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Adèle C. Green - One of the best experts on this subject based on the ideXlab platform.
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A case-control study of Betapapillomavirus infection and cutaneous squamous cell carcinoma in organ transplant recipients.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011Co-Authors: Charlotte M. Proby, Mariet C W Feltkamp, Rachel E. Neale, Adèle C. Green, M.n.c. De Koning, Sylvie Euvrard, Catherine A. Harwood, Luigi Naldi, Gianpaolo Tessari, W. G. V. QuintAbstract:We examined the association between Betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.
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the association between cutaneous squamous cell carcinoma and Betapapillomavirus seropositivity a cohort study
Cancer Epidemiology Biomarkers & Prevention, 2011Co-Authors: Elsemieke I. Plasmeijer, Mariet C W Feltkamp, Nirmala Pandeya, Adèle C. Green, Michael Pawlita, Tim Waterboer, Peter Orourke, Rachel E. NealeAbstract:Background: It is currently unclear whether Betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Methods: Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. Results: SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Conclusions: Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. Impact: This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case–control studies. Cancer Epidemiol Biomarkers Prev; 20(6); 1171–7. ©2011 AACR .
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The Association between Cutaneous Squamous Cell Carcinoma and Betapapillomavirus Seropositivity: a Cohort Study
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 2011Co-Authors: Elsemieke I. Plasmeijer, Mariet C W Feltkamp, Nirmala Pandeya, Adèle C. Green, Peter O'rourke, Michael Pawlita, Tim Waterboer, Rachel E. NealeAbstract:It is currently unclear whether Betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case--control studies. ©2011 AACR.
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Multicenter Study of the Association between Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma
Cancer research, 2010Co-Authors: Jan Nico Bouwes Bavinck, Rachel E. Neale, Adèle C. Green, Damiano Abeni, Maurits N. C. De Koning, Ingo Nindl, Sylvie Euvrard, Catherine A. Harwood, Luigi Naldi, Michael PawlitaAbstract:Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case-control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case-control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma.
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An analysis of clustering of Betapapillomavirus antibodies.
Journal of General Virology, 2010Co-Authors: Kylie-ann Mallitt, Mariet C W Feltkamp, Adèle C. Green, M.n.c. De Koning, Peter O'rourke, J.n. Bouwes Bavinck, Damiano Abeni, W. G. V. Quint, Kristina M. Michael, Michael PawlitaAbstract:Betapapillomaviruses (βPVs) may contribute to the aetiology of cutaneous squamous cell carcinoma. However, no high-risk types have yet been identified, possibly because the high frequency of co-infection prevents a straightforward analysis of the independent effects of individual viruses. This study aimed to determine whether specific virus types were more likely to co-occur than others, thereby reducing the number of parameters needed in statistical models. Antibody data were analysed from controls who participated in case–control studies in The Netherlands, Italy and Australia and from participants in the German Nutrition Survey. Cluster analysis and two ordination techniques were used to identify patterns. Evidence of clustering was found only according to the number of viruses to which antibodies were detected. The lack of clustering of specific viral types identified suggests that if there are βPV types that are independently related to skin carcinogenesis, they are unlikely to be identified using standard epidemiological methods.
Baki Akgül - One of the best experts on this subject based on the ideXlab platform.
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BetaHPV E6 and E7 colocalize with NuMa in dividing keratinocytes
Virus Genes, 2019Co-Authors: Evelyn Oswald, Martin Hufbauer, Baki Akgül, Matthias Kirschberg, François Aubin, Angel Alonso, Eeva AuvinenAbstract:Human papillomaviruses (HPVs) of genus Betapapillomavirus (betaHPV) are implicated in skin carcinogenesis, but their exact role in keratinocyte transformation is poorly understood. We show an interaction of HPV5 and HPV8 oncoproteins E6 and E7 with the nuclear mitotic apparatus protein 1 (NuMA). Binding of E6 or E7 to NuMA induces little aneuploidy, cell cycle alterations, or aberrant centrosomes. Intracellular localization of NuMA is not altered by E6 and E7 expression in 2D cultures. However, the localization profile is predominantly cytoplasmic in 3D organotypic skin models. Both viral proteins colocalize with NuMA in interphase cells, while only E7 colocalizes with NuMA in mitotic cells. Intriguingly, a small subset of cells shows E7 at only one spindle pole, whereas NuMA is present at both poles. This dissimilar distribution of E7 at the spindle poles may alter cell differentiation, which may in turn be relevant for betaHPV-induced skin carcinogenesis.
