| 1. |
- Andersson, Kristin, et al.
(författare)
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Seroreactivity to Cutaneous Human Papillomaviruses among Patients with Nonmelanoma Skin Cancer or Benign Skin Lesions.
- 2008
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 17:1, s. 189-195
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Tidskriftsartikel (refereegranskat)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. (Cancer Epidemiol Biomarkers Prev 2008;17(1):189-95).
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| 2. |
- Casabonne, Delphine, et al.
(författare)
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A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:8, s. 1862-1868
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Ekström, Johanna, et al.
(författare)
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Cutaneous human papillomavirus 88: Remarkable differences in viral load.
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:2, s. 477-480
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Tidskriftsartikel (refereegranskat)abstract
- A human papillomavirus (HPV) was cloned from a patient with multiple squamous cell carcinomas (SCCs) and identified as HPV88, recently categorized into a new species within the genus Gamma. The HPV88 viral load in an SCC of the index patient exceeded 1 million copies/cell. By contrast, a survey of 447 skin lesions (79 actinic keratoses, 73 seborrhoeic keratoses, 169 basal cell carcinomas and 126 SCCs) and 362 healthy skin biopsies found detectable HPV88 DNA in only 7 specimens. All these had very low viral loads (<1 copy/10(3) cells) implying extreme biological variability in viral load.
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| 4. |
- Ekström, Johanna, et al.
(författare)
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Staphylococcus aureus and Squamous Cell Carcinoma of the Skin.
- 2009
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 18:2, s. 472-478
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Tidskriftsartikel (refereegranskat)abstract
- Squamous cell carcinoma (SCC) of the skin is a tumor with greatly increased incidence among immunosuppressed patients; therefore, an infectious cause of SCC has long been sought. We performed a hospital-based case-control study of Staphylococcus aureus and biopsies of SCC (n = 82), basal cell carcinoma (n = 142), actinic keratosis (n = 57), and seborrhoeic keratosis (n = 72) in comparison with biopsies from healthy skin of these 353 immunocompetent patients. In a S. aureus-specific PCR, targeting the nuc gene, presence of S. aureus DNA was strongly associated with SCC (29.3% positive specimens; adjusted odds ratio, 6.23; 95% confidence interval, 3.10-12.53) compared with healthy skin (5.7% positive specimens). There was also a tendency for association of S. aureus with actinic keratosis, but no association was found for basal cell carcinoma or seborrhoeic keratosis. Analysis using cotton swab samples taken on top of the lesions and from healthy skin gave similar results (adjusted odds ratio for SCC compared with healthy skin, 2.67; 95% confidence interval, 1.47-4.83). In conclusion, there is a strong association between SCC and presence of S. aureus. The study design used cannot determine whether the association implies that presence of S. aureus might influence carcinogenesis or whether it may imply that SCC has an increased susceptibility to S. aureus colonization. (Cancer Epidemiol Biomarkers Prev 2009;18(2):OF1-7).
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| 5. |
- Forslund, Ola, et al.
(författare)
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Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma
- 2007
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196, s. 876-83
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Tidskriftsartikel (refereegranskat)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.
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| 6. |
- Forslund, Ola
(författare)
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Genetic diversity of cutaneous human papillomaviruses
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88, s. 2662-2669
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomaviruses (HPVs) of the genera Betapapillomavirus and Gammapapillomavirus are common on human skin. Sequencing of subgenomic amplicons of cutaneous HPVs has revealed a large number of novel putative HPV types within these genera. Phylogenetic analysis based on these amplicons revealed 133 putative HPV types with <90% sequence identity to any known HPV type or to each other. As there are already 34 characterized HPV types described within the genera Betapapillomavirus and Gammapapillomavirus, they appear to be the most genetically diverse of the HPVs, apparently comprising at least 167 different HPV types.
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| 7. |
- Gheit, Tarik, et al.
(författare)
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Development of a sensitive and specific multiplex PCR method combined with DNA microarray primer extension to detect beta-papillomavirus types.
- 2007
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 45:8, s. 2537-2544
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Tidskriftsartikel (refereegranskat)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.
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| 8. |
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| 9. |
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| 10. |
- Handisurya, Alessandra, et al.
