| 1. |
- Nurkkala, Merja, 1966, et al.
(author)
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Conjugation of HPV16 E7 to cholera toxin enhances the HPV-specific T-cell recall responses to pulsed dendritic cells in vitro in women with cervical dysplasia
- 2010
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:36, s. 5828-5836
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Journal article (peer-reviewed)abstract
- We have evaluated whether cholera toxin (CT) as a carrier/adjuvant can enhance human T-cell responses to a viral oncoprotein in vitro using dendritic cells (DCs) as antigen-presenting cells. Monocyte-derived DCs obtained from women with cervical dysplasia were pulsed with the HPV16 oncoprotein E7, either alone or conjugated to CT, and tested for their ability to induce antigen-specific activation of autologous T cells in vitro. CT-conjugation of E7 significantly improved the capacity of pulsed DCs to activate antigen-specific CD4+ T-cell proliferation and IFN-gamma secretion. The CT-E7-pulsed DCs also produced significantly more of the Th1-inducing cytokine IL-12 compared to DCs pulsed with E7 or CT alone. Furthermore, DCs pulsed with CT-conjugated HPV16 E7 caused a response in T cells from women with advanced disease (CIN III) as well as in T cells from women that were currently not infected with HPV16. These data show the potential of using CT-conjugated viral oncoproteins for DC-induced T-cell activation in humans.
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| 2. |
- Semb, Gunvor, et al.
(author)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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In: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 3. |
- Aarnio, Riina, 1971-, et al.
(author)
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Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+ : a randomized study
- 2021
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 148:12, s. 3051-3059
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Journal article (peer-reviewed)abstract
- Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.
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| 4. |
- Aarnio, Riina, 1971-, et al.
(author)
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Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study
- 2020
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Journal article (other academic/artistic)abstract
- BackgroundHuman papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.MethodsA cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).ResultsSelf-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). ConclusionsThis study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.
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| 5. |
- Aarnio, Riina, et al.
(author)
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Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology
- 2019
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In: European journal of obstetrics & gynecology and reproductive biology: X. - : Elsevier BV. - 2590-1613. ; 3
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Journal article (peer-reviewed)abstract
- Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.
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| 6. |
- Ameur, Adam, et al.
(author)
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Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing
- 2014
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4, s. 4398-
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Journal article (peer-reviewed)abstract
- Infections by HIV increase the risk of acquiring secondary viral and bacterial infections and methods are needed to determine the spectrum of co-infections for proper treatment. We used rolling circle amplification (RCA) and Ion Proton sequencing to investigate the vaginal microbiome of 20 HIV positive women from South Africa. A total of 46 different human papillomavirus (HPV) types were found, many of which are not detected by existing genotyping assays. Moreover, the complete genomes of two novel HPV types were determined. Abundance of HPV infections was highly correlated with real-time PCR estimates, indicating that the RCA-Proton method can be used for quantification of individual pathogens. We also identified a large number of other viral, bacterial and parasitic co-infections and the spectrum of these co-infections varied widely between individuals. Our method provides rapid detection of a broad range of pathogens and the ability to reconstruct complete genomes of novel infectious agents.
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| 7. |
- Andersson, Sonia, et al.
(author)
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Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females : A retrospective database study
- 2014
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In: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:4, s. 1528-1532
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Journal article (peer-reviewed)abstract
- Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.
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| 8. |
- Arvidsson, Johan, et al.
(author)
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Intervju med Ivar Johansson, bibliotekarie i Veddige
- 1975
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Other publication (other academic/artistic)abstract
- Interview with librarian Ivar Johansson from Veddige. The interview was conducted by Johan Arvidsson, Bengt Gustavsson, Rune Niklasson, Inger Vold Jackson and Ingrid Börjesson, students of the Swedish School of Library and Information Science in Borås, in 1975.
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| 9. |
- Arvidsson, Johan, et al.
(author)
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Intervju med Åke Hendberg, vaktmästare på Folkets hus i Varberg
- 1975
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Other publication (pop. science, debate, etc.)abstract
- Interview with Åke Hendberg, janitor of Folkets hus in Varberg. The interview was conducted by Johan Arvidsson, Bengt Gustavsson, Rune Niklasson, Inger Vold Jackson and Ingrid Börjesson, students of the Swedish School of Library and Information Science in Borås, in 1975.
