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  • 1
    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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  • 2
    Keywords: CELLS ; CELL ; human ; MODEL ; GENOME ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; TUMORS ; PATIENT ; DNA ; INFECTION ; CARCINOGENESIS ; tumour ; SKIN ; BINDING ; E7 ; OPEN READING FRAME ; SEQUENCES ; skin carcinogenesis ; PCR ; SWEDEN ; HPV ; INFECTIONS ; NONMELANOMA SKIN CANCERS ; real-time PCR ; BIOPSY ; RETINOBLASTOMA PROTEIN ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; REAL-TIME ; E6 PROTEINS ; microbiology ; ENGLAND ; HUMAN PAPILLOMAVIRUSES ; retinoblastoma ; BIOPSIES ; E7 PROTEIN ; viral ; virology ; biotechnology ; GENOMES ; HPV types ; HPV DNA ; HEALTHY SKIN ; MALIGNANT-TRANSFORMATION
    Abstract: Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The Ll open reading frame of HPV93 showed highest identity to HPV24 (79%) and that of HPV96 had highest identity to HPV92 (71 %). Real-time PCR for HPV92, 93 and 96 on stripped biopsies from tumours and healthy skin from 269 immunocompetent patients found HPV DNA in 2.6 % of tumours and in 0.4 % of healthy skin samples. Double infections were observed in two tumours. HPV92 was detected in four, HPV93 in two and HPV96 in three tumours. The range of viral loads spanned from one copy per 45 cells to one copy per 10 000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study,
    Type of Publication: Journal article published
    PubMed ID: 17412976
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  • 3
    Abstract: Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil) or bivalent (Cervarix) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix, all subjects became seropositive for HPV16 and 18. After Gardasil vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were 〈1 international unit (IU) in 87% of study subjects before vaccination but 〉10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil vaccination for 〉50% of vaccinated females for HPV 31, 35 and 73 and for 〉50% of Cervarix-vaccinated females for HPV 31, 33, 35, 45, 56 and 58. Cross-reactivity with non-genital HPV types was also detected. In conclusion, HIV-infected subjects responded to HPV vaccination with induction of neutralizing antibodies against both vaccine and non-vaccine types.
    Type of Publication: Journal article published
    PubMed ID: 26896686
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  • 4
    Keywords: SPECTRA ; CANCER ; carcinoma ; CELL ; human ; MODEL ; MODELS ; DISEASE ; DISEASES ; RISK ; SITE ; SITES ; SAMPLE ; SAMPLES ; PATIENT ; DNA ; INFECTION ; RISK-FACTORS ; SKIN ; LESIONS ; risk factors ; skin cancer ; PATHOGENESIS ; PCR ; SWEDEN ; HPV ; BENIGN ; MULTIVARIATE ; CARCINOMAS ; squamous cell carcinoma ; PREVALENCE ; RENAL-TRANSPLANT RECIPIENTS ; BIOPSY ; SKIN-CANCER ; basal cell carcinoma ; CELL CARCINOMA ; INTERVAL ; methods ; ACTINIC KERATOSES ; USA ; odds ratio ; RISK-FACTOR ; CANCERS ; E ; SPECTRUM ; SQUAMOUS-CELL ; HERPES-SIMPLEX ; HUMAN PAPILLOMAVIRUSES ; BIOPSIES ; HPV types ; ULTRAVIOLET-IRRADIATION
    Abstract: Background. A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. Methods. We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples-from the lesion and from healthy skin from the same patient-were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. Results. Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44-8.111) and for the healthy skin samples (OR, 3.65 [95% CI 1.79-7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92-10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72-6.99]). Conclusions. Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma
    Type of Publication: Journal article published
    PubMed ID: 17703418
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  • 5
    Keywords: DNA ; LESIONS ; CERVICAL-CANCER ; HIGH-RISK ; SQUAMOUS-CELL CARCINOMA ; glutathione-S-transferase ; IMMUNOCOMPETENT INDIVIDUALS ; SEROPOSITIVITY ; CUTANEOUS HUMAN PAPILLOMAVIRUSES ; SEROREACTIVITY
    Abstract: Genital high-risk human papillomaviruses (HPVs) cause cervical cancer and are also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used cancer registry linkages to follow the 856,000 serum donors included in the Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident skin cancers occurring up to 30 years after serum donation. Serum samples taken before diagnosis of squamous cell carcinoma (SCC) (N = 633), basal cell carcinoma (BCC) (N = 1990) or other NMSC (N = 153) and matched samples from control donors were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18 were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.6 and OR 1.7, 95% CI 1.1-2.5, respectively] and other NMSC (OR 2.3, 95% CI 1.0-5.2 and OR 3.5, 95% CI 1.4-8.7, respectively), but not for BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real-time polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found and only four of 79 SCC cases (two of which were from the perineum/perianal area), one of 221 BCC cases and zero of five cases with other NMSC contained HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18 antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only a small proportion of seropositive subjects had evidence of the corresponding HPV DNA in the tumor, most of this excess risk is likely to be due to confounders associated with genital HPV infection.