(författare)
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Serological relationship between cutaneous human papillomavirus types 5, 8 and 92
- 2009
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 90:1, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- Evidence of a possible association of cutaneous human papillomavirus (HPV) types, especially members of the genus Betapapillomavirus, and the development of non-melanoma skin cancer (NMSC) is accumulating. Vaccination with virus-like particles (VLPs) consisting of self-assembled L1, the major capsid protein, has been introduced to control anogenital HPV infection. This study examined the serological relationship between betapapillomavirus (beta 3-PV) types 5 and 8 and the new type HPV-92, which has recently been isolated from a basal cell carcinoma containing a high number of viral genomes. Following expression by recombinant baculoviruses, the L1 protein of HPV-92 self-assembled into VLPs that elicited high-titre antibodies after immunization, similar to VLPs from HPV-5 and -8. Haemagglutination inhibition (HAI) assays were used as a surrogate method for the detection of virion-neutralizing antibodies, which correlates with protection from infection. Antisera raised against HPV-5 and -8 VLPs displayed HAI activity not only against the homologous type, but also against heterologous HPV types 5, 8 and 92, whereas HAI activity of antisera against HPV-92 VLP was restricted to the homologous type. The results of neutralization assays using HPV-5 pseudovirions were consistent with those from HAI assays. Cross-neutralizing immune responses by VLP vaccination against heterologous HPV types may provide broader protection against the multiplicity of HPV types detected in NMSC. If a close link to HPV infection can be conclusively established, these results may provide a basis for further evaluation of VLPs of beta-PVs as candidates for a prophylactic skin-type HPV vaccine, aimed at reducing the incidence of NMSC.
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| 11. |
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| 12. |
- Hazard, Kristina, et al.
(författare)
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Cutaneous Human Papillomaviruses Persist on Healthy Skin.
- 2007
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 127:1, s. 116-119
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.
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| 13. |
- Hazard, Kristina, et al.
(författare)
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Human papillomavirus subtypes are not uncommon.
- 2007
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Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 362:1, s. 6-9
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Tidskriftsartikel (refereegranskat)abstract
- While both variants and types of human papillomavirus (HPV) are common, subtypes (2-10% sequence divergence in the L1 gene) have been considered to be rare. We searched GenBank and in-house databases using a 440 nt L1 fragment and identified 7, 30 and 10 subtypes/putative subtypes in the HPV genera Alpha, Beta and Gamma, respectively. The number of types/putative types in each genus was 54, 58 and 103. Thus, there appears to exist at least 47 different subtypes/putative subtypes of HPV and they seem to be particularly common in the genus Betapapillomavirus.
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| 14. |
- Hazard, Kristina, et al.
(författare)
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Subtype HPV38b[FA125] demonstrates heterogeneity of human papillomavirus type 38.
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:5, s. 1073-1077
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Tidskriftsartikel (refereegranskat)abstract
- The human papillomaviruses (HPVs) exist as more than 100 distinct types. While variants of HPV are common, only few HPV subtypes have been reported. HPV type 38 has been proposed to be associated with nonmelanoma skin cancer (NMSC), with reported prevalences of up to 55%. A subtype of HPV38 was cloned, completely sequenced and found to have a 96% sequence similarity to prototype HPV38 in the L1 open reading frame. The presence of prototype HPV38 and HPV38b[FA125] was examined in paired biopsies of tape-stripped skin lesions and healthy skin from 269 immunocompetent patients by real-time PCR. Prototype HPV38 and HPV38b[FA125] were present in seven (3%) and five (2%) lesions, respectively, in viral loads ranging from one copy per 150 cells to one copy per 70,000 cells. In summary, we found that HPV38 is heterogeneous and is one of so far only few HPVs that contain subtypes. The heterogeneity needs to be considered in studies of the biology of this virus. (c) 2006 Wiley-Liss, Inc.
