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  • 1
    Keywords: CANCER ; tumor ; carcinoma ; human ; CLASSIFICATION ; EXPOSURE ; RISK ; SITE ; PROTEIN ; PROTEINS ; TUMORS ; PATIENT ; DNA ; INFECTION ; FAMILY ; RISK-FACTORS ; SKIN ; MR ; papillomavirus ; ASSOCIATION ; antibodies ; IN-SITU ; risk factors ; PATHOGENESIS ; human papillomavirus ; VIRUS-LIKE PARTICLES ; HUMAN-PAPILLOMAVIRUS ; CARCINOMAS ; case-control studies ; squamous cell carcinoma ; INDIVIDUALS ; sensitivity ; RENAL-TRANSPLANT RECIPIENTS ; basal cell carcinoma ; glutathione-S-transferase ; CELL CARCINOMA ; case-control study ; population-based case-control study ; ASSOCIATIONS ; case control studies ; INTERVAL ; TECHNOLOGY ; RISK-FACTOR ; CANCERS ; population-based ; IMMUNOCOMPETENT INDIVIDUALS ; E6 PROTEIN ; multiplex serology ; PLUCKED EYEBROW HAIRS
    Abstract: Background. Although infection with human papillomaviruses (HPVs) is a major risk factor for several epithelial cancers, an etiologic relationship between HPV and keratinocyte cancers, such as squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), remains unclear. Methods: In a population-based case-control study of 252 SCC case patients, 525 BCC case patients, and 461 control subjects, we used multiplex serology to detect antibodies in plasma samples against 16 HPV types from phylogenetic genera alpha, beta, and mu. Multiplex serology is a new method that is based on fluorescent bead technology and allows simultaneous detection of antibodies against up to 100 different in situ affinity-purified recombinant HPV proteins. Data on sun sensitivity, outdoor exposure, and other risk factors for keratinocyte cancers were collected through personal interviews. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated via unconditional logistic regression models. Results: Overall, we detected HPV antibodies more frequently in SCC patients than in control subjects (OR = 1.6, 95% CI = 1.2 to 2.3), but we found no difference in HPV seropositivity between BCC case patients and control subjects (OR = 0.8, 95% CI = 0.6 to 1.1). Among HPV types, seropositivity to HPV types in genus beta (OR = 1.5,95% CI = 1.0 to 2.1), particularly HPV 5 (OR = 1.8,95% CI = 1.0 to 3.1), was associated with SCC risk. Individuals with tumors on chronically sun exposed sites were more likely to be seropositive for beta HPV types than individuals with SCC at other anatomic sites. The highest SCC risk was associated with positivity for multiple HPV types and, among individuals seropositive for HPV beta, a tendency to sunburn; however, the associations had limited statistical precision. Conclusions: Our findings support a role for HPV types from the genus beta in the pathogenesis of SCC
    Type of Publication: Journal article published
    PubMed ID: 16537831
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  • 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: CANCER ; Germany ; human ; CLASSIFICATION ; DIAGNOSIS ; SYSTEM ; SYSTEMS ; DISEASE ; DISEASES ; PATIENT ; DNA ; INFECTION ; papillomavirus ; ALPHA ; IDENTIFICATION ; CERVICAL-CANCER ; PCR ; REGION ; human papillomavirus ; genotyping ; HIGH-RISK ; HPV ; HUMAN-PAPILLOMAVIRUS ; sensitivity ; MANAGEMENT ; RE ; METAANALYSIS ; methods ; USA ; microbiology ; AGREEMENT ; UPSTREAM ; HPV types ; KAPPA ; COINFECTION
    Abstract: Human papillomavirus (HPV) DNA detection and typing are important for diagnosis and management of HPV-associated diseases. One of the most commonly used PCR methods, GP5+/6+, shows weaknesses in amplifying certain types. To circumvent this limitation, we developed and validated broad-spectrum primers targeting the GP5+/6+ region. The addition of eight upstream and two downstream BSGP5+/6+ (BS) primers improved amplification of plasmids of 14 genital HPV types 10- to 1,000-fold versus GP5+/6+ PCR without altering sensitivity for the 10 others. For these 24 types, an analytic sensitivity of 〈= 1,000 plasmid copies in the presence of 100 ng cellular DNA was obtained. Additionally, we integrated an internal beta-globin PCR into both HPV PCR systems, allowing simultaneous DNA quality control without affecting the sensitivity of HPV detection. Furthermore, we describe five additional low-risk HPV probes used in multiplex HPV genotyping (MPG) for simultaneous identification of all 15 high-risk, 3 putative