    Type of Publication: Journal article published
    PubMed ID: 23553409
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  • 6
  • 7
    Keywords: human ; CLASSIFICATION ; DNA ; SEQUENCE ; FREQUENCY ; virus ; LESIONS ; SWEDEN ; BENIGN ; CARCINOMAS ; INFECTIONS ; PREVALENCE ; HPV,NMSC,quantification,PCR,BCC,SCC,solar keratosis,complete genome ; human papilloma virus ; NONMELANOMA SKIN CANCERS ; RENAL-TRANSPLANT RECIPIENTS ; VERRUCIFORMIS-ASSOCIATED TYPES
    Type of Publication: Journal article published
    PubMed ID: 12919731
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  • 8
    Keywords: SPECTRA ; CANCER ; human ; GENE ; HYBRIDIZATION ; microarray ; SAMPLE ; SAMPLES ; LINES ; DNA ; SKIN ; E7 ; papillomavirus ; AMPLIFICATION ; ASSAY ; skin cancer ; LINE ; PCR ; human papillomavirus ; HPV ; BETA ; DIVERSITY ; HUMAN-PAPILLOMAVIRUS ; sensitivity ; MUTATION DETECTION ; SKIN-CANCER ; SINGLE ; RE ; EXTENSION ; ARRAY ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; development ; INTERVAL ; methods ; DNA-MICROARRAY ; technique ; USA ; PRIMER EXTENSION ; SPECTRUM ; microbiology ; BIOPSIES ; HUMAN-PAPILLOMAVIRUS TYPES ; MUCOSAL ; HPV types ; KAPPA
    Abstract: Emerging lines of evidence indicate that the cutaneous human papillomavirus (HPV) types that belong to the genus Betapapillomavirus (beta HPV) are involved in the development of nonmelanoma skin cancer. Unlike the situation for mucosal HPV types, highly sensitive and reliable methods to identify characterized cutaneous HPV types in a single assay are limited. Here, we describe a novel one-shot method for the detection of all characterized beta HPV types, namely, HPV type 5 (HPV5), 8, 9, 12, 14, 15, 17, 19, 20, 21, 22, 23, 24, 25, 36, 37, 38, 47, 49, 75, 76, 80, 92, 93, and 96. This assay combines two different techniques: multiplex PCR using HPV type-specific primers for amplification of each E7 gene and array primer extension (APEX) for typing. This method has been validated using clinical samples which were analyzed simultaneously for the presence of cutaneous HPV types by two additional methods, i.e., the FAP59/64 PCR protocol and a commercially available PCR-reverse hybridization assay (PM-PCR RHA). Our data show good agreement between the results obtained with the multiplex PCR/APEX assay and the PM-PCR RHA method (overall HPV positivity of 92.2% for multiplex PCR/APEX assay versus 90.6% with the PM-PCR RHA) (kappa value, 50; 95% confidence interval, 13 to 88). In addition, the multiplex PCR/APEX assay showed higher sensitivity than the PM-PCR RHA did. This favorable feature and the high-throughput potential make this assay ideal for large-scale clinical and epidemiological studies aimed at determining the spectrum of cutaneous types in skin cancer
    Type of Publication: Journal article published
    PubMed ID: 17581938
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  • 9
    Keywords: CANCER ; carcinoma ; CELL ; human ; DISEASE ; CLONING ; PROTEIN ; PATIENT ; DNA ; INFECTION ; MARKER ; RISK-FACTORS ; SKIN ; E7 ; antibodies ; antibody ; virus ; LESIONS ; HEALTH ; ASSAY ; skin cancer ; PCR ; SWEDEN ; CAPSID PROTEIN ; HPV ; SQUAMOUS-CELL CARCINOMA ; ONCOPROTEIN ; CANCER-PATIENTS ; CARCINOMAS ; squamous cell carcinoma ; INDIVIDUALS ; L1 ; sensitivity ; PREVALENCE ; NONMELANOMA SKIN CANCERS ; RENAL-TRANSPLANT RECIPIENTS ; CANCER PATIENTS ; HEALTHY ; BIOPSY ; SKIN-CANCER ; basal cell carcinoma ; glutathione-S-transferase ; SERUM ; CELL CARCINOMA ; ONCOLOGY ; papillomaviruses ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; biomarker ; ACTINIC KERATOSES ; USA ; cancer research ; CANCERS ; SQUAMOUS-CELL ; serology ; HUMAN PAPILLOMAVIRUSES ; SEROPREVALENCE ; HPV types ; BASAL-CELL ; biological ; MAJOR CAPSID PROTEIN