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| 15. |
- Mistry, Nitesh, 1978-
(författare)
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Human papillomavirus tropism : determinants of viral tissue specificity
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical cancer is the second most common cancer among women worldwide and human papillomavirus (HPV) is a prerequisit for the development of this cancer. HPV belongs to the Papillomaviridae family and infects the basal layer of epithelial cells where it generally progresses into warts or condylomas. HPV can only reproduce in differentiating epithelia and it is therefore difficult to study the natural infection of HPV. More than 100 HPV types exist and they are divided into different genera based on their L1 open reading frame sequence. Most of the HPV types in the alpha-papillomavirus genus infect the mucosal epithelium while HPVs from the beta-papillomavirus genus usually infect cutaneous epithelial cells. Presently, it is not known what decides the anatomical tropism and our aim was to study determinants of this tropism. By using HPV virus like particles (VLP) and pseudovirus we found that VLPs from the two alpha-papillomaviruses HPV-6 and HPV-16 interacted with cell-surface heparan sulfate (HS) for initial attachment. When we labelled HPV VLPs with a fluorescent dye to study internalization HPV-6 was more strongly inhibited than HPV-16. Furthermore, a pseudovirus infection assay demonstrated that the beta-papillomavirus HPV-5 was less dependent on HS for infection than HPV-16. By analyzing the isoelectric point (p1) of the HPV L1 capsid protein we found that alpha HPV types were more positively charged than beta HPV types. Also, HPV-6 had a higher positive charge than HPV-16. Thus, the inhibition of the negatively charged heparin against HPV infection was clearly related to the charge of the HPV L1 capsid. This suggested that the initial interaction could be one of the determinants of tropism although not the sole factor. Lactoferrin is a protein found in milk, saliva, semen, tear fluid and endocervical secretions that has antiviral activities. Both human and bovine lactoferrin inhibited HPV infection but we found no significant differences in inhibition of alpha- and beta-papillomavirus infection. We could however demonstrate that different lactoferricins, small peptide derivates from the N-terminal part of lactoferrin, were able to inhibit HPV infection. This antiviral activity depended on lactoferricin peptide, HPV type and cell origin. The regulation of HPV gene expression in the host cell could also determine HPV tropism. The HPV long control region (LCR) contains cis-responsive elements that regulate HPV transcription and the epithelial tropism of HPV is determined by epithelial specific constitutive enhancers in the LCR. It has been hypothesized that the combination of transcription factors in the host cell determines the cell-type-specific expression. In cells with a skin origin the HPV-5 LCR was twice as efficient in transcriptional activation compared to HPV-16 LCR, while in cervical cells the HPV-16 LCR was almost twice as effective in activating transcription compared to HPV-5 LCR. To conclude, alpha- and beta-papillomaviruses differed regarding their ability to infect cells and regulate viral gene expression. These abilities corresponded with their natural host cells and suggested that HPV anatomical tropism could be determined at several steps in the HPV life cycle.
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| 16. |
- Naucler, Pontus, et al.
(författare)
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Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
- 2009
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:2, s. 88-99
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Tidskriftsartikel (refereegranskat)abstract
- Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.
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| 17. |
- Naucler, Pontus, et al.
(författare)
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Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
- 2007
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Ingår i: New England Journal of Medicine. - Boston, Massachusetts : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 357:16, s. 1589-97
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Tidskriftsartikel (refereegranskat)abstract
- Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
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| 18. |
- Paoli, John, 1975, et al.
(författare)
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Penile intraepithelial neoplasia: results of photodynamic therapy
- 2006
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Ingår i: Acta Derm Venereol. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 86:5, s. 418-21
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Tidskriftsartikel (refereegranskat)abstract
- Failure of response to treatment or recurrent disease is often noted in patients with penile intraepithelial neoplasia. Photodynamic therapy has recently been added to the list of treatment modalities used for this diagnosis. Our primary objective was to study the results of photodynamic therapy in the treatment of penile intraepithelial neoplasia in men over the age of 40 years. Ten patients aged 42-82 years with histopathologically confirmed lesions were studied. Lesions initially responded to photo-dynamic therapy in 7 out of 10 patients. Four of these patients presented no recurrences during a mean follow-up of 35 months, and were completely cleared after 2-8 treatments (mean 4.5 treatments). Three patients presented recurrences after treatment. No patient developed invasive penile cancer (mean follow-up 46.5 months). Photodynamic therapy is an alternative in the treatment of penile intraepithelial neoplasia, although prospective randomized trials are required to provide therapeutic guidelines.
