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  • 1
  • 2
    Keywords: CANCER ; tumor ; BLOOD ; carcinoma ; CELL ; human ; DIAGNOSIS ; COHORT ; EPIDEMIOLOGY ; RISK ; TIME ; INFECTION ; ANTIGEN ; antibodies ; antibody ; virus ; NO ; DIFFERENCE ; PLASMA ; COMPONENT ; VIRUS-LIKE PARTICLES ; HPV ; case-control studies ; squamous cell carcinoma ; INDIVIDUALS ; L1 ; INFECTIONS ; PREVALENCE ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; SKIN-CANCER ; glutathione-S-transferase ; CELL CARCINOMA ; ONCOLOGY ; case control study ; case-control study ; PATTERN ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; prospective studies ; case control studies ; ACTINIC KERATOSES ; USA ; prospective ; prospective study ; UNIT ; SQUAMOUS-CELL ; serology ; HUMAN PAPILLOMAVIRUSES ; SEROPREVALENCE ; case control ; cutaneous squamous cell carcinoma (SCC) ; HPV types ; human papillomavirus (HPV) ; ORGAN-TRANSPLANTATION ; prospective case-control
    Abstract: In a prospective pilot study nested in the EPIC-Oxford cohort, we examined the seroprevalence of antibodies against the L1 antigen of 38 human papilloma virus (HPV) types among 39 cases of cutaneous squamous cell carcinoma (SCC) for whom plasma was collected prior to diagnosis (incident) and 80 controls. Fifteen cases having already developed SCC at blood collection (prevalent) were also tested. There were no statistically significant differences in the seroprevalence of antibodies against any of the HPV types examined between incident cases and controls, nor was there a difference in the seroprevalence of multiple infections. However, consistent with results from published case-control studies, the seroprevalence of many beta-HPV types was higher among prevalent cases than among either incident cases or controls. For example the seroprevalence of antibodies against HPV-8 was 20% (16/80) in controls, 23% (9/39) among incident cases and 40% (6115) among prevalent cases. Among the incident cases only, the seroprevalence was 16% (5/32) among those for whom blood was collected 18+ months prior to diagnosis, but 57% (4/7) among those for whom diagnosis was within 18 months of blood collection, a pattern seen for many of the HPV types. This might suggest that if HPV is involved in the aetiology of SCC, the process occurs close to the time of diagnosis, or that the antibody response observed in people with SCC is a consequence of tumor formation. Further and larger prospective studies are needed to clarify the role of HPV in the aetiology of cutaneous SCC. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17565742
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  • 3
    Keywords: Germany ; human ; DISEASE ; DISEASES ; HISTORY ; POPULATION ; DISTINCT ; PROTEIN ; TIME ; INFECTION ; SKIN ; papillomavirus ; ALPHA ; antibodies ; antibody ; PATTERNS ; AGE ; WOMEN ; MEN ; CAPSID PROTEIN ; human papillomavirus ; VIRUS-LIKE PARTICLES ; HIGH-RISK ; HPV ; BETA ; HUMAN-PAPILLOMAVIRUS ; Jun ; SQUAMOUS-CELL CARCINOMA ; POLYMERASE-CHAIN-REACTION ; L1 ; CHILDREN ; NATURAL-HISTORY ; PREVALENCE ; NONMELANOMA SKIN CANCERS ; glutathione-S-transferase ; SERUM ; ADULT ; ADULTS ; SAN-FRANCISCO ; review ; RE ; PATTERN ; papillomaviruses ; GAMMA ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; HPV 16 ; USA ; YOUNG-ADULTS ; INFECTIOUS-DISEASES ; microbiology ; serology ; multiplex serology ; SEROPREVALENCE ; GENERAL-POPULATION ; HPV types ; MAJOR CAPSID PROTEIN ; HPV-16 ; CUTANEOUS HUMAN PAPILLOMAVIRUSES ; FOOD-CONSUMPTION HABITS ; NORMAL CERVICAL SMEARS
    Abstract: The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age-and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life
    Type of Publication: Journal article published
    PubMed ID: 18566657
