaria and Some Polyomaviruses (SV40, BK, JC and Merkel Cell Viruses). In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; IARC: Lyon, France, 2012; Volume 104.
  12. Bouvard, V.; Baan, R.A.; Grosse, Y.; Lauby-Secretan, B.; El Ghissassi, F.; Benbrahim-Tallaa, L.; Guha, N.; Straif, K.; WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of Malaria and of Some Polyomaviruses. Lancet Oncol. 2012, 13, 339–340.
  13. Becker, J.C.; Stang, A.; DeCaprio, J.A.; Cerroni, L.; Lebbé, C.; Veness, M.; Nghiem, P. Merkel Cell Carcinoma. Nat. Rev. Dis. Primers 2017, 3, 17077.
  14. Becker, J.C.; Stang, A.; Hausen, A.Z.; Fischer, N.; DeCaprio, J.A.; Tothill, R.W.; Lyngaa, R.; Hansen, U.K.; Ritter, C.; Nghiem, P.; et al. Epidemiology, Biology and Therapy of Merkel Cell Carcinoma: Conclusions from the EU Project IMMOMEC. Cancer Immunol. Immunother. 2018, 67, 341–351.
  15. Harms, P.W.; Harms, K.L.; Moore, P.S.; DeCaprio, J.A.; Nghiem, P.; Wong, M.K.K.; Brownell, I.; International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group. The Biology and Treatment of Merkel Cell Carcinoma: Current Understanding and Research Priorities. Nat. Rev. Clin. Oncol. 2018, 15, 763–776.
  16. Gheit, T. Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology. Front. Oncol. 2019, 9, 355.
  17. de Villiers, E.-M.; Fauquet, C.; Broker, T.R.; Bernard, H.-U.; zur Hausen, H. Classification of Papillomaviruses. Virology 2004, 324, 17–27.
  18. de Villiers, E.-M. Cross-Roads in the Classification of Papillomaviruses. Virology 2013, 445, 2–10.
  19. Venuti, A.; Lohse, S.; Tommasino, M.; Smola, S. Cross-Talk of Cutaneous Beta Human Papillomaviruses and the Immune System: Determinants of Disease Penetrance. Philos. Trans. R Soc. Lond. B Biol. Sci. 2019, 374, 20180287.
  20. Rollison, D.E.; Viarisio, D.; Amorrortu, R.P.; Gheit, T.; Tommasino, M. An Emerging Issue in Oncogenic Virology: The Role of Beta Human Papillomavirus Types in the Development of Cutaneous Squamous Cell Carcinoma. J. Virol. 2019, 93, e01003-18.
  21. Paulson, K.G.; Lewis, C.W.; Redman, M.W.; Simonson, W.T.; Lisberg, A.; Ritter, D.; Morishima, C.; Hutchinson, K.; Mudgistratova, L.; Blom, A.; et al. Viral Oncoprotein Antibodies as a Marker for Recurrence of Merkel Cell Carcinoma: A Prospective Validation Study. Cancer 2017, 123, 1464–1474.
  22. Prezioso, C.; Carletti, R.; Obregon, F.; Piacentini, F.; Manicone, A.M.; Soda, G.; Moens, U.; Di Gioia, C.; Pietropaolo, V. Evaluation of Merkel Cell Polyomavirus DNA in Tissue Samples from Italian Patients with Diagnosis of MCC. Viruses 2021, 13, 61.
  23. Costa, P.V.A.; Ishiy, P.S.; Urbano, P.R.P.; Romano, C.M.; Tyring, S.K.; Oliveira, W.R.P.; Festa-Neto, C. Identification of Polyomaviruses in Skin Cancers. Intervirology 2021, 64, 119–125.
  24. Motavalli Khiavi, F.; Nasimi, M.; Rahimi, H. Merkel Cell Polyomavirus Gene Expression and Mutational Analysis of Large Tumor Antigen in Non-Merkel Cell Carcinoma Tumors of Iranian Patients. Public Health Genom. 2020, 23, 210–217.
