Betapapillomavirus infections : natural history and disease association

This thesis starts with a general introduction and a description of the development of a detection and genotyping method for Betapapillomavirus types. This genotyping method is used in three chapters to acquire more knowledge on the natural history of Betapapillomavirus infection. Very little is known about this subject and more knowledge could support future studies into the clinical relevance of these viruses. Furthermore, three subsequent chapters focus on possible associations of betaPV infection with three different (pre)malignant diseases. A final chapter includes general discussion and conclusions.Research described in this thesis was supported by DDL Diagnostic Laboratory, by the Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, by EC grant QLK-CT-00201179, by Labo Bio-medical Products B.V., and by Stichting Pathologie Onderzoek en Ontwikkeling. Publication of this thesis has been supported by the Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center.UBL - phd migration 201

Evaluation of a Novel Multiplex Human Papillomavirus (HPV) Genotyping Assay for HPV Types in Skin Warts

Public Health and primary careMinor Ailment

HPV type-specific distribution among family members and linen in households of cutaneous wart patients

Background Common and plantar warts are caused by human papillomaviruses (HPV). Mode of transmission of wart HPVs within families is largely unknown. Objective To demonstrate similarity of HPV type(s) among wart cases, family members and household linen. Methods In a cross-sectional study, swabs taken from 123 warts and foreheads of 62 index patients and 157 family members and from 58 kitchen towels and 59 bathroom mats were tested for DNA of 23 cutaneous wart-associated HPV types. Generalized estimating equations (GEE) were used to estimate the chance of detecting the same HPV type as was found in the index patients on the family contacts and on the kitchen towels and bathroom mats. Results HPV1, HPV2, HPV27 and HPV57 were the most prevalent types in the warts of the index patients. Altogether, 60 (42.3%) of the 142 family members without warts had HPV DNA on their foreheads. When HPV1 and HPV2 were found in the warts, these types were also frequently (>50%) found on the foreheads of index patients and their family members, as well as on the kitchen towels and the bathroom mats. HPV27 and HPV57 were less frequently found (<25%) on foreheads and linen. No associations were found for age, sex and site of HPV DNA presence. Conclusion Dissemination of skin wart-causing HPV types, from wart cases to household contacts and linen, such as kitchen towels and bathroom mats, is more likely for HPV1 and HPV2 than for HPV27 and HPV57. The role of towels and bathroom mats in HPV transmission deserves further investigation.Dermatology-oncolog

No effect of topical digoxin and furosemide gel for patients with external anogenital warts

Drug Delivery Technolog

Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions

AIMS\nMETHODS\nRESULTS\nCONCLUSION\n To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL).\nTwo randomized controlled trials in patients with external AGW and vulvar HSIL were conducted. Patients received topical omiganan 2.5% or placebo gel once daily for 12 weeks with a follow-up of 12 weeks. Safety and tolerability were monitored and pharmacodynamics and clinical efficacy of omiganan were assessed by analysing lesion count, size and viral load. Self-reported pain, itch and quality of life were assessed by an electronic diary and questionnaire.\nTwenty-four AGW and 12 vulvar HSIL patients were enrolled. All patients had a high treatment adherence (99%). No serious adverse events occurred and all adverse events (n = 27) were mild, transient and self-limiting. The treatment groups were not different in terms of safety and tolerability, lesion count and size, and patient-reported outcomes pain, itch and quality of life. Human papillomavirus load significantly reduced after 12 weeks of treatment with omiganan compared to placebo (-96.6%; 95% confidence interval -99.9 to -7.4%; P = .045) in AGW patients only.\nTopical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced human papillomavirus load after 12 weeks of treatment in AGW patients.Drug Delivery Technolog

Evaluation of a Novel Broad-Spectrum PCR-Multiplex Genotyping Assay for Identification of Cutaneous Wart-Associated Human Papillomavirus Types