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Molecular Mechanisms of Human Papillomavirus Induced Skin Carcinogenesis
Viruses, 2017Co-Authors: Martin Hufbauer, Baki AkgülAbstract:Infection of the cutaneous skin with human papillomaviruses (HPV) of genus Betapapillomavirus (βHPV) is associated with the development of premalignant actinic keratoses and squamous cell carcinoma. Due to the higher viral loads of βHPVs in actinic keratoses than in cancerous lesions, it is currently discussed that these viruses play a carcinogenic role in cancer initiation. In vitro assays performed to characterize the cell transforming activities of high-risk HPV types of genus alphapapillomavirus have markedly contributed to the present knowledge on their oncogenic functions. However, these assays failed to detect oncogenic functions of βHPV early proteins. They were not suitable for investigations aiming to study the interactive role of βHPV positive epidermis with mesenchymal cells and the extracellular matrix. This review focuses on βHPV gene functions with special focus on oncogenic mechanisms that may be relevant for skin cancer development.
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The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8.
The Journal of general virology, 2015Co-Authors: Sandra Heuser, Martin Hufbauer, Herbert Pfister, Benjamin L. Marx, Ali Tok, Slawomir Majewski, Baki AkgülAbstract:Infection with viruses of the genus Betapapillomavirus, β-human papillomaviruses (β-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins β-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that β-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of β-catenin was elevated, no signs of β-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of β-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that β-catenin and ZO-1 are direct targets of E7 of the oncogenic β-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.
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Expression of Betapapillomavirus oncogenes increases the number of keratinocytes with stem cell-like properties.
Journal of virology, 2013Co-Authors: Martin Hufbauer, Herbert Pfister, Alan Storey, Marisa Gariglio, Adrian Biddle, Cinzia Borgogna, John Doorbar, Ian C. Mackenzie, Baki AkgülAbstract:Human papillomaviruses (HPV) of genus Betapapillomavirus (betaPV) are associated with nonmelanoma skin cancer development in epidermodysplasia verruciformis (EV) and immunosuppressed patients. Epidemiological and molecular studies suggest a carcinogenic activity of betaPV during early stages of cancer development. Since viral oncoproteins delay and perturb keratinocyte differentiation, they may have the capacity to either retain or confer a "stem cell-like" state on oncogene-expressing cells. The aim of this study was to determine (i) whether betaPV alters the expression of cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), that have been associated with epithelial stemness, and (ii) whether this confers functional stem cell-like properties to human cutaneous keratinocytes. Fluorescence-activated cell sorter (FACS) analysis revealed an increase in the number of cells with high CD44 and EpCAM expression in keratinocyte cultures expressing HPV type 8 (HPV8) oncogenes E2, E6, and E7. Particularly through E7 expression, a distinct increase in clonogenicity and in the formation and size of tumor spheres was observed, accompanied by reduction of the epithelial differentiation marker Calgranulin B. These stem cell-like properties could be attributed to the pool of CD44(high) EpCAM(high) cells, which was increased within the E7 cultures of HPV5, -8, and -20. Enhanced EpCAM levels were present in organotypic skin cultures of primary keratinocytes expressing E7 of the oncogenic HPV types HPV5, -8, and -16 and in clinical samples from EV patients. In conclusion, our data show that betaPV may increase the number of stem cell-like cells present during early carcinogenesis and thus enable the persistence and accumulation of DNA damage necessary to generate malignant stem cells.