high-risk, and 9 low-risk HPV genotypes. The performance of BSGP5+/6+ multiplexed with beta-globin primers was compared to that of standard GP5+/6+ with DNA from 1,112 cervical scrapings. There was 79% overall agreement (kappa = 0.816). BSGP5+/6+ was significantly more sensitive than GP5+/6+ for detection of HPV 30, 39, 42, 44, 51, 52, 53, 68, 73, and 82, detecting 212 additional HPV infections and increasing the proportion of multiple infections from 17.2 to 26.9% in cancer patients. In conclusion, BSGP5+/6+ multiplexed with beta-globin PCR provides an improvement in type-specific amplification sensitivity and homogeneity compared to, GP5+/6+ and offers simultaneous internal control of DNA quality. BSGP5+/6+-MPG, therefore, is suitable for epidemiologic and also diagnostic applications
    Type of Publication: Journal article published
    PubMed ID: 18199790
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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 ; EXPRESSION ; COMBINATION ; Germany ; DIAGNOSIS ; screening ; RNA ; transcription ; DNA ; INFECTION ; MARKER ; ACID ; LESIONS ; PROGRESSION ; MALIGNANCIES ; PATTERNS ; ASSAY ; WOMEN ; cervical cancer ; CERVICAL-CANCER ; TYPE-16 ; HIGH-RISK ; HPV ; TRANSFORMATION ; HUMAN KERATINOCYTES ; HUMAN-PAPILLOMAVIRUS TYPE-16 ; L1 ; specificity ; INFECTIONS ; PRECURSORS ; ONCOLOGY ; PATTERN ; papillomaviruses ; MESSENGER-RNAS ; development ; E2 PROTEIN ; transcriptome ; Lead ; Type ; OVERTREATMENT ; SEQUENCE-BASED AMPLIFICATION
    Abstract: Infections with high-risk human papillomaviruses (HPV), mainly HPV type 16, can cause malignant transformation of the human cervical epithelium and the development of cervical cancer (CxCa). A rapid and precise diagnosis of the precancerous lesions by conventional cytology or HPV DNA tests remains difficult and often leads to overtreatment. We quantitatively analyzed the HPV16 transcriptome of 80 HPV16 DNA-positive cervical scrapes classified as mild cytologic grade, including no intraepithelial lesion or malignancy (NIL/M; normal, n = 25) and low-grade squamous intraepithelial lesion (LSIL; n = 24), and severe cytologic grade, including high-grade squamous intraepithelial lesion (HSIL; n = 24) and CxCa ( n = 7), with novel nucleic acid sequence-based amplification-Luminex assays. In severe lesions, HPV16 E6*II and E1C encoding transcripts were strongly upregulated, whereas spliced E1(boolean AND)E4 and L1 encoding transcripts were markedly downregulated. Using a combination of the four marker transcripts, 100% of CxCa and 67% of HSIL cases were correctly identified as severe, and 74% of LSIL and 92% of NIL/M samples as mild cytologic grade. Compared with a commercially available HPV E6/E7 mRNA assay, the specificity of the marker combination for discriminating severe and mild cytologic lesions increased from 23% to 83%. In conclusion, we identified a novel HPV16 RNA pattern for grading of cervical lesions with a potentially high diagnostic value for the primary screening of CxCa precursors and the triage of cervical lesions. Cancer Res; 70(1); 249-56. (C) 2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20028865
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  • 7
    Keywords: EPIDEMIOLOGY ; POPULATION ; RISK ; INFECTION ; ASSOCIATION ; BETA ; RENAL-TRANSPLANT RECIPIENTS ; glutathione-S-transferase ; IMMUNOCOMPETENT INDIVIDUALS ; PREVALENT-COHORT
    Abstract: Abstract: Background Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). Methods One hundred and fifty-three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case-control study were re-contacted, and a follow-up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow-up period were ascertained. Recurrences and new second cancers were considered together as 'outcomes' in time-to-event analyses and in Cox proportional hazard models. Results Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV-24-seropositive patients with an SCC at baseline had a 4-fold increased risk of developing a subsequent SCC (hazard ratio 4.35, 95% confidence interval 1.2-15.6, P = 0.024). No association between serological status for any HPV type tested and an increased risk of BCC was found. Conclusions We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case-control studies and may spur further prospective studies on the causal role of HPVs in NMSC.
