Betapapillomaviruses in the anal canal of HIV positive and HIV negative men who have sex with men

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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“…Of note, although previously considered strictly cutaneous types, beta HPV have been found to frequently infect anal and oral mucosa [71, 72]. …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Recently, the prevalence of anal β-HPV infection and type distribution was analyzed among Slovenian MSM of which 17% were HIV positive and β-HPV was detected in 65.2% of specimens [9]. To our knowledge this is the first report to describe the distribution of cutaneous HPVs in the anal canal of men from three countries, most of whom are MSW, and to investigate risk factors associated with β-HPV detection.…”

Section: Discussionmentioning

confidence: 99%

Diversity of human papillomavirus in the anal canal of men: the HIM Study

Sichero

Nyitray²,

Nunes

et al. 2015

Clinical Microbiology and Infection

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Human papillomavirus (HPV) infections are associated with development of anogenital lesions in men. There are no reports describing the distribution of non-alpha HPV types in the anal canal of a sexually diverse men group. The HIM (HPV in Men) Study is a multicenter study of the natural history of HPV infection in Brazil, Mexico and USA. At baseline, 12% of anal canal specimens PCR HPV-positive were not typed by the Roche Linear Array and were considered unclassified. Our goal was characterizing HPVs among these unclassified specimens at baseline and assess associations with participant socio-demographic and behavioral characteristics. Unclassified HPVs were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. Further analysis was conducted using FAP primers. Of men with unclassified HPV at the anal canal, most (89.1%) were men who have sex with women (MSW). Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. A total of 18, 26, and 3 different α-, β- and γ-HPV types were detected, respectively. Compared to older men (45-70 years), α-HPVs were more commonly detected among young men (18-30 years) whereas β-HPVs were more frequent among mid-adult men (31-44 years). β-HPVs were more common among heterosexual men (85.0%) than non-heterosexual men. β2-HPV types composed all β-HPVs detected among non-heterosexual men. The high prevalence of β-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse.

show abstract

“…Recently, the prevalence of anal β-HPV infection and the type distribution were analysed among Slovenian MSM, of whom 17% were HIV-positive, and β-HPV was detected in 65.2% of specimens [9]. To our knowledge, this is the first report to describe the distribution of cutaneous HPVs in the anal canal of men from three countries, most of whom are MSW, and to investigate the risk factors associated with β-HPV detection.…”

Section: Discussionmentioning

confidence: 94%

“…HPV-150 was the only type not detected in any of the samples tested. Multiple β-HPV types were more likely to be detected at the genital (ranged from 2-19 types detected) than at the anal canal (2)(3)(4)(5)(6)(7)(8)(9) or oral cavity (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) (Table 1). …”

Section: Resultsmentioning

confidence: 99%

“…The β-HPV and γ-HPV genera have more genotypes than the α-HPV genus, and partial DNA sequence information points to the existence of hundreds of putative novel HPV types of both viral genera [5,6]. Recent data indicate a high prevalence of cutaneous HPV at diverse anatomical sites that are different from those from which they were isolated [7][8][9][10][11].…”

Section: Conclusõesmentioning

confidence: 99%

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Prevalência e diversidade de beta-papilomavírus em amostras anogenitais e orais de homens do estudo HIM

Nunes¹

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Betapapillomaviruses in the anal canal of HIV positive and HIV negative men who have sex with men

Cited by 19 publications

References 22 publications

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

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

Diversity of human papillomavirus in the anal canal of men: the HIM Study

Prevalência e diversidade de beta-papilomavírus em amostras anogenitais e orais de homens do estudo HIM

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