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Human Papillomavirus Type 8 E6 Oncoprotein Inhibits Transcription of the PDZ Protein Syntenin-2
Journal of virology, 2012Co-Authors: Daliborka Lazić, Mariet C W Feltkamp, Siamaque Kazem, Martin Hufbauer, Herbert Pfister, Paola Zigrino, Stephanie Buchholz, Cornelia Mauch, Gertrud Steger, Baki AkgülAbstract:The E6 proteins from high-risk alpha human papillomavirus (HPV) types (e.g., HPV16) are characterized by the presence of a PDZ-binding motif through which they interact with a number of cellular PDZ domain-containing substrates and cooperate in their degradation. The ability of these E6 proteins to bind to PDZ domain proteins correlates with the oncogenic potential of the virus. The E6 proteins of oncogenic HPV from the genus Betapapillomavirus (betaPV, e.g., HPV8) do not encode a PDZ-binding motif. We found that the PDZ domain protein syntenin-2 is transcriptionally downregulated in primary human epidermal keratinocytes (PHEK) by HPV8 E6. The mRNA levels of the known HPV16 E6 PDZ protein targets Dlg, Scribble, Magi-1, Magi-3, PSD95, and Mupp1 were not changed by HPV8 E6. Decreased protein levels of syntenin-2 were observed in cell extracts from PHEK expressing HPV5, -8, -16, -20, and -38 E6 but not in HPV1 and -4 E6-positive keratinocytes. Surprisingly, HPV16 E6 also repressed transcription of syntenin-2 but with a much lower efficiency than HPV8 E6. In healthy human skin, syntenin-2 expression is localized in suprabasal epidermal layers. In organotypic skin cultures, the differentiation-dependent expression of syntenin-2 was absent in HPV8 E6- and E6E7-expressing cells. In basal cell carcinomas of the skin, syntenin-2 was not detectable, whereas in squamous cell carcinomas, expression was located in differentiated areas. Short hairpin RNA-mediated knockdown of syntenin-2 led to an inhibition of differentiation and an increase in the proliferation capacity in PHEK. These results identified syntenin-2 as the first PDZ domain protein controlled by HPV8 and HPV16 at the mRNA level.
Herbert Pfister - One of the best experts on this subject based on the ideXlab platform.
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The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8.
The Journal of general virology, 2015Co-Authors: Sandra Heuser, Martin Hufbauer, Herbert Pfister, Benjamin L. Marx, Ali Tok, Slawomir Majewski, Baki AkgülAbstract:Infection with viruses of the genus Betapapillomavirus, β-human papillomaviruses (β-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins β-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that β-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of β-catenin was elevated, no signs of β-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of β-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that β-catenin and ZO-1 are direct targets of E7 of the oncogenic β-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.
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association between Betapapillomavirus seropositivity and keratinocyte carcinoma prospects for prophylactic vaccination
Journal of Investigative Dermatology, 2015Co-Authors: Herbert PfisterAbstract:In this issue, Genders et al. (2015) demonstrate in a cohort of organ transplant recipients that Betapapillomavirus seropositivity around transplantation significantly increases the risk of developing keratinocyte carcinomas. These results further substantiate an etiologic role of Betapapillomaviruses in skin cancer and raise prospects of anti-viral immunotherapy.
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Association between Betapapillomavirus Seropositivity and Keratinocyte Carcinoma—Prospects for Prophylactic Vaccination?
The Journal of investigative dermatology, 2015Co-Authors: Herbert PfisterAbstract:In this issue, Genders et al. (2015) demonstrate in a cohort of organ transplant recipients that Betapapillomavirus seropositivity around transplantation significantly increases the risk of developing keratinocyte carcinomas. These results further substantiate an etiologic role of Betapapillomaviruses in skin cancer and raise prospects of anti-viral immunotherapy.
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Tumor prevention in HPV8 transgenic mice by HPV8-E6 DNA vaccination
Medical Microbiology and Immunology, 2014Co-Authors: Gian Paolo Marcuzzi, Lutz Gissmann, Sabine Awerkiew, Martin Hufbauer, Lysann Schädlich, Sabine Eming, Herbert PfisterAbstract:The genus beta human papillomavirus 8 (HPV8) is involved in the development of cutaneous squamous cell carcinomas (SCCs) in individuals with epidermodysplasia verruciformis. Immunosuppressed transplant recipients are prone to harbor particularly high Betapapillomavirus DNA loads, which may contribute to their highly increased risk of SCC. Tumor induction in HPV8 transgenic mice correlates with increased expression of viral oncogenes E6 and E2. In an attempt to prevent skin tumor development, we evaluated an HPV8-E6-DNA vaccine, which was able to stimulate a detectable HPV8-E6-specific cell-mediated immune response in 8/15 immunized mice. When skin of HPV8 transgenic mice was grafted onto non-transgenic littermates, the grafted HPV8 transgenic tissue was not rejected and papillomas started to grow within 14 days all over the transplant of 9/9 non-vaccinated and 7/15 not successfully vaccinated mice. In contrast, no papillomas developed in 6/8 successfully vaccinated mice. In the other two of these eight mice, a large ulcerative lesion developed within the initial papilloma growth or papilloma development was highly delayed. As the vaccine completely or partially prevented papilloma development without rejecting the transplanted HPV8 positive skin, the immune system appears to attack only keratinocytes with increased levels of E6 protein, which would give rise to papillomas.
