Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland

Mackintosh, Lorna; Koning, Maurits N.C. de; Quint, Wim; Schegget, Jan ter; Morgan, Iain M.; Herd, R. M.; Campo, M. Saveria

doi:10.1111/j.1365-2133.2009.09146.x

Cited by 32 publications

(32 citation statements)

References 31 publications

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“…14,23,24,30–38 SCC from immunosuppressed patients are more likely to carry HPV than SCC from immunocompetent patients (pooled ES 3.01, 95%CI 2.00–4.52, p<0.0001). There was minimal evidence of heterogeneity (I 2 =28.4%, Q = 15.37 (d.f.…”

Section: Resultsmentioning

confidence: 99%

Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis

Wang

Aldabagh

et al. 2014

Journal of the American Academy of Dermatology

149

127

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Background The role of HPV in cutaneous squamous cell carcinoma (cuSCC) is not well defined, with past studies showing conflicting results. Objective We sought to determine if there is a significant association between HPV and cuSCC and whether cuSCC from immunosuppressed patients are more likely to carry HPV than cuSCC from immunocompetent patients. Methods We performed a systematic review and abstracted data from articles that included: skin samples by biopsy, HPV detection by PCR, and a minimum of 10 cases and 10 controls. Pooled effect size and 95% confidence intervals were calculated using random effects meta-analysis using the inverse variance method. Results cuSCC were more likely to carry HPV than normal skin (pooled ES 3.43, 95% CI 1.97–5.98, p<0.0001) in all patients. An increase in HPV prevalence was found in tumors from immunosuppressed patients compared to immunocompetent patients (pooled ES 3.01, 95%CI 2.00–4.52, p<0.0001). Limitations The greatest limitation is the heterogeneity of the studies included. The association of higher HPV prevalence in SCC compared to normal skin does not imply causality. Conclusion These results contribute to evidence that HPV is associated with cuSCC. Higher HPV burden in tumors from immunosuppressed patients compared to immunocompetent patients may have therapeutic implications.

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Section: Resultsmentioning

confidence: 99%

Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis

Wang

Aldabagh

et al. 2014

Journal of the American Academy of Dermatology

149

127

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“…Seroepidemiological studies have associated skin cancer in organ transplant recipients with the presence of anti-b-HPV antibodies, and PCR-based studies have identified b-HPV DNA in over 80% of skin tumors from these patients. 22,[35][36][37][38][39][40][41][42][43] Despite these findings, a causal role of these viruses has been difficult to verify because of their ubiquitous prevalence in the general population and their absence in some cancers. 25,44 The major weakness of the available studies is that the proposed association is mostly based on the presence of viral DNA in tumor tissues or positive antibody responses.…”

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confidence: 99%

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

et al. 2014

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The aim of this study was to determine whether detection of b-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that b-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the b-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that b-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion. Modern Pathology (2014) 27, 1101-1115; doi:10.1038/modpathol.2013.240; published online 3 January 2014Keywords: b-HPV; immunosuppression; kidney transplant recipients; skin cancer; viral life cycle Solid organ transplantation is a treatment offered to an increasing number of patients with end-stage organ diseases. Although lifesaving, organ transplantation is associated with an overall three-to fivefold increased risk of malignancies. 1-4 Most of these cancers are caused by reactivated viruses whose oncogenic potential is suppressed by immunological reactions in healthy individuals, like Epstein-Barr virus-associated B-cell lymphomas, Kaposi's sarcoma, caused by the reactivation of human herpesvirus type 8, and Merkel cell carcinoma of the skin, associated with Merkel cell polyomavirus. [5][6][7][8][9] Of the cancers presenting in organ transplant recipients that have no established infectious etiology, skin cancer is the most frequent form (95%), including squamous and basal cell carcinomas. [10][11][12][13] The incidence of skin cancer, the most common cancer in fair-skinned populations, is at least 50-fold higher in organ transplant recipients. 14-16 Large numbers of skin tumors (often more than 10) tend to develop over time in these at-risk subjects, thus

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“…Novel beta HPV PsV types were designed according to HPV prevalence in NMSC of both immune-suppressed and immune—competent patients, and to provide at least one type representative of different beta HPV species [73]. In general, novel beta HPV PsV showed variable infectivity and not all were useful in vivo .…”

Section: Discussionmentioning

confidence: 99%

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

et al. 2017

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Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

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Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland

Abstract: A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.

Cited by 32 publications

References 31 publications

Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis

Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

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