A large number of human papillomavirus (HPV) types, distributed over five papillomavirus genera, are detectable in the skin. HPV types belonging to the alpha, gamma, and mu genera have been detected in cutaneous warts. A state-of-the-art HPV genotyping assay for these cutaneous wart-associated HPV types does not exist although warts constitute a highly prevalent skin condition, especially in children (33%) and organ transplant recipients (45%). Cutaneous warts are again the focus of attention as their clinical relevance rises with the increasing number of chronically immunosuppressed patients. The objective of this study was to develop and evaluate a DNA-based genotyping system for all known cutaneous wart-related HPV types using PCR and Luminex xMAP technology. The broad-spectrum PCR amplified DNA of all known wart-associated HPV types from the genera alpha (HPVs 2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91, and 94), gamma (HPVs 4, 65, 95, 48, 50, 60, and 88), mu (HPVs 1 and 63), and nu (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterized cutaneous wart biopsy specimens showing high specificity. HPV was also identified in 96% of 100 swabs from nongenital cutaneous warts. HPV types 1, 2, 27, and 57 were the most prevalent HPV types detected in 89% of the swabs. In conclusion, this Luminex-based genotyping system identifies all known cutaneous wart HPV types including phylogenetically related types, is highly HPV type specific, and is suitable for large-scale epidemiological studies.Minor Ailment

Transmission of betapapillomaviruses between domestic partners in an Australian community

Background: Betapapillomaviruses may be associated with the development of cutaneous squamous cell carcinoma but little is known about their transmission. One suggestion is that they are transmitted through close skin contact. Objectives: To test this hypothesis we assessed whether co-habiting opposite-sex couples were more or less likely to share betaPV types than each member of the couple and an age-matched, opposite-sex control. Study design: Betapapillomavirus was measured in eyebrow hairs of 57 couples and 114 age- and sex-matched controls. We compared the proportion of partners who shared at least one betaPV type with the proportion of control partnerships sharing a betaPV type. We further subdivided those who shared at least one type into those who shared only one and those who shared more than one. We tested the significance of differences in these proportions using Chi-squared tests. A case-wise concordance index was used to calculate the overall concordance of the partners and the control pairings. Results: At least one betaPV type was shared by 39% of the co-habiting couples and 26% of the control pairs (p = 0.10). When restricted to all people with at least one virus infection (26 couples)74% of the partners and 46% of the control pairs shared at least one type (p = 0.02). The case-wise concordance index for partners was 0.28 (95% CI 0.21-0.35) and for the matched control pairs 0.16 (95% CI 0.12-0.20) (p < 0.001). Conclusions: Our results support the hypothesis that skin-to-skin contact is the primary means of beta-papillomavirus transmission. (C) 2009 Elsevier B.V. All rights reserved.Dermatology-oncolog

Effect of Quadrivalent Human Papillomavirus Vaccination on Oral Squamous Cell Papillomas

Dermatology-oncolog

Nasal microbiota dominated by Moraxella spp. is associated with respiratory health in the elderly population: a case control study

BackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal microbiota profiles are associated with age and RTIs.MethodsNasal and oropharyngeal swabs of 152 controls and 152 patients with an RTI were included. The latter group consisted of 72 patients with an upper respiratory tract infection (URTI) and 80 with a lower respiratory tract infection (LRTI). Both nasal and oropharyngeal swabs were subjected to microbiota profiling using amplicon sequencing of the 16S rRNA gene. Moraxella species were determined using quantitative real-time PCR and culture.ResultsBased on the microbiota profiles of the controls and the patients with an RTI, eight nasal and nine oropharyngeal microbiota clusters were defined. Nasal microbiota dominated by either Moraxella catarrhalis or Moraxella nonliquefaciens was significantly more prevalent in elderly compared to mid-aged adults in the control group (p=0.002). Dominance by M. catarrhalis/nonliquefaciens was significantly less prevalent in elderly with an LRTI (p=0.001) compared to controls with similar age.ConclusionsNasal microbiota dominated by M. catarrhalis/nonliquefaciens is associated with respiratory health in the elderly population.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

High prevalence of cutaneous warts in elementary school children and the ubiquitous presence of wart-associated human papillomavirus on clinically normal skin

Dermatology-oncolog