  25. Neto, C.F.; Oliveira, W.R.P.; Costa, P.V.A.; Cardoso, M.K.; Barreto, P.G.; Romano, C.M.; Urbano, P.R. The First Observation of the Association of Merkel Cell Polyomavirus and Merkel Cell Carcinoma in Brazil. Int. J. Dermatol. 2019, 58, 703–706.
  26. Kervarrec, T.; Samimi, M.; Gaboriaud, P.; Gheit, T.; Beby-Defaux, A.; Houben, R.; Schrama, D.; Fromont, G.; Tommasino, M.; Le Corre, Y.; et al. Detection of the Merkel Cell Polyomavirus in the Neuroendocrine Component of Combined Merkel Cell Carcinoma. Virchows Arch. 2018, 472, 825–837.
  27. Álvarez-Argüelles, M.E.; Melón, S.; Rojo, S.; Fernandez-Blázquez, A.; Boga, J.A.; Palacio, A.; Vivanco, B.; de Oña, M. Detection and Quantification of Merkel Cell Polyomavirus. Analysis of Merkel Cell Carcinoma Cases from 1977 to 2015. J. Med. Virol. 2017, 89, 2224–2229.
  28. Ungari, M.; Manotti, L.; Tanzi, G.; Varotti, E.; Ferrero, G.; Gusolfino, M.D.; Trombatore, M.; Cavazzuti, L.; Tolomini, M. NeuN, a DNA-Binding Neuron-Specific Protein Expressed by Merkel Cell Carcinoma: Analysis of 15 Cases. Pathologica 2021, 113, 421–426.
  29. Boyer, M.; Cayrefourcq, L.; Garima, F.; Foulongne, V.; Dereure, O.; Alix-Panabières, C. Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma. Sci. Rep. 2020, 10, 1612.
  30. Starrett, G.J.; Thakuria, M.; Chen, T.; Marcelus, C.; Cheng, J.; Nomburg, J.; Thorner, A.R.; Slevin, M.K.; Powers, W.; Burns, R.T.; et al. Clinical and Molecular Characterization of Virus-Positive and Virus-Negative Merkel Cell Carcinoma. Genome Med. 2020, 12, 30.
  31. Toptan, T.; Cantrell, P.S.; Zeng, X.; Liu, Y.; Sun, M.; Yates, N.A.; Chang, Y.; Moore, P.S. Proteomic Approach to Discover Human Cancer Viruses from Formalin-Fixed Tissues. JCI Insight 2020, 5, 143003.
  32. Wang, L.; Harms, P.W.; Palanisamy, N.; Carskadon, S.; Cao, X.; Siddiqui, J.; Patel, R.M.; Zelenka-Wang, S.; Durham, A.B.; Fullen, D.R.; et al. Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay. Clin. Cancer Res. 2017, 23, 5622–5630.
  33. Arvia, R.; Sollai, M.; Pierucci, F.; Urso, C.; Massi, D.; Zakrzewska, K. Droplet Digital PCR (DdPCR) vs Quantitative Real-Time PCR (QPCR) Approach for Detection and Quantification of Merkel Cell Polyomavirus (MCPyV) DNA in Formalin Fixed Paraffin Embedded (FFPE) Cutaneous Biopsies. J. Virol. Methods 2017, 246, 15–20.
  34. Krump, N.A.; Wang, R.; Liu, W.; Yang, J.F.; Ma, T.; You, J. Merkel Cell Polyomavirus Infection Induces an Antiviral Innate Immune Response in Human Dermal Fibroblasts. J. Virol. 2021, 95, e0221120.
  35. Guadagni, S.; Farina, A.R.; Cappabianca, L.A.; Sebastiano, M.; Maccarone, R.; Zelli, V.; Clementi, M.; Chiominto, A.; Bruera, G.; Ricevuto, E.; et al. Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ Exon 6–7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A. Int. J. Mol. Sci. 2020, 21, 8222.
