| 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. |
- Andrae, Bengt, et al.
(författare)
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Screening-preventable cervical cancer risks : evidence from a nationwide audit in Sweden.
- 2008
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Ingår i: J Natl Cancer Inst. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 100:9, s. 622-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program.Methods: We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided.Results: Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (Phomogeneity = .96). The risk for nonsquamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer.Conclusions: Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against nonsquamous cancers.
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| 3. |
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| 4. |
- Arbyn, Marc, et al.
(författare)
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Clinical applications of HPV testing: A summary of meta-analyses
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:Suppl. 3, s. 78-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. Material and methods: A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Results: Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recur-rent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening. Conclusions: Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway. (c) 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Arbyn, M, et al.
(författare)
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Clinical utility of HPV-DNA detection: Triage of minor cervical lesions, follow-up of women treated for high-grade CIN: An update of pooled evidence.
- 2005
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 99:3, Suppl 1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Human papilloma virus (HPV) testing and repeat cytology are both proposed as methods to triage women with minor cytological cervical lesions. By triage, those women can be identified who need referral for diagnostic exploration with colposcopy and/or biopsy. Methods. We conducted meta-analyses of reported studies on the accuracy to detect high-grade cervical intra-epithelial neoplasia or worse disease (CIN2+) in women with ASCUS or LSIL. We also performed meta-analyses to examine the best predictor of recurrence of CIN after treatment for CIN2 or CIN3. Results. We found that HPV testing using the Hybrid Capture II test is more effective (more sensitive, equally specific) than cytology for the triage of patients with ASCUS Pap smears. Because of the high rate of HPV positivity, this is not the case for patients with LSIL. Studies concerning post-treatment follow-Lip were heterogeneous. In general, HPV testing performed better than follow-up cytology to predict success or failure of treatment (significantly higher sensitivity, not significantly lower specificity). Conclusions. Overall, in comparison with follow-up cytology, HPV DNA testing is more sensitive and equally specific for triage of ASCUS cases and for predicting recurrence of CIN in women treated for high-grade CIN.
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| 6. |
- Arbyn, M, et al.
(författare)
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Methods for screening and diagnosis
- 2007
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Ingår i: 2nd edition of the EU Guidelines for cervical cancer screening. - 9789279076985 ; , s. 69-141
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Arbyn, Marc, et al.
(författare)
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Review of current knowledge on HPV vaccination: An Appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening.
- 2007
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 38:3, s. 189-197
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Forskningsöversikt (refereegranskat)abstract
- The recognition of a strong etiological relationship between infection with high-risk human papillomavirusses and cervical cancer has prompted research to develop and evaluate prophylactic and therapeutic vaccines. One prophylactic quadrivalent vaccine using L1 virus-like particles (VLP) of HPV 6, 11, 16 and 18 is available on the European market since the end of 2006 and it is expected that a second bivalent vaccine containing VLPs of HPV 16 and HPV 18 will become available in 2007. Each year, HPV 16 and HPV 18 cause approximately 43,000 cases of cervical cancer in the European continent. Results from the phase-IIb and III trials published thus far indicate that the L1 VLP HPV vaccine is safe and well-tolerated. It offers HPV-naive women a very high level of protection against HPV persistent infection and cervical intra-epithelial lesions associated with the types included in the vaccine. HPV vaccination should be offered to girls before onset of sexual activity. While prophylactic vaccination is likely to provide important future health gains, cervical screening will need to be continued for the whole generation of women that is already infected with the HPV types included in the vaccine. Phase IV studies are needed to demonstrate protection against cervical cancer and to verify duration of protection, occurrence of replacement by non-vaccine types and to define future policies for screening of vaccinated cohorts. The European Guidelines on Quality Assurance for Cervical Cancer Screening provides guidance for secondary prevention by detection and management of precursors lesions of the cervix. The purpose of the appendix on vaccination is to present Current knowledge. Developing guidelines for future use of HPV vaccines in Europe, is the object of a new grant offered by the European Commission. (C) 2006 Elsevier B.V. All rights reserved.
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| 8. |
- Arbyn, Marc, et al.
(författare)
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Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate
- 2009
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 13:4, s. 648-659
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Forskningsöversikt (refereegranskat)abstract
- Introduction Methods Results Discussion Conclusion Consistent evidence underlines the utility of human papillomavirus (HPV) DNA testing in the management of women with equivocal cervical cytological abnormalities, but not in case of low-grade lesions. We performed a meta-analysis including studies where the high-risk probe of the Hybrid Capture-II is used to triage these two cytological categories. The triage test-positivity rate reflects the colposcopy referral workload.Data were pooled on the HPV test positivity rate in women with atypical squamous cells of undetermined significance (ASCUS/ASC-US) or low-grade squamous intraepithelial lesions (LSIL), derived from different cytological classification systems. The meta-analysis was restricted to studies, published between 1991 and 2007. A random-effect model was applied for meta-analytical pooling and the influence of covariates on the HPV positivity rate was analyzed by meta-regression. The variation by age was assessed within individual studies since age strata were not defined uniformly. On an average, 43% (95% CI: 40-46%) of women with ASCUS/ASC-US were high-risk HPV positive (range 23-74%). In women with LSIL, the pooled positivity rate was 76% (95% CI: 71-81%; range 55-89%). In spite of considerable inter-study heterogeneity, the difference in HPV positivity between the two triage groups was large and highly significant: 32% (95% CI: 27-38%). HPV rates dropped tremendously as age and cutoffs of test positivity increased. Other factors (cytological classification system, country, continent, collection method and year of publication) had no statistically significant impact, except in LSIL triage where HPV positivity was significantly lower in European compared to American studies. Women with LSIL, especially younger women, have high HPV positivity rates suggesting limited utility of reflex HPV triaging these cases. Research is needed to identify more specific methods to triage women with low-grade squamous cervical lesions.
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| 9. |
- Arnheim, L, et al.
(författare)
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A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia
- 2005
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Ingår i: Tissue Antigens. - Copenhagen : Blackwell Munksgaard. - 0001-2815 .- 1399-0039. ; 65:3, s. 252-259
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are involved both in control of virus infections and in elimination of tumor cells. Killer immunoglobulin-like receptors (KIRs) either activate or inhibit NK cell-mediated cytolysis, protecting healthy cells from destruction while enabling killing of abnormal cells. To investigate whether KIR genes or genotypes are associated with cervical carcinogenesis, a nested case-control study of 65 case women with cervical intraepithelial neoplasia (CIN) diagnosed during a 6-year follow-up of 15,234 women and 150 control women from the same cohort that remained healthy was performed. More than 70 different genotypes were observed, and 33 of which had not been described previously. An A-genotype including KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR3DL3, and KIR2DS4 was associated with increased risk of CIN (OR 6.7; 95% CI 1.7-26.3), and KIR2DL5B*002 appeared to have an inverse association with disease (OR 0.5; 95% CI 0.5-2.9). There was no association of CIN with the number of activating KIR genes. There was also no association between KIR genes and type of human papilloma virus or with other CIN-related immune response genes. It was concluded that certain KIR genes and genotypes may associate with cervical neoplasia.
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| 10. |
- Bistoletti, P., et al.
(författare)
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Cost-effectiveness of primary cytology and HPV DNA cervical screening
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:2, s. 372-376
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Tidskriftsartikel (refereegranskat)abstract
- Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3-5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly. © 2007 Wiley-Liss, Inc.
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