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
Background: It is currently unclear whether betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV... Show moreBackground: It is currently unclear whether betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Methods: Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the community-based Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age-and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. Results: SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR - 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Conclusions: Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. Impact: This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case-control studies. Cancer Epidemiol Biomarkers Prev; 20(6); 1171-7. (C)2011 AACR. 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
Objective To investigate the association between genus beta human papillomaviruses and the incidence of nonmelanocytic skin cancer in the general population. Design Population based case-control... Show moreObjective To investigate the association between genus beta human papillomaviruses and the incidence of nonmelanocytic skin cancer in the general population. Design Population based case-control study. Setting New Hampshire, USA. Participants 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus beta human papillomaviruses by multiplex serology. Main outcome measures Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to beta human papillomaviruses. Results Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual beta human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of beta types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous)=0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55). Conclusions These findings support a relation between genus beta human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression. Show less