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Expression of Betapapillomavirus oncogenes increases the number of keratinocytes with stem cell-like properties.
Journal of virology, 2013Co-Authors: Martin Hufbauer, Herbert Pfister, Alan Storey, Marisa Gariglio, Adrian Biddle, Cinzia Borgogna, John Doorbar, Ian C. Mackenzie, Baki AkgülAbstract:Human papillomaviruses (HPV) of genus Betapapillomavirus (betaPV) are associated with nonmelanoma skin cancer development in epidermodysplasia verruciformis (EV) and immunosuppressed patients. Epidemiological and molecular studies suggest a carcinogenic activity of betaPV during early stages of cancer development. Since viral oncoproteins delay and perturb keratinocyte differentiation, they may have the capacity to either retain or confer a "stem cell-like" state on oncogene-expressing cells. The aim of this study was to determine (i) whether betaPV alters the expression of cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), that have been associated with epithelial stemness, and (ii) whether this confers functional stem cell-like properties to human cutaneous keratinocytes. Fluorescence-activated cell sorter (FACS) analysis revealed an increase in the number of cells with high CD44 and EpCAM expression in keratinocyte cultures expressing HPV type 8 (HPV8) oncogenes E2, E6, and E7. Particularly through E7 expression, a distinct increase in clonogenicity and in the formation and size of tumor spheres was observed, accompanied by reduction of the epithelial differentiation marker Calgranulin B. These stem cell-like properties could be attributed to the pool of CD44(high) EpCAM(high) cells, which was increased within the E7 cultures of HPV5, -8, and -20. Enhanced EpCAM levels were present in organotypic skin cultures of primary keratinocytes expressing E7 of the oncogenic HPV types HPV5, -8, and -16 and in clinical samples from EV patients. In conclusion, our data show that betaPV may increase the number of stem cell-like cells present during early carcinogenesis and thus enable the persistence and accumulation of DNA damage necessary to generate malignant stem cells.
Ola Forslund - One of the best experts on this subject based on the ideXlab platform.
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Phylogenetic tree for HPV154 and related papillomaviruses.
2014Co-Authors: Agustín Enrique Ure, Ola ForslundAbstract:Ninety one complete genomes were analyzed, including all gammapapillomaviruses as well as related genera but closer than Betapapillomaviruses. HPV154 is indicated with an arrow. The tree was obtained by the maximum likelihood approach using RAxML software and rooted with the Betapapillomavirus HPV5 and HPV9. Bootstrap support values are indicated in each branch as percentages. Genera are indicated at the rightmost side, while species of γ-PVs are to the right of brackets. The dotted key to the left of γ-PV11* shows species suggested in this work. The bar indicates the number of substitutions per site. * Proposed category and pending approval by ICTV. †Putative novel species. ‡: Uncloned HPV genome (not official type). The following species are represented by the types included in the tree: AsPV1, Apodemus sylvaticus papillomavirus 1; BPV, Bos taurus papillomavirus spp.; ChPV1, Capra hircus papillomavirus 1; CPV, Canis familiaris papillomavirus spp.; DdPV1, Delphinus delphis papillomavirus 1; HPV, Gammapapillomavirus spp.; McPV2, Mastomys coucha Papillomavirus 2; PphPV, Phocoena phocoena papillomavirus spp.; PsPV1, Phocoena spinipinnis Papillomavirus 1; TtPV, Tursiops truncatus Papillomavirus spp.
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Diversity of human papillomaviruses in skin lesions.
Virology, 2013Co-Authors: Johanna Ekström, Ola Forslund, Davit Bzhalava, Emilie Hultin, Laila Sara Arroyo Mühr, Anna Söderlund-strand, Peter Nordin, Bo Stenquist, John Paoli, Joakim DillnerAbstract:Pools of frozen biopsies from patients with squamous cell carcinoma (SCC) (n=29) actinic keratosis (AK) (n=31), keratoacanthoma (n=91) and swab samples from 84 SCCs and 91 AKs were analysed with an extended HPV general primer PCR and high-throughput sequencing of amplimers. We found 273 different HPV isolates (87 known HPV types, 139 previously known HPV sequences (putative types) and 47 sequences from novel putative HPV types). Among the new sequences, five clustered in genus Betapapillomavirus and 42 in genus Gammapapillomavirus. Resequencing of the three pools between 21 to 70 times resulted in the detection of 283 different known or putative HPV types, with 156 different sequences found in only one of the pools. Type-specific PCRs for 37 putative types from an additional 296 patients found only two of these putative types. In conclusion, skin lesions contain a large diversity of HPV types, but most appeared to be rare infections.