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  • 4
    Keywords: CELLS ; tumor ; CELL ; human ; COMMON ; DISEASE ; SITES ; PROTEINS ; SAMPLE ; SAMPLES ; TUMORS ; TIME ; PATIENT ; DNA ; SKIN ; papillomavirus ; antibody ; IN-SITU ; LESIONS ; COPY NUMBER ; human papillomavirus ; GENOTYPES ; HPV ; REPLICATION ; glutathione-S-transferase ; PSORIASIS ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; hair ; GENOTYPE ; NONMELANOMA SKIN-CANCER ; USA ; PLUCKED EYEBROW HAIRS ; CLINICAL-ASPECTS ; HAIRS ; HUMAN-PAPILLOMAVIRUS-DNA
    Abstract: Epidermodysplasia verruciformis (EV) is a rare disease, characterized by cutaneous warts and associated with a strong predisposition to beta-genus human papillomavirus (HPV). Earlier studies reported high copy numbers of HPV-DNA in nearly all skin tumors from EV patients, but neither HPV replication status in non-lesional skin nor anti-HPV seroreactivity in these patients have been reported yet. We therefore performed a comprehensive viral load analysis for the more common beta-HPV types on skin samples and plucked eyebrow hairs from four EV patients treated at our dermatology department. The results clearly demonstrate that they carry a multiplicity (up to eighteen types) of beta-HPV genotypes in both skin sites. Worthy of note, a high intrapatient concordance for specific types between hair bulbs and skin biopsies was observed and the same beta-PV profile was maintained over time. Viral load analysis revealed a load range between less than one HPV-DNA copy per 100 cells to more than 400 HPV-DNA copies per cell in both eyebrow hairs and skin proliferative lesions. Evaluation of seroreactivity to beta-HPV types in the four EV patients revealed that antibodies against the 16 beta-HPV were significantly more prevalent and showed higher titers than in the controls
    Type of Publication: Journal article published
    PubMed ID: 18923444
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  • 5
    Keywords: SPECTRA ; CANCER ; carcinoma ; CELL ; Germany ; human ; EXPOSURE ; HISTORY ; POPULATION ; RISK ; GENOME ; radiation ; RESPONSES ; DNA ; INFECTION ; CARCINOGENESIS ; SKIN ; papillomavirus ; antibodies ; antibody ; LESIONS ; WOMEN ; MEN ; RISK FACTOR ; human papillomavirus ; HPV ; HUMAN-PAPILLOMAVIRUS ; SQUAMOUS-CELL CARCINOMA ; NETHERLANDS ; squamous cell carcinoma ; INDIVIDUALS ; sensitivity ; NATURAL-HISTORY ; RENAL-TRANSPLANT RECIPIENTS ; glutathione-S-transferase ; SERUM ; CELL CARCINOMA ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; development ; RISK-FACTOR ; SQUAMOUS-CELL ; SUN EXPOSURE ; virology ; SEROPREVALENCE ; biotechnology ; CUTANEOUS HUMAN PAPILLOMAVIRUSES ; CONFIDENCE ; SCC ; PAPILLOMAVIRUS TYPES
    Abstract: Solar UV radiation is the main risk factor for cutaneous squamous cell carcinoma (SCC), but infections with skin human papillomavirus (HPV) types have also been linked to the development of SCC. Little is known about the natural history of these infections and whether the seroprevalence of skin HPV types is affected by ambient or individual levels of sun exposure. This study investigated this by analysing sera for antibodies to 26 skin HPV types from five phylogenetic genera obtained from 807 healthy individuals from the Netherlands, Italy and Australia, countries with strong differences in sunlight intensity. Overall HPV seroprevalence, was similar across the three countries (50-57% for beta-HPV types, 40-48% for gamma-HPV types), and the most frequent beta-HPV and gamma-HPV types were the same in all countries. The highest seroprevalences; for 24 of the 26 skin HPV types were observed in Italy (114 types) and Australia (ten types). Seroprevalence among men was generally higher than among women, and the male