BACKGROUND: Cryotherapy is effective for common warts, but for plantar warts available treatments often fail. OBJECTIVES: Within a pragmatic randomised controlled trial, we examined whether... Show moreBACKGROUND: Cryotherapy is effective for common warts, but for plantar warts available treatments often fail. OBJECTIVES: Within a pragmatic randomised controlled trial, we examined whether subgroups of common and plantar warts have a favourable natural course or response to treatment based on wart-associated HPV type. STUDY DESIGN: Consecutive patients with new common or plantar warts were recruited in 30 Dutch family practices. Patients (n=250) were randomly allocated to liquid-nitrogen cryotherapy, 40% salicylic acid self-application, or wait-and-see policy. Before treatment, swabs were taken from all separate warts and analysed by a broad spectrum HPV genotyping assay. At 13 weeks, cure rates with 95% confidence intervals of common and plantar warts on intention to treat basis were compared between treatment arms for the different wart-associated HPV types. RESULTS: In total, 7% of swabs tested negative for HPV DNA and 16% contained multiple types, leaving 278 of 371 common swabs (75%) and 299 of 373 plantar swabs (80%) with a single type for analysis. After wait-and-see policy, cure rates were 2/70 (3%, 95% confidence interval 1-10) for HPV 2/27/57-associated common warts, 4/58 (7%, 3-16) for HPV 2/27/57-associated plantar warts, and 21/36 (58%, 42-73) for HPV 1-associated plantar warts. After cryotherapy, cure rates were 30/44 (68%, 53-80), 6/56 (11%, 5-21), and 15/23 (65%, 45-81); after salicylic acid 16/87 (18%, 12-28), 15/60 (25%, 16-37), and 24/26 (92%, 76-98), respectively. CONCLUSIONS: HPV type influenced the natural course and response to treatment for plantar warts. HPV testing potentially optimises wart treatment in primary care. Show less
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... Show moreWe 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 Show less
Koning, M.N.C. de; Polderman, M.C.A.; Waterboer, T.; Schegget, J. ter; Feltkamp, M.C.W.; Pawlita, M.; ... ; Quint, W.G.V. 2011
P>Background Recent studies revealed that Betapapillomavirus (betaPV) infections are highly prevalent. Skin diseases such as psoriasis, characterized by keratinocyte hyperproliferation, and... Show moreP>Background Recent studies revealed that Betapapillomavirus (betaPV) infections are highly prevalent. Skin diseases such as psoriasis, characterized by keratinocyte hyperproliferation, and atopic dermatitis (AD), dominated by cutaneous inflammation, might have an impact on viral life cycle and immune response induction. Objectives To investigate whether betaPV infection is different in psoriasis and AD. Methods Twenty-seven patients with psoriasis and 17 with AD were included for betaPV genotyping using eyebrow hairs, and for seroresponse determination. Results BetaPV DNA was found significantly more often in patients with psoriasis than in those with AD (100% vs. 81%, P = 0 center dot 022) and the mean number of betaPV types was higher (4 center dot 8 vs. 2 center dot 1 types, P = 0 center dot 002). In contrast, the seroprevalence in patients with AD was significantly higher compared with that in patients with psoriasis (88% vs. 56%, P = 0 center dot 023). Type-specific concordance of serological response to the betaPV type detected in eyebrow hairs was 27% in patients with psoriasis and 47% in those with AD (P = 0 center dot 019). Conclusions We speculate that the condition of the skin and the immunological state of the patients have an important impact on the life cycle of betaPV. Show less
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... Show moreHuman 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. Cancer Res; 70(23); 9777-86. (C)2010 AACR. Show less
Betapapillomaviruses (beta PVs) 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... Show moreBetapapillomaviruses (beta PVs) 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 beta PV types that are independently related to skin carcinogenesis, they are unlikely to be identified using standard epidemiological methods. Show less
Betapapillomavirus (mu PV) DNA and seroresponses are highly prevalent in the general population and both are frequently used as infection markers in epidemiological studies to elucidate an... Show moreBetapapillomavirus (mu PV) 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 beta PV 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 beta PV DNA in eyebrow hairs and L1 antibodies of the same beta PV type co-occurred more frequently than would be expected by chance in both a cross-sectional assessment and a longitudinal study. beta PV 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 beta PV DNA and antibodies was compared with expected values based on prevalence. A case-wise concordance index was used to calculate the overall concordance of beta PV DNA and antibodies of the same type. No significant associations were found between the presence or persistence of beta PV 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 beta PV antibody responses in adults are not primarily driven by beta PV infection as measured in eyebrow hairs. Other factors, such as viral load, may play a more pivotal role in the induction of detectable seroresponses. Show less
Human papillomaviruses from the genus beta (betaPV) are a possible cause of cutaneous squamous cell carcinoma (SCC). We compared the betaPV infections in SCC and in sets of cutaneous tissues... Show moreHuman papillomaviruses from the genus beta (betaPV) are a possible cause of cutaneous squamous cell carcinoma (SCC). We compared the betaPV infections in SCC and in sets of cutaneous tissues collected from a series of individual SCC patients to determine concordance and to assess the adequacy of eyebrow hairs as noninvasive markers of betaPV infection. Biopsies of SCC tumors, perilesional tissue, normal skin from the mirror image of nonfacial SCC and plucked eyebrow hairs were collected from 21 patients with incident SCC living in Queensland, Australia. These were tested for the presence of DNA from 25 different betaPV types. Overall prevalence of betaPV was high in every sample type, ranging from 81% to 95%. The median number of types was significantly higher in the SCC tumour (6), perilesional skin (5) and eyebrow hairs (5) than in normal skin (2). Comparing SCC tissue with other sample types within patients showed 63 overlapping infections with eyebrow hairs (71%; 95% CI: 60-80); 56 with perilesional skin samples (63%; 95% CI: 52-73) and 23 with normal skin samples (26%; 95% CI: 17-36). The sensitivity of eyebrow hair testing for detection of betaPV in the tumor was 82% (95% CI: 57-96) with concordance defined as 50% of betaPV types in common and 29% (95% CI: 10-56) for 100% concordance. These findings support the concept that perilesional skin represents an area of field change involving betaPV preceding SCC development and indicate that eyebrow hairs can serve to some degree as an easily collected marker of tumor betaPV status in epidemiological studies. Show less
Koning, M.N.C. de; Schegget, J. ter; Eekhof, J.A.H.; Kamp, M.; Kleter, B.; Gussekloo, J.; ... ; Quint, W.G.V. 2010
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... Show moreA 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. Show less
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... Show moreBackground: 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. Show less
Koning, M.N.C. de; Schegget, J. ter; Eekhof, J.A.H.; Kamp, M.; Kleter, B.; Gussekloo, J.; ... ; Quint, W.G.V. 2010
A large number of HPV types, distributed over five papillomavirus genera, is detectable in the skin. HPV types belonging to the alpha, gamma and mu genus have been detected in cutaneous warts. A... Show moreA large number of HPV types, distributed over five papillomavirus genera, is detectable in the skin. HPV types belonging to the alpha, gamma and mu genus 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 alpha- (HPV2, 3, 7, 10, 27, 28, 29, 40, 43, 57, 77, 91 and 94), gamma- (4, 65, 95, 48, 50, 60 and 88), mu- (HPV1 and 63) and nu-genus (HPV41). The probes were evaluated using plasmid HPV DNA and a panel of 45 previously characterised cutaneous wart biopsies showing high specificity. HPV has also been identified in 96% of 100 swabs from non-genital 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. Show less