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The Nasal Mucosa Contains a Large Spectrum of Human Papillomavirus Types from the Betapapillomavirus and Gammapapillomavirus Genera
The Journal of infectious diseases, 2013Co-Authors: Ola Forslund, Hanna K Johansson, Klaus Gregaard Madsen, Kristian KofoedAbstract:Background. Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples. Methods. Nasal samples and oral samples were obtained from 312 volunteer Danish healthcare staff (240 women and 72 men), among whom the mean age was 42 years. A total of 311 oral samples and 304 nasal samples were eligible for HPV DNA analysis. HPV types were detected by use of polymerase chain reactions with modified general primers (MGP) and Forslund-Antonsson primers (FAP) and identified by Luminex (for types detected by MGP PCR) or direct sequencing or cloning before sequencing (for types detected by FAP PCR). Results. HPV DNA was detected in 6% of the oral samples and 50% of the nasal samples. Seventy-five diverse HPV types or putative HPV types were identified. HPV types within the Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus genera were detected in 3%, 31%, and 23% of the nasal samples, respectively. A putative subtype of HPV76, originally isolated from a feline oral squamous cell carcinoma, was detected in 7 nasal samples. Conclusion. A large spectrum of HPV types from Betapapillomavirus and Gammapapillomavirus have tropism for the nasal mucosa. The implication of the relatively high prevalence of these viruses in the nasal mucosa is unknown.
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Metagenomic sequencing of "HPV-negative" condylomas detects novel putative HPV types.
Virology, 2013Co-Authors: Hanna K Johansson, Joakim Dillner, Davit Bzhalava, Johanna Ekström, Emilie Hultin, Ola ForslundAbstract:Condylomas are caused by human papillomavirus (HPV), but may in rare cases be "negative for HPV" by PCR. Metagenomic sequencing can be used for an unbiased assessment of the presence of virus. Ten swab sample pools, each containing four cases of "HPV-negative" condylomas, were subjected to metagenomic sequencing. One pool contained Molluscum contagiosum. Five pools contained HPV, of which three pools contained novel putative HPV-types. The 12 samples in these three pools were sequenced individually. Six of these contained HPV and two contained Molluscum contagiosum. Altogether, 1337 HPV-related reads were detected, representing 23 novel putative Gammapapillomaviruses, 10 established HPV types (genital HPV types 6, 57, 58 and 66, Betapapillomavirus types 5, 105, 124, and Gammapapillomavirus types 50, 130, 150) and two described HPV sequences (KC7 and FA69). Complete genomes of Gammapillomavirus FA69 and SE87 were compiled. Metagenomic sequencing reveals that seemingly "HPV-negative" condylomas contain known and previously unknown HPV types.
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Serological relationship between cutaneous human papillomavirus types 5, 8 and 92.
The Journal of general virology, 2009Co-Authors: Alessandra Handisurya, Ola Forslund, Ratish Gambhira, Christina Schellenbacher, Saeed Shafti-keramat, Michel Favre, Reinhard KirnbauerAbstract:Evidence of a possible association of cutaneous human papillomavirus (HPV) types, especially members of the genus Betapapillomavirus, and the development of non-melanoma skin cancer (NMSC) is accumulating. Vaccination with virus-like particles (VLPs) consisting of self-assembled L1, the major capsid protein, has been introduced to control anogenital HPV infection. This study examined the serological relationship between Betapapillomavirus (beta-PV) types 5 and 8 and the new type HPV-92, which has recently been isolated from a basal cell carcinoma containing a high number of viral genomes. Following expression by recombinant baculoviruses, the L1 protein of HPV-92 self-assembled into VLPs that elicited high-titre antibodies after immunization, similar to VLPs from HPV-5 and -8. Haemagglutination inhibition (HAI) assays were used as a surrogate method for the detection of virion-neutralizing antibodies, which correlates with protection from infection. Antisera raised against HPV-5 and -8 VLPs displayed HAI activity not only against the homologous type, but also against heterologous HPV types 5, 8 and 92, whereas HAI activity of antisera against HPV-92 VLP was restricted to the homologous type. The results of neutralization assays using HPV-5 pseudovirions were consistent with those from HAI assays. Cross-neutralizing immune responses by VLP vaccination against heterologous HPV types may provide broader protection against the multiplicity of HPV types detected in NMSC. If a close link to HPV infection can be conclusively established, these results may provide a basis for further evaluation of VLPs of beta-PVs as candidates for a prophylactic skin-type HPV vaccine, aimed at reducing the incidence of NMSC.