sex was significantly associated with both beta-HPV [odds ratio (OR) 2.81, 95 % confidence interval (CI) 1.64-4.821 and gamma-HPV (OR 2.42, 95% CI 1.40-4.18) antibodies in Australia. The only measure of sun sensitivity or UV exposure significantly associated with skin HPV seroprevalence was found for weekend sun exposure in Australia and beta-HPV antibodies. It was concluded that type spectra and HPV seroprevalence are similar in countries with different sunlight intensity, and that levels of UV exposure do not play a strong role in the development of skin HPV antibodies in this study population
    Type of Publication: Journal article published
    PubMed ID: 19386782
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  • 6
    Keywords: CANCER ; Germany ; human ; CLASSIFICATION ; QUANTIFICATION ; DISEASE ; DISEASES ; PROTEIN ; PROTEINS ; COMPLEX ; RESPONSES ; COMPLEXES ; INFECTION ; RISK-FACTORS ; ANTIGEN ; FLOW ; papillomavirus ; ASSOCIATION ; antibodies ; antibody ; virus ; IN-SITU ; ASSAY ; GLUTATHIONE ; NUMBER ; REPRODUCIBILITY ; CERVICAL-CANCER ; FUSION ; FUSION PROTEINS ; human papillomavirus ; HPV ; E6 ; case-control studies ; LINKED-IMMUNOSORBENT-ASSAY ; glutathione-S-transferase ; FUSION PROTEIN ; E6 ONCOPROTEIN ; SERUM ; CHEMISTRY ; ELISA ; case-control study ; PROGRAM ; RE ; case control studies ; multiplex ; MICROSPHERE IMMUNOASSAY
    Abstract: Background: More than 100 different human papillo-maviruses (HPVs) can cause proliferative diseases, many of which are malignant, such as cervical cancer. HPV serology is complex because infection and disease lead to distinct type-specific antibody responses. Using bead-based technology, we have developed an assay platform that allows the simultaneous detection of antibodies against up to 100 in situ affinity-purified recombinant HPV proteins. Methods: Twenty-seven HPV proteins were expressed as glutathione S-transferase fusion proteins and affinity-purified in one step by incubation of glutathione-displaying beads in bacterial lysate. Spectrally distinct bead sets, each carrying one particular antigen, were mixed, incubated with serum, and differentiated in a flow cytometer-like analyzer (xMAP; Luminex Corp). Antibodies bound to the antigens were detected via fluorescent secondary reagents. We studied 756 sera from 2 case-control studies of cervical cancer. Results: Glutathione S-transferase fusion proteins bound with high affinity to glutathione-displaying beads (K-d = 6.9 X 10(-9) mol/L). The dynamic range of multiplex serology covered 1.5 orders of magnitude, and antibodies were detected at serum dilutions 〉 1:1 000 000. Imprecision (median CV) was 〈= 5.4%, and assay reproducibility was high (R-2 = 0.97). Results on clinical samples showed high concordance with ELISA (kappa = 0.846), but multiplex serology exhibited increased detection of weak antibody responses. Antibodies to the E6 oncoproteins of the rare HPV types 52 and 58 were associated with cervical cancer (P 〈 0.001). Conclusion: Multiplex serology enables antibody analyses of large numbers of sera against up to 100 antigens in parallel and has the potential to replace ELISA technology. (c) 2005 American Association for Clinical Chemistry
    Type of Publication: Journal article published
    PubMed ID: 16099939
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  • 7