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| 10. |
- Berggrund, Malin, et al.
(author)
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HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.
- 2019
-
In: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 16
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study.RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.
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| 11. |
- Berggrund, Malin, et al.
(author)
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Protein Detection Using the Multiplexed Proximity Extension Assay (PEA) from Plasma and Vaginal Fluid Applied to the Indicating FTA Elute Micro Card™
- 2016
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In: Journal of Circulating Biomarkers. - : SAGE Publications. - 1849-4544. ; 5
-
Journal article (peer-reviewed)abstract
- The indicating FTA elute micro card? has been developed to collect and stabilize the nucleic acid in biological samples and is widely used in human and veterinary medicine and other disciplines. This card is not recommended for protein analyses, since surface treatment may denature proteins. We studied the ability to analyse proteins in human plasma and vaginal fluid as applied to the indicating FTA elute micro card? using the sensitive proximity extension assay (PEA). Among 92 proteins in the Proseek Multiplex Oncology Iv2 panel, 87 were above the limit of detection (LOD) in liquid plasma and 56 among 92 above LOD in plasma applied to FTA cards. Washing and protein elution protocols were compared to identify an optimal method. Liquid-based cytology samples showed a lower number of proteins above LOD than FTA cards with vaginal fluid samples applied. Our results demonstrate that samples applied to the indicating FTA elute micro card? are amendable to protein analyses, given that a sensitive protein detection assay is used. The results imply that biological samples applied to FTA cards can be used for DNA, RNA and protein detection.
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| 12. |
- Berggrund, Malin, et al.
(author)
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Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2
- 2020
-
In: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 17
-
Journal article (peer-reviewed)abstract
- BackgroundThe vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.MethodsIn total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software.ResultsK-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).ConclusionsThe vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
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| 13. |
- Chen, Dan, et al.
(author)
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Genome-wide Association Study of Susceptibility Loci for Cervical Cancer
- 2013
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:9, s. 624-633
-
Journal article (peer-reviewed)abstract
- Background Cervical carcinoma has a heritable genetic component, but the genetic basis of cervical cancer is still not well understood. Methods We performed a genome-wide association study of 731 422 single nucleotide polymorphisms (SNPs) in 1075 cervical cancer case subjects and 4014 control subjects and replicated it in 1140 case subjects and 1058 control subjects. The association between top SNPs and cervical cancer was estimated by odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression. All statistical tests were two-sided. Results Three independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were associated with cervical cancer: the first is adjacent to the MHC class I polypeptide-related sequence A gene (MICA) (rs2516448; OR = 1.42, 95% CI = 1.31 to 1.54; P = 1.6 x 10(-18)); the second is between HLA-DRB1 and HLA-DQA1 (rs9272143; OR = 0.67, 95% CI = 0.62 to 0.72; P = 9.3 x 10(-24)); and the third is at HLA-DPB2 (rs3117027; OR=1.25, 95% CI = 1.15 to 1.35; P = 4.9 x 10(-8)). We also confirmed previously reported associations of B*0702 and DRB1*1501-DQB1*0602 with susceptibility to and DRB1*1301-DQA1*0103-DQB1*0603 with protection against cervical cancer. The three new loci are statistically independent of these specific human leukocyte antigen alleles/haplotypes. MICA encodes a membrane-bound protein that acts as a ligand for NKG2D to activate antitumor effects. The risk allele of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) of MICA, which results in a truncated protein. Functional analysis shows that women carrying this mutation have lower levels of membrane-bound MICA. Conclusions Three novel loci in the MHC may affect susceptibility to cervical cancer in situ, including the MICA-A5.1 allele that may cause impaired immune activation and increased risk of tumor development.
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| 14. |
- Crespo, Leonardo, et al.
(author)
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A systematic review of rye (Secale cereale L.) as a source of resistance to pathogens and pests in wheat (Triticum aestivum L.)