Rachel E. Neale - One of the best experts on this subject based on the ideXlab platform.
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A case-control study of Betapapillomavirus infection and cutaneous squamous cell carcinoma in organ transplant recipients.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011Co-Authors: Charlotte M. Proby, Mariet C W Feltkamp, Rachel E. Neale, Adèle C. Green, M.n.c. De Koning, Sylvie Euvrard, Catherine A. Harwood, Luigi Naldi, Gianpaolo Tessari, W. G. V. QuintAbstract:We examined the association between Betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.
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the association between cutaneous squamous cell carcinoma and Betapapillomavirus seropositivity a cohort study
Cancer Epidemiology Biomarkers & Prevention, 2011Co-Authors: Elsemieke I. Plasmeijer, Mariet C W Feltkamp, Nirmala Pandeya, Adèle C. Green, Michael Pawlita, Tim Waterboer, Peter Orourke, Rachel E. NealeAbstract:Background: It is currently unclear whether Betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Methods: Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. Results: SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Conclusions: Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. Impact: This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case–control studies. Cancer Epidemiol Biomarkers Prev; 20(6); 1171–7. ©2011 AACR .
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The Association between Cutaneous Squamous Cell Carcinoma and Betapapillomavirus Seropositivity: a Cohort Study
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 2011Co-Authors: Elsemieke I. Plasmeijer, Mariet C W Feltkamp, Nirmala Pandeya, Adèle C. Green, Peter O'rourke, Michael Pawlita, Tim Waterboer, Rachel E. NealeAbstract:It is currently unclear whether Betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case--control studies. ©2011 AACR.
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Multicenter Study of the Association between Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma
Cancer research, 2010Co-Authors: Jan Nico Bouwes Bavinck, Rachel E. Neale, Adèle C. Green, Damiano Abeni, Maurits N. C. De Koning, Ingo Nindl, Sylvie Euvrard, Catherine A. Harwood, Luigi Naldi, Michael PawlitaAbstract:Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case-control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case-control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3-5.8) and Italy (OR = 1.7; 95% CI 0.79-3.6), but not in Australia (OR = 0.91; 95% CI 0.53-1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4-3.3), the Netherlands (OR = 2.0; 95% CI 1.2-3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94- 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma.
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Lack of association between the presence and persistence of Betapapillomavirus DNA in eyebrow hairs and Betapapillomavirus L1 antibodies in serum.
Journal of General Virology, 2010Co-Authors: Elsemieke I. Plasmeijer, Rachel E. Neale, Kylie-ann Mallitt, Peter O'rourke, Michael Pawlita, Maurits N. C. De Koning, Wim Quint, Petra G. Buettner, Tim Waterboer, Adèle C. GreenAbstract:Betapapillomavirus (βPV) DNA and seroresponses are highly prevalent in the general population and both are frequently used as infection markers in epidemiological studies to elucidate an association with cutaneous squamous cell carcinoma (SCC). Little is known about the natural history of βPV infection and the aspects of infection that drive antibody responses. To investigate the relationship between these markers, this study assessed whether the presence or persistence of βPV DNA in eyebrow hairs and L1 antibodies of the same βPV type co-occurred more frequently than would be expected by chance in both a cross-sectional assessment and a longitudinal study. βPV DNA in plucked eyebrow hairs and L1 antibodies in serum were measured in 416 participants of the Australian community-based Nambour Skin Cancer Study in 1996. Similar data were available for a subset of 148 participants in 2003. Observed co-occurrence of βPV DNA and antibodies was compared with expected values based on prevalence. A case-wise concordance index was used to calculate the overall concordance of βPV DNA and antibodies of the same type. No significant associations were found between the presence or persistence of βPV DNA and antibody responses. The age and sex of the host did not influence the association, and nor did SCC status or a history of sunburns. It was concluded that βPV antibody responses in adults are not primarily driven by βPV infection as measured in eyebrow hairs. Other factors, such as viral load, may play a more pivotal role in the induction of detectable seroresponses.