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| 19. |
- Vasiljevic, Natasa, et al.
(författare)
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Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96.
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:Pt 5, s. 1479-1483
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Tidskriftsartikel (refereegranskat)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.
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| 20. |
- Vasiljevic, Natasa, et al.
(författare)
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Differences in transcriptional activity of cutaneous human papillomaviruses.
- 2008
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Ingår i: Virus Research. - : Elsevier BV. - 1872-7492 .- 0168-1702. ; Aug 6, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between UV-B irradiation and cutaneous human papillomaviruses (HPV) has been suggested to be of relevance for the development of non-melanoma skin cancers. We investigated the activity within the upstream regulatory region (URR) of the HPV types 8, 38, 92, 93 and 96, as well as their responsiveness to UV-B irradiation and cellular differentiation. Promoter activities were higher in HaCaT than in SiHa cells, corresponding to the HPV tissue tropism. Transcriptional start sites were mapped at P(92) (HPV-38), P(45) (HPV-92), P(7439) (HPV-93) and P(256) (HPV-96). Transcription from HPV-8, 93 and 96 URR was up-regulated by cellular differentiation, linking the activity of these HPVs to the cellular state. UV-B irradiation activated HPV-8 but inhibited HPV-38 and HPV-93 whereas HPV-92 and 96 were not affected. As there are variable UV-B responses among the HPV types, further studies of interactions between UV-B and HPV need to consider the HPV type.
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| 21. |
- Vasiljevic, Natasa, et al.
(författare)
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Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis.
- 2008
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 89:Pt 10, s. 2467-2474
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have suggested an association between human papillomaviruses (HPVs), particularly species 2 members of the genus Betapapillomavirus, and squamous cell carcinoma (SCC) of the skin. As most of these viruses are uncharacterized, molecular characterization and epidemiology are needed to advance our understanding of their significance in carcinogenesis. This study determined the complete genomes of four betapapillomaviruses of species 2 from skin lesions designated HPV-107, -110 and -111 and FA75[KI88-03], an isolate of an unpublished HPV type, and analysed their prevalence and viral loads in biopsies from SCC, actinic keratosis (AK), basal cell carcinoma, seborrhoeic keratosis and the healthy skin of 263 immunocompetent patients by HPV type-specific real-time PCR assays. Seventeen patients (6.5 %) harboured at least one of the four HPV types in their lesion, whereas seven patients (2.7 %) harboured one or more of the HPV types in healthy skin. Overall, the four viruses were more common in AK than in healthy skin (odds ratio 5.0, 95 % confidence interval 1.4-17.5), but the prevalence and viral loads were low. This characterization of HPV-107, -110 and -111 and FA75[KI88-03] expands the heterogeneity of members of species 2 of the genus Betapapillomavirus. However, as these types were found in only a few samples and in low amounts, a possible role in carcinogenesis remains elusive.
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| 22. |
- Vasiljevic, Natasa, et al.
(författare)
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The Bcl-xL inhibitor of apoptosis is preferentially expressed in cutaneous squamous cell carcinoma compared with that in keratoacanthoma.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124, s. 2361-2366
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Tidskriftsartikel (refereegranskat)abstract
- Keratoacanthoma (KA) is difficult to histologically distinguish from squamous cell carcinoma (SCC). Therefore, although KA is a benign self-resolving skin lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would thus be desirable. In search for specific markers, paraffin-embedded tissue samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and stained for immunologic cell-markers CD3, CD20 and CD68 as well as for proteins considered of relevance in tumorgenesis, namely NFkappaB/p65, IkappaB-alpha, STAT3, p53, TRAP-1, pRB, phosphorylated pRb, Cyld, p21, p16(INK4), Survivin, Bcl-xL, Caspase 3, Bak, FLK-1/VEGF-r2 and Ki-67. In addition, the tumors were tested for presence of human papillomavirus by PCR. We detected that the two lesions differed significantly in expression of Bcl-xL which was present in 84% of the SCC compared with only 15% in the KA (p < 0.001). The lower expression of the antiapoptotic protein Bcl-xL in KA is consistent with a possible role of apoptosis in the regression of KA. (c) 2008 Wiley-Liss, Inc.
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