- 2017
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In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 154, s. 1-9
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Research review (peer-reviewed)abstract
- Wheat is globally one of the most important crops. With the current human population growth rate, there is an increasing need to raise wheat productivity by means of plant breeding, along with development of more efficient and sustainable agricultural systems. Damage by pathogens and pests, in combination with adverse climate effects, need to be counteracted by incorporating new germplasm that makes wheat more resistant/tolerant to such stress factors. Rye has been used as a source for improved resistance to pathogens and pests in wheat during more than 50 years. With new devastating stem and yellow rust pathotypes invading wheat at large acreage globally, along with new biotypes of pest insects, there is renewed interest in using rye as a source of resistance. Currently the proportion of wheat cultivars with rye chromatin varies between countries, with examples of up to 34%. There is mainly one rye source, Petkus, that has been widely exploited and that has contributed considerably to raise yields and increase disease resistance in wheat. Successively, the multiple disease resistances conferred by this source has been overcome by new pathotypes of leaf rust, yellow rust, stem rust and powdery mildew. However, there are several other rye sources reported to make wheat more resistant to various biotic constraints when their rye chromatin has been transferred to wheat. There is also development of knowledge on how to produce new rye translocation, substitution and addition lines. Here we compile information that may facilitate decision making for wheat breeders aiming to transfer resistance to biotic constraints from rye to elite wheat germplasm.
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| 15. |
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| 16. |
- Crespo, Leonardo, et al.
(author)
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Mapping resistance to the bird cherry-oat aphid and the greenbug in wheat using sequence-based genotyping
- 2014
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In: TAG Theoretical and Applied Genetics. - : Springer Science and Business Media LLC. - 0040-5752 .- 1432-2242. ; 127, s. 1963-1973
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Journal article (peer-reviewed)abstract
- Identification of novel resistance QTL against wheat aphids. First QTL-resistance report for R. padi in wheat and chromosome 2DL for S. graminum . These sources have potential use in wheat breeding.The aphids Rhopalosiphum padi and Schizaphis graminum are important pests of common wheat (Triticum aestivum L.). Characterization of the genetic bases of resistance sources is crucial to facilitate the development of resistant wheat cultivars to these insects. We examined 140 recombinant inbred lines (RILs) from the cross of Seri M82 wheat (susceptible) with the synthetic hexaploid wheat CWI76364 (resistant). RILs were phenotyped for R. padi antibiosis and tolerance traits. Phenotyping of S. graminum resistance was based on leaf chlorosis in a greenhouse screening and the number of S. graminum/tiller in the field. RILs were also scored for pubescence. Using a sequence-based genotyping method, we located genomic regions associated with these resistance traits. A quantitative trait locus (QTL) for R. padi antibiosis (QRp.slu.4BL) that explained 10.2 % of phenotypic variation was found in chromosome 4BL and located 14.6 cM apart from the pubescence locus. We found no association between plant pubescence and the resistance traits. We found two QTLs for R. padi tolerance (QRp.slu.5AL and QRp.slu.5BL) in chromosomes 5AL and 5BL, with an epistatic interaction between a locus in chromosome 3AL (EnQRp.slu.5AL) and QRp.slu.5AL. These genomic regions explained about 35 % of the phenotypic variation. We re-mapped a previously reported gene for S. graminum resistance (putatively Gba) in 7DL and found a novel QTL associated with the number of aphids/tiller (QGb.slu-2DL) in chromosome 2DL. This is the first report on the genetic mapping of R. padi resistance in wheat and the first report where chromosome 2DL is shown to be associated with S. graminum resistance.
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| 17. |
- Cui, Tao, 1982-, et al.
(author)
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Invasive cervical tumors with high and low HPV titer represent molecular subgroups with different disease etiology
- 2019
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 40:2, s. 269-278
-
Journal article (peer-reviewed)abstract
- Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n = 49) were classified into high- and low-HPV-titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA sequencing, and the results were validated using the AmpliSeq Transcriptome assay. HPV DNA genotyping and RNA sequencing showed that 16.6% of ICC tumors contained very low levels of HPV DNA and HPV transcripts. Tumors with low HPV levels had more mutations with a high allele frequency and fewer mutations with low allele frequency relative to tumors with high HPV titer. A number of genes showed significant expression differences between HPV titer groups, including genes with somatic mutations. Gene ontology and pathway analyses implicated the enrichment of genes involved in DNA replication, cell cycle control and extracellular matrix in tumors with low HPV titer. The results indicate that in low titer tumors, HPVs act as trigger of cancer development whereas somatic mutations are clonally selected and become drivers of the tumor development process. In contrast, in tumors with high HPV titer the expression of HPV oncoproteins plays a major role in tumor development and the many low frequency somatic mutations represent passengers. This putative subdivision of invasive cervical tumors may explain the higher radiosensitivity of ICC tumors with high HPV titer and thereby have consequences for clinical management.