    Keywords: CANCER ; tumor ; carcinoma ; CELL ; COMBINATION ; human ; EPIDEMIOLOGY ; RISK ; TISSUE ; TUMORS ; validation ; PATIENT ; DNA ; INFECTION ; MARKER ; BIOMARKERS ; TISSUES ; SKIN ; papillomavirus ; antibodies ; antibody ; skin cancer ; MARKERS ; PCR ; human papillomavirus ; HPV ; HUMAN-PAPILLOMAVIRUS ; SQUAMOUS-CELL CARCINOMA ; squamous cell carcinoma ; NORMAL TISSUE ; SERIES ; sensitivity ; specificity ; NONMELANOMA SKIN CANCERS ; RENAL-TRANSPLANT RECIPIENTS ; BIOPSY ; SKIN-CANCER ; basal cell carcinoma ; glutathione-S-transferase ; SERUM ; CELL CARCINOMA ; ELISA ; ONCOLOGY ; EXTENSION ; ARRAY ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; HIGH PREVALENCE ; hair ; TUMOR TISSUE ; biomarker ; TECHNOLOGY ; ACTINIC KERATOSES ; NORMAL SKIN ; technique ; USA ; RISK-FACTOR ; CANCERS ; SQUAMOUS-CELL ; nonmelanoma skin cancer ; IMMUNOCOMPETENT INDIVIDUALS ; NOV ; validation studies ; BASAL-CELL ; MICROARRAY PRIMER EXTENSION ; MULTIPLEX PCR
    Abstract: Cutaneous human papillomavirus (HPV) may be associated with the development of nonmelanoma skin cancer (NMSC), as suggested by reports of HPV DNA in NMSC tumors. HPV has also been investigated as an NMSC risk factor in epidemiologic studies, although findings vary across studies that used different biomarkers of HPV infection in normal tissues. To identify appropriate biomarkers for use in future epidemiologic studies, we conducted a sampling validation study. NMSC tumor tissue was obtained from 20 patients with pathology-confirmed basal or squamous cell carcinoma of the skin, in addition to several normal tissues, including eyebrow hairs, normal skin swabs obtained using multiple techniques, normal skin punch and shave biopsies, and serum for antibody measurement. Presence of cutaneous HPV DNA in tissues was measured with multiplex PCR using HPV type-specific primers and array primer extension (APEX) for HPV typing. Antibody detection was based on glutathione-S-transferase capture ELISA in combination with fluorescent bead technology. Using HPV DNA in tumor tissues as a gold standard, sensitivity and specificity were calculated for each measure of HPV infection in normal tissues. beta-Papillomavirus DNA was observed in tumor tissues in 60% of patients. The normal skin punch biopsy demonstrated optimal sensitivity (75%) and specificity (75%). Biomarkers obtained using less-invasive techniques demonstrated poor specificity when considered individually, although specificity improved when biomarkers were combined. Based on the current case series, the combinations of antibodies + eyebrow hairs or antibodies + eyebrow hairs + Dacron swabs are the optimal, minimally invasive markers of cutaneous HPV infection for use in epidemiologic studies. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18729188
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  • 8
    Keywords: CANCER ; carcinoma ; CELL ; human ; COMMON ; COHORT ; EPIDEMIOLOGY ; HISTORY ; POPULATION ; RISK ; PROTEINS ; TIME ; DNA ; INFECTION ; RISK-FACTORS ; ANTIGEN ; SKIN ; papillomavirus ; ASSOCIATION ; SUSCEPTIBILITY ; antibodies ; antibody ; AGE ; WOMEN ; MEN ; RISK FACTOR ; human papillomavirus ; VIRUS-LIKE PARTICLES ; HPV ; HUMAN-PAPILLOMAVIRUS ; POPULATIONS ; case-control studies ; squamous cell carcinoma ; L1 ; PREVALENCE ; glutathione-S-transferase ; SERUM ; CELL CARCINOMA ; case control study ; case-control study ; RECIPIENTS ; HPV 16 ; TECHNOLOGY ; ACTINIC KERATOSES ; NONMELANOMA SKIN-CANCER ; HISTOLOGY ; USA ; UNIT ; RISK-FACTOR ; SQUAMOUS-CELL ; IMMUNOCOMPETENT INDIVIDUALS ; serology ; SEROPREVALENCE ; cutaneous squamous cell carcinoma (SCC) ; HPV types ; human papillomavirus (HPV) ; Genital warts ; CONFIDENCE ; organ transplant recipients ; SCC