    Abstract: Cutaneous human papillomaviruses (HPV) are common in nonmelanoma skin cancers, benign skin lesions, and healthy skin. Increased seroprevalences for cutaneous HPV among nonmelanoma skin cancer patients have been described. To determine whether antibodies to cutaneous HPV are related to presence of the virus and/or to skin disease, we collected serum and biopsies from both lesions and healthy skin from 434 nonimmunosuppressed patients (72 squamous cell carcinomas, 160 basal cell carcinomas, 81 actinic keratoses, and 121 benign lesions). Biopsies were analyzed for HPV DNA by PCR, cloning, and sequencing. Serum antibodies to the major capsid protein L1 of HPV 1, 5, 6, 8, 9, 10, 15, 16, 20, 24, 32, 36, 38, and 57 as well as to the oncoproteins E6 and E7 of HPV 8 and 38 were detected using a multiplexed fluorescent bead- based assay. Type-specific seroprevalence among patients with the same type of HPV DNA (sensitivity of serology) varied from 0% to at most 28%. Presence of HPV DNA and antibodies to the same HPV type was not significantly correlated. However, seropositivity to any HPV type was significantly more common among patients positive for HPV DNA of any HPV type (odds ratio, 1.90; 95% confidence interval, 1.55-2.34). Seroprevalences were similar among the different patient groups but was, for most HPV types, somewhat higher among squamous cell carcinoma patients than among basal cell carcinoma patients (P 〈 0.01). In conclusion, additional studies are required to clarify the biological meaning of seropositivity as a marker of cutaneous HPV infection and skin disease
    Type of Publication: Journal article published
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  • 10
    Keywords: carcinoma ; ASSAY ; BETA ; BENIGN ; NONMELANOMA SKIN CANCERS ; RENAL-TRANSPLANT RECIPIENTS ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; nested PCR ; HPV types ; DNA LOADS
    Abstract: Cutaneous human papillomaviruses (HPVs) are a heterogeneous, nonmonophyletic assembly, comprising about 50 characterized types and at least 133 isolates putatively representing new types. Their natural history of infection and potential association with nonmelanoma skin cancer are not well understood. Several PCR systems have been developed that amplify a broad spectrum of cutaneous HPVs. However, amplicon genotyping by sequencing or reverse line blot assays are complex and not well suited for high-throughput analyses. We developed a novel multiplex cutaneous papillomavirus genotyping (McPG) assay for 38 defined and 20 putative cutaneous HPVs of the beta, gamma, mu, and nu genera. Viral DNA was amplified by the use of a modified single-tube nested "hanging-droplet" FAP PCR. The amplifiable papillomavirus (PV) spectrum was enlarged by the use of 9 outer and 13 inner primers. Biotinylated PCR products were hybridized to type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads and analyzed using Luminex technology. Analytical sensitivity was analyzed for 38 defined HPVs and was 〈= 100 genome copies for all types. Integrated beta-globin primers allow for simultaneous DNA quality control. McPG is characterized by high reproducibility (kappa = 0.84, 95% confidence interval = 0.79 to 0.88), good concordance with the original nested FAP PCR, followed by sequencing (70.2% complete or partial agreement) when 322 skin biopsy DNA samples were analyzed, and improved ability to detect multiple infections (on average 2.5 HPV types per HPV-positive sample compared to 1.7 HPV types with nested FAP-PCR). In conclusion, McPG is a powerful tool for genotyping multiple cutaneous HPVs in a high-throughput format and is thus suitable for large-scale epidemiological studies
    Type of Publication: Journal article published
    PubMed ID: 21832015
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