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| 18. |
- Engelmark, Malin, et al.
(author)
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Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis
- 2008
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 123:5, s. 437-443
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Journal article (peer-reviewed)abstract
- Cervical cancer is a multifactorial disease influenced by both environmental and genetic factors. We have previously found linkage to 9q32 in a genomewide scan of affected sib-pairs (ASPs) with cervical cancer and to the thymic stromal co-transporter (TSCOT), a candidate gene in this region. Here we examined the contribution of 9q32 and TSCOT to cervical cancer susceptibility using at larger material of 641 ASPs, 278 of which were included in the earlier genome-scan. Since heritable forms of cancer frequently show stronger genetic effects in families with early onset of disease, we stratified the ASPs into two groups based on mean age at diagnosis (MAAD) within sib-pairs. Surprisingly, ASPs with high MAAD (30.5-47.5 years) showed increased sharing at all microsatellite markers at 9q31.1-33.1 and linkage signals of up to MLS = 2.74 for TSCOT SNPs, while ASPs with low MAAD (19-30 years) showed no deviation from random genetic sharing (MLS = 0.00). The difference in allelic sharing between the two MAAD strata was significant (P < 0.005) and is not likely to be explained by the HLA haplotype, a previously known genetic susceptibility factor for cervical cancer. Our results indicate locus heterogeneity in the susceptibility to cervical cancer between the two strata, with polymorphisms in the 9q32 region mainly showing an effect in women with high MAAD.
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| 19. |
- Engelmark, Malin T., et al.
(author)
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Identification of susceptibility loci for cervical carcinoma by genome scan of affected sib-pairs
- 2006
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 15:22, s. 3351-3360
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Journal article (peer-reviewed)abstract
- Cervical cancer is caused by a combination of environmental and genetic risk factors. Infection by oncogenic types of human papillomavirus is recognized as the major environmental risk factor and epidemiological studies indicate that host genetic factors predispose to disease development. A number of genetic susceptibility factors have been proposed, but with exception of the human leukocyte antigen CHLA, class II, have not shown consistent results among studies. We have performed the first genomewide linkage scan using 278 affected sib-pairs to identify loci involved in susceptibility to cervical cancer. A two-step qualitative non-parametric linkage analysis using 387 microsatellites with an average spacing of 10.5 cM revealed excess allelic sharing at nine regions on eight chromosomes. These regions were further analysed with 125 markers to increase the map density to 1.28 cM. Nominal significant linkage was found for three of the nine loci [9q32 (maximum lod-score, MLS) =1.95, P < 0.002), 12q24 (MLS=1.25, P < 0.015) and 16q24 (MLS=1.35, P < 0.012)]. These three regions have previously been connected to human cancers that share characteristics with cervical carcinoma, such as esophageal cancer and Hodgkin's lymphoma. A number of candidate genes involved in defence against viral infections, immune response and tumour suppression are found in these regions. One such gene is the thymic stromal co-transporter (TSCOT). Analyses of TSCOT single nucleotide polymorphisms further strengthen the linkage to this region (MLS=2.40, P < 0.001). We propose that the 9q32 region contains susceptibility locus for cervical cancer and that TSCOT is a candidate gene potentially involved in the genetic predisposition to this disease.
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| 20. |
- Gustavsson, Inger, et al.