    Abstract: A case-control study was conducted in 140 people with histology proven cutaneous squamous cell carcinoma (SCC) and 454 controls, nested within 2 cohorts of organ transplant recipients (OTR) recruited in London and Oxford between 2002 and 2006. All participants had a skin examination, completed a questionnaire and had serum tested for antibodies against the L1 antigen of 34 HPV types using Luminex technology. SCC was more common in men than women (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.1-2.8, p = 0.02) and in people with susceptibility to burn easily (OR = 3.0, 95%CI: 1.9-4.8; p 〈 0.001). The risk increased with increasing age (p-trend 〈 0.001), increasing time since transplant (p-trend 〈 0.001), increasing self-reported number of sunburns as a child (p(trend) 〈 0.001) and with the presence of viral warts (p 〈 0.001). As expected, antibodies against HPV 16 were associated with a self-reported history of an abnormal cervical smear among women (OR 5.1, 95%CI: 2.6-10.2) and antibodies against HPV 6 were associated with a self-reported history of genital warts (OR 4.0, 95%CI: 2.2-7.2). However, no clear associations between any of the HPV types examined (including cutaneous betaHPVs) and SCC were identified. For example, the seroprevalence of HPV 5 was 15% among cases and 9% among controls (p = 0.09) and the seroprevalence of HPV 8 was 23% among cases and 21% among controls (p = 0.6). Nor was seropositivity to multiple types associated with SCC. These serological data do not provide evidence for a role for HPV in the aetiology of cutaneous SCC among OTR in two UK-based populations. (C) 2009 UICC
    Type of Publication: Journal article published
    PubMed ID: 19588489
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  • 9
    Keywords: carcinoma ; CELL ; MODEL ; MODELS ; CARCINOGENESIS ; SKIN ; FREQUENCY ; antibodies ; antibody ; virus ; PATTERNS ; NUMBER ; HIGH-RISK ; BETA ; SQUAMOUS-CELL CARCINOMA ; NETHERLANDS ; INDIVIDUALS ; nutrition ; CELL CARCINOMA ; case-control study ; PATTERN ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; methods ; NONMELANOMA SKIN-CANCER ; SQUAMOUS-CELL ; HUMAN-PAPILLOMAVIRUS INFECTION ; viruses ; COINFECTION ; Type ; CONTRIBUTE ; Cutaneous
    Abstract: 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-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
    Type of Publication: Journal article published
    PubMed ID: 20392895
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  • 10
    Keywords: INFECTION ; antibodies ; CERVICAL-CANCER ; VIRUS-LIKE PARTICLES ; UNITED-STATES ; NATURAL-HISTORY ; PREVALENCE ; glutathione-S-transferase ; UNIVERSITY-STUDENTS ; SOUTH-KOREA
    Abstract: Background: To determine differences in the seroprevalence of high-risk human papillomavirus (hrHPV) types between men having sex with men (MSM), heterosexual men and women, we analyzed seroprevalence and risk factors for 8 hrHPV in the general population of Amsterdam, the Netherlands. Methods: We interviewed 1349 inhabitants aged 〉= 17 years and tested sera for antibodies against L1 capsid proteins of 8 hrHPV using Luminex-based multiplex serology. Risk factors for hrHPV were determined by multivariate Poisson analysis. Results: Seroprevalences for 8 hrHPV ranged from 13.1% for HPV-45 to 31.4% for HPV-35. Seropositivity for HPV-16 and HPV-18 was more common in women and MSM than in heterosexual men. HPV-16 and -18 were more common in subjects also having antibodies against other hrHPV types (prevalence rate ratio [PRR], 2.12, 95% confidence interval [CI] 1.52-2.97; and PRR, 2.00; 95% CI, 1.43-2.81, respectively) and/or herpes simplex virus type 2 (PRR, 1.69; 95% CI, 1.32-2.16; and PRR, 1.47; 95% CI, 1.13-1.92, respectively). HPV-18 was more common in persons with a history of sexually transmitted infections (STI) (PRR, 1.64; 95% CI, 1.20-2.25). HPV-35, -45, and -58 were more common in non-European ethnic groups. Conclusions: Prevalence of 8 hrHPV antibodies was high in the Amsterdam population, especially in MSM
    Type of Publication: Journal article published
    PubMed ID: 20729796
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