    Type of Publication: Journal article published
    PubMed ID: 21561438
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  • 8
    Keywords: CANCER ; INFECTION ; RISK-FACTORS ; ASSOCIATION ; INDIVIDUALS ; glutathione-S-transferase ; E6 PROTEINS ; SEROPOSITIVITY ; BASAL-CELL ; UV-INDUCED APOPTOSIS
    Abstract: Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n = 1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20, 23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07-3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27-1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.
    Type of Publication: Journal article published
    PubMed ID: 23536363
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  • 9
    Keywords: INFECTION ; smoking ; VIRUS-LIKE PARTICLES ; HPV TYPE-16 ; glutathione-S-transferase ; YOUNG-WOMEN ; POPULATION-BASED COHORT ; COSTA-RICA ; FEMALE UNIVERSITY-STUDENTS ; IMMUNOGLOBULIN LEVELS
    Abstract: Only a subset of women with human papillomavirus (HPV) infections will become seropositive, and the factors influencing seroconversion are not well understood. We used a multiplex serology assay in women with mildly abnormal cytology results to examine seroreactivity to oncogenic HPV genotypes. An unbiased subset of women in the atypical squamous cell of undetermined significance /low-grade squamous intraepithelial lesion Triage Study provided blood samples at trial enrollment for serological testing. A Luminex assay based on glutathione s-transferase-L1 fusion proteins as antigens was used to test seroreactivity against eight carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52 and 58). We analyzed the relationship between seroprevalence in women free of precancer (N = 2,464) and HPV DNA status, age, sexual behavior and other HPV-related risk factors. The overall seroprevalence was 24.5% for HPV16 L1 and approximately 20% for 18L1 and 31L1. Among women free of precancer, seroprevalence peaked in women less than 29 years and decreased with age. Type-specific seroprevalence was associated with baseline DNA detection for HPV16 (OR = 1.36, 95%CI: 1.04-1.79) and HPV18 (OR = 2.31, 95%CI: 1.61-3.32), as well as for HPV52 and HPV58. Correlates of sexual exposure were associated with increased seroprevalence across most genotypes. Women who were current or former smokers were less likely to be seropositive for all eight of the tested oncogenic genotypes. The multiplex assay showed associations between seroprevalence and known risk factors for HPV infection across nearly all tested HPV genotypes but associations between DNA- and serostatus were weak, suggesting possible misclassification of the participants' HPV serostatus.
    Type of Publication: Journal article published
    PubMed ID: 23588935
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  • 10
    Keywords: INFECTION ; antibody ; WOMEN ; PREVALENCE ; HUMAN-PAPILLOMAVIRUS TYPES ; SEROPREVALENCE ; HOMOSEXUAL-MEN
    Abstract: We investigated the route of sexual exposure as a determinant for human papillomavirus (HPV)-16 and HPV-18 seropositivity. At the Amsterdam sexually transmitted infections clinic we recruited 4 risk groups: (1) men who have sex with women only (MSW; n = 751); (2) women who have sex with men (WSM; n = 749); (3) men who have sex with men (MSM) reporting insertive anal sex only (insMSM; n = 156); and (4) MSM reporting receptive anal sex (recMSM; n = 415). In multivariable analyses, HPV-16 seropositivity was significantly more common in WSM vs MSW, recMSM vs MSW, and recMSM vs insMSM. HPV-18 results were similar. Route of sexual exposure is independently associated with HPV seropositivity.
    Type of Publication: Journal article published
    PubMed ID: 23861551
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