(author)
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Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low grade dysplasia
- 2009
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 45:2, s. 85-89
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human papillomavirus (HPV) testing is an important part of cervical carcinoma screening, and the most widely used assay for detection of HPV is Hybrid Capture 2 (HC2). OBJECTIVES: We compare the HC2 with the real-time PCR hpVIR assay for detection of HPV in follow-up smears of 398 women diagnosed with atypical squamous cells of unknown significance (ASCUS) or low grade cervical intraepithelial neoplasia (CIN 1) in their initial smear. STUDY DESIGN: The two assays target the same set of high-risk (HR) HPVs with exception of HPV68. hpVIR identify individual or groups of HPV types as well as their viral load, while HC2 identify HR HPVs without specification of type. RESULTS: 34% (131/391) of the women were positive with HC2 and 45% (175/391) with hpVIR. 16% (63/391) were positive only with hpVIR and among those with cytology available 6% (3/52) had a CIN 2. The 3% (13/391) of women positive only with HC2 either contained low-risk HPVs or copy numbers below the cut-off for the hpVIR assay. CONCLUSION: The hpVIR assay has a similar sensitivity and specificity as HC2, but hpVIR detect a higher frequency of high-risk HPV infections.
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| 21. |
- Gustavsson, Inger M., et al.
(author)
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Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening
- 2019
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In: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 16:1
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Journal article (peer-reviewed)abstract
- BackgroundThe indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening.MethodsWe performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples.ResultsThe clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons.ConclusionsSamples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.
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| 22. |
- Gustavsson, Inger M., et al.
(author)
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Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.
- 2019
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:1, s. 89-97
-
Journal article (peer-reviewed)abstract
- We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.
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| 23. |
- Gustavsson, Inger M., et al.
(author)
-
Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology
- 2018
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 118:6, s. 896-904
-
Journal article (peer-reviewed)abstract
- Background:This randomised study compared the detection rate of cervical intraepithelial neoplasia-positive (CIN2+) based on histology in women performing repeated self-sampling of vaginal fluid (VF) for human papillomavirus (HPV) test with a control group following the ordinary screening by Pap smear cytology.Methods:36390 women aged 30–49 years scheduled for invitation to organised screening were randomised in two groups, one to perform self-sampling of VF for HPV test (n=17 997, HPV arm) and the other group to perform screening by PAP smear cytology (n=18 393, control arm). HPV positive women in the HPV arm repeated the self-sampling and the HPV test on average 4.4 months later and those with two consecutive positive HPV tests were referred to colposcopy. Outcome was CIN2+ based on histology during 18-month follow-up.Results:Participation rate was 47% in the HPV arm and 39% in the control arm. The HPV prevalence in the first self-sampling was 6.9%, and 71% of these women were HPV positive in their second test. For the per-protocol approach, cumulative prevalence of histological CIN2+ in the HPV arm was 20.2 per 1000 women screened as compared to 10.8 in the control arm. The cumulative prevalence of CIN2+ diagnosed per 1000 years screened was 160.8 in the HPV arm as compared with 25.4 in the control arm.Conclusions:Repeated self-sampling of VF and HPV test had more than a two-fold higher discovery rate of CIN2+ per 1000 women screened as compared with PAP smear cytology.
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| 24. |
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| 25. |
- Gustavsson, Inger, 1965-, et al.
(author)
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Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge
- 2011
-
In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 51:4, s. 255-258
-
Journal article (peer-reviewed)abstract
- BackgroundMost procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media.ObjectivesTo evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA® Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA® Elute Micro card and biopsy analysis.Study designA total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays.ResultAll samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2–3 (CIN 2–3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis.ConclusionThe Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.
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| 26. |
- Gustavsson, Inger, et al.
(author)
-
Use of FTA card for dry collection, transportation and storage of cervical cell specimen to detect high-risk HPV
- 2009
-
In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 46:2, s. 112-116
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The FTA elute micro card, which enable the collection, transport, and archiving of DNA could be an attractive alternative to a liquid based collection system for detection of human papillomavirus (HPV). OBJECTIVES: To develop a method based on the FTA elute micro card for dry collection of cervical epithelial cell samples, suitable for subsequent PCR-based HPV testing. STUDY DESIGN: The method was evaluated by a comparison of the DNA collected by cytobrush and the regular FTA elute micro card from 50 cervical cell samples. The method was then used to estimate the DNA amount in 1040 samples applied to the indicating FTA elute micro card. RESULT: The agreement in HPV positivity between the cytobrush and FTA samples (94%) was excellent (kappa=0.88, 95% CI 0.748-1). All the 1040 samples on the indicating FTA card had sufficient amounts of genomic DNA (>10 copies of a single copy gene) to be suitable for HPV typing. In 53 of the 1040 women the day in the menstrual cycle was noted, and the copy number during follicular phase day 9-13 was found to be statistically significantly lower than for the other three stages in the menstrual cycle (day 4-8, 14, >14) and during menopause. CONCLUSION: The indicating FTA elute micro card represents a suitable medium for collection of cervical cell samples, although follow-up studies are needed to verify the detection of low frequency HPV types.
