Project description:Genetic variation of 49 human papillomavirus (HPV) 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP) (n = 17), genital warts (n = 43), anal cancer (n = 6) and cervical neoplasia cells (n = 5), was determined by sequencing the long control region (LCR) and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65%) clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04). This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02). Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these HPV types.
Project description:ObjectivesTo estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers.MethodsPaired oral rinse samples and anogenital samples were available from 151 HIV-negative MSM within a larger cross-sectional survey. All samples were tested in parallel for 21 types of HPV DNA using an in-house assay.ResultsThe median age of participants was 30 (IQR 25-35). The prevalence of any oral HPV and of high-risk HPV (HR-HPV) was 13.7% (n=21; 95% CI 8.7 to 20.2) and 5.9% (n=9; 95% CI 2.7 to 10.9) compared with 64.9% (n=98; 95% CI 56.7 to 72.5) and 34.4% (n=52; 95% CI 26.9 to 42.6) in any anogenital sample, respectively. The prevalence of types prevented by the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines was 1.3% (95% CI 0.2 to 4.7), 2.6% (95% CI 0.7 to 6.6) and 4.6% (95% CI 1.9 to 9.3), respectively. There was no concordance between HPV genotypes detected in oral and anogenital sites.ConclusionsHR-HPV DNA, including HPV 16/18, was detected in oral specimens from HIV-negative MSM attending sexual health clinics, suggesting a potential role for vaccination, but is far less common than anogenital infection. How this relates to the risk and natural history of HPV-related head and neck cancers warrants further study. Lack of concordance with anogenital infection also suggests that oral HPV infection should be considered separately when estimating potential vaccine impact.
Project description:The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325.
Project description:Papillomavirus (PV) is a well-known pathogen associated with epithelial and mucosal neoplastic diseases. In contrast to human PVs, characterization of animal PVs from the aspect of anogenital neoplasm is still on a learning curve. In the present study, two vulval and one anal warts, histologically diagnosed as fibropapillomas, excised from dairy cattle were analyzed. PCR and sequencing revealed that bovine papillomavirus type 1 (BPV-1) and BPV-2 were detected from anal and vulval fibropapillomas, respectively. Immunohistochemistry detected PV antigen in a few differentiated keratinocytes of one vulval case. Reverse-transcriptase PCR detected the early region, but not the late region of BPV mRNA in all three cases. The present study will provide new insight into the relationship between BPV and anogenital papilloma in cattle.
Project description:To investigate the composition of human papillomavirus (HPV) types in anogenital warts (AGWs), viral nucleic acid in 110 AGWs, pooled into 11 specimen pools, were subjected to viral metagenomic analysis. After finding HPV7 in AGWs, conventional PCR screening was performed for HPV7 in other 190 individual AGW specimens. Viral metagenomic results indicated that 29 different types of HPV were recovered, with HPV11 and HPV6 showing the highest proportion of sequence reads. HPV7 was detected in 7 of 11 pools, 5 of which contained abundant HPV7 sequence reads. 24 complete genomes of HPV were acquired in viral metagenomic analysis, including 5 HPV7 genomes, based on which phylogenetic analysis and pairwise sequence comparison were conducted. PCR screening for HPV7 in other 190 individual AGW specimens revealed 25 positive cases (13.16%), of which the amplified fragments were sequenced and confirmed to be HPV7 sequences. Although HPV7 was generally found in hand warts and recently also in warts in toe webs, our data suggested that the role of HPV7 in AGW should be considered in the future clinical test and vaccine development for AGWs.
Project description:BackgroundDespite the strong evidence of HPV infection as the etiological agent in a subset of oral cancer, oral α-HPV detection is rare in healthy individuals, and little is known of the existing of novel HPV types in oral cavity.ObjectiveWe determined whether novel HPV types can be isolated from oral rinse samples collected from healthy individuals.Study designWe performed rolling circle amplification (RCA) coupled with degenerated PCR assay on 48 oral rinse samples to amplify novel HPV types. Full length HPV DNA was cloned using long range PCR. Quantitative type specific Taqman assays were used to determine the prevalence of novel HPV types in 158 archived oral tissue samples.ResultsWe were able to isolate four novel human papillomavirus types. Full length HPV DNA was cloned for three of the four novel HPV types. All four HPV types belong to the genus Gammapapillomavirus (γ-PV), where HPV 171 is most closely related to HPV 169, showing 88% similarity; HPV 172 is most closely related to HPV 156, showing 70% similarity; HPV 173 is most closely related to HPV 4, showing 73% similarity; oral sample lavage (OSL) 37 is most closely related to HPV 144, showing 69% similarity. Finally, we showed that HPV 173 was rarely present in oral tissues (2/158), HPV 172 was only detected in normal oral tissues (25/76), and HPV 171 was more prevalent in malignant oral tissues (17/82 vs. 10/76, p=0.21).ConclusionsNovel γ-HPV types are present in oral cavity of healthy individuals.
Project description:The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: K14E6/E7 transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with Mus musculus papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (K14E6/E7) or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia. Mice were treated with or without topical DHA at the cervix or anus and with or without topical treatment with the chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) at the anus of in transgenic mice to induce neoplastic progression. Mice were monitored for overt tumor growth, and tissue was harvested after 20 weeks of treatment and scored for severity of histological disease. For MmuPV1-infected mice, anogenital lavages were taken to monitor for viral clearance. Tissues were also evaluated for viral gene expression at the RNA and/or protein levels. Treatment with topical DHA did not reduce dysplasia in the anogenital tract in either papillomavirus-induced mouse model and did not prevent progression to anal cancer in the DMBA-treated K14E6/E7 mice.
Project description:IntroductionHPV infection is a common risk factor for all anogenital cancers. However, there are important differences in the epidemiology of anogenital cancers and these have not been compared considering diverse epidemiological indicators over a long period of time. To fill this gap, we investigated incidence, mortality, and survival trends of anogenital cancers over a period of three decades.MethodsWe conducted an observational registry-based study using data from the population-based cancer registry of Granada in southern Spain. We collected data on all incident cases of anogenital cancer (cervical, anal, penile, vulvar, and vaginal cancer) diagnosed between 1985 and 2017. We calculated crude and age-standardized incidence and mortality rates, and 1, 3, and 5-year overall and net survival. We further conducted time-trend analysis calculating annual percent changes (APC) for each cancer site.ResultsThe incidence of anogenital cancers decreased slightly during the past 30 years, with the exception of vulvar cancer, where a slight increase was observed. Mortality decreased significantly for cervical cancer over the study period but increased non-significantly for the remaining cancer sites. Survival rates were similar to those reported in comparable countries and increased for cervical and vulvar cancer.DiscussionCervical cancer was the greatest contributor to the burden of anogenital cancers and showed a marked improvement in all indicators in comparison to the remaining cancer sites.