  36. Zhao, J.; Jia, Y.; Shen, S.; Kim, J.; Wang, X.; Lee, E.; Brownell, I.; Cho-Vega, J.H.; Lewis, C.; Homsi, J.; et al. Merkel Cell Polyomavirus Small T Antigen Activates Noncanonical NF-ΚB Signaling to Promote Tumorigenesis. Mol. Cancer Res. 2020, 18, 1623–1637.
  37. Nwogu, N.; Ortiz, L.E.; Whitehouse, A.; Kwun, H.J. Merkel Cell Polyomavirus Small Tumor Antigen Activates Matrix Metallopeptidase-9 Gene Expression for Cell Migration and Invasion. J. Virol. 2020, 94, e00786-20.
  38. Gupta, P.; Shahzad, N.; Harold, A.; Shuda, M.; Venuti, A.; Romero-Medina, M.C.; Pacini, L.; Brault, L.; Robitaille, A.; Taverniti, V.; et al. Merkel Cell Polyomavirus Downregulates N-Myc Downstream-Regulated Gene 1, Leading to Cellular Proliferation and Migration. J. Virol. 2020, 94, e00899-19.
  39. Longino, N.V.; Yang, J.; Iyer, J.G.; Ibrani, D.; Chow, I.-T.; Laing, K.J.; Campbell, V.L.; Paulson, K.G.; Kulikauskas, R.M.; Church, C.D.; et al. Human CD4+ T Cells Specific for Merkel Cell Polyomavirus Localize to Merkel Cell Carcinomas and Target a Required Oncogenic Domain. Cancer Immunol. Res. 2019, 7, 1727–1739.
  40. Wu, J.H.; Narayanan, D.; Limmer, A.L.; Simonette, R.A.; Rady, P.L.; Tyring, S.K. Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response. Intervirology 2019, 62, 96–100.
  41. Sitarz, K.; Kopec, J.; Szostek, S.; Sulowicz, J. Incidence of Betapapillomaviruses in the Tumour and Perilesional Healthy Skin in Patients with Basal Cell Carcinoma Depending on Sex, Age, Hair Colour, Tumour Subtype, Its Location and Dissemination. Postepy Derm. Alergol. 2021, 38, 866–872.
  42. Kopeć, J.; Szostek, S.; Sułowicz, J.; Zawilińska, B. Comparison and Evaluation of Three Different Molecular Methods for Detection of Human Betapapillomaviruses in Skin Biopsies from Patients with Nonmelanoma Skin Cancer and Precancerous Lesions. Acta Biochim. Pol. 2020, 67, 189–195.
  43. Galati, L.; Brancaccio, R.N.; Robitaille, A.; Cuenin, C.; Luzi, F.; Fiorucci, G.; Chiantore, M.V.; Marascio, N.; Matera, G.; Liberto, M.C.; et al. Detection of Human Papillomaviruses in Paired Healthy Skin and Actinic Keratosis by next Generation Sequencing. Papillomavirus Res. 2020, 9, 100196.
  44. Nguyen, C.V.; He, Q.; Rady, P.L.; Tyring, S.K.; Miller, D.D.; Rubin, N.; Kovarik, C.L. Presence of Human Papillomavirus DNA in Voriconazole-Associated Cutaneous Squamous Cell Carcinoma. Int. J. Dermatol. 2020, 59, 595–598.
  45. Rollison, D.E.; Schell, M.J.; Fenske, N.A.; Cherpelis, B.; Messina, J.L.; Giuliano, A.R.; Epling-Burnette, P.K.; Hampras, S.S.; Amorrortu, R.P.; Balliu, J.; et al. Cutaneous Viral Infections Across 2 Anatomic Sites Among a Cohort of Patients Undergoing Skin Cancer Screening. J. Infect. Dis. 2019, 219, 711–722.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Academic Video Service
Feedback