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| 27. |
- Gustavsson, John, et al.
(author)
-
In-situ activated hydrogen evolution by molybdate addition to neutral and alkaline electrolytes
- 2012
-
In: Journal of Electrochemical Science and Engineering. - : International Association of Physical Chemists (IAPC). - 1847-9286. ; 2:3, s. 105-120
-
Journal article (peer-reviewed)abstract
- Activation of the hydrogen evolution reaction (HER) by in-situ addition of Mo(VI) to the electrolyte has been studied in alkaline and pH neutral electrolytes, the latter with the chlorate process in focus. Catalytic molybdenum containing films formed on the cathodes during polarization were investigated using scanning electron microscopy (SEM), energy-dispersive X ray analysis (EDS), X-ray photoelectron spectroscopy (XPS), and X ray fluorescence (XRF). In-situ addition of Mo(VI) activates the HER on titanium in both alkaline and neutral electrolytes and makes the reaction kinetics independent of the substrate material. Films formed in neutral electrolyte consisted of molybdenum oxides and contained more molybdenum than those formed in alkaline solution. Films formed in neutral electrolyte in the presence of phosphate buffer activated the HER, but were too thin to be detected by EDS. Since molybdenum oxides are generally not stable in strongly alkaline electrolyte, films formed in alkaline electrolyte were thinner and probably co-deposited with iron. A cast iron molybdenum alloy was also investigated with respect to activity for HER. When polished in the same way as iron, the alloy displayed a similar activity for HER as pure iron.
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| 28. |
- Gustavsson, John, 1979-, et al.
(author)
-
In-situ Activated Hydrogen Evolution by Molybdate Addition to Neutral and Alkaline Electrolytes
-
Other publication (other academic/artistic)abstract
- Activation of the hydrogen evolution reaction (HER) by in-situ addition of Mo(VI) to the electrolyte has been studied in alkaline and pH neutral electrolytes, the latter with the chlorate process in focus. Catalytic molybdenum containing films formed on the cathodes during polarization were investigated using scanning electron microscopy (SEM), energy-dispersive X‑ray analysis (EDS), X-ray photoelectron spectroscopy (XPS), and X‑ray fluorescence (XRF). In-situ addition of Mo(VI) activates the HER on titanium in both alkaline and neutral electrolytes and makes the reaction kinetics independent of the substrate material. Films formed in neutral electrolyte consisted of molybdenum oxides and contained more molybdenum than those formed in alkaline solution. Films formed in neutral electrolyte in the presence of phosphate buffer activated the HER, but were too thin to be detected by EDS. Since molybdenum oxides are generally not stable in strongly alkaline electrolyte, films formed in alkaline electrolyte were thinner and probably co-deposited with iron. A cast iron‑molybdenum alloy was also investigated with respect to activity for HER. When polished in the same way as iron, the alloy displayed a similar activity for HER as pure iron.
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| 29. |
- Gyllensten, Ulf, et al.
(author)
-
Primary high-risk HPV screening for cervical cancer in post-menopausal women
- 2012
-
In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 125:2, s. 343-345
-
Journal article (peer-reviewed)abstract
- Objective. The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women. Methods. A cohort of post-menopausal women (n =2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement. Results. High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2 + lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% Cl 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population. Conclusions. Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.
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| 30. |
- Gyllensten, Ulf, et al.
(author)
-
Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer
- 2011
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 105:5, s. 694-697
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling. METHODS: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test. RESULTS: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%). CONCLUSION: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years.
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| 31. |
- Hedlund Lindberg, Julia, et al.
(author)
-
Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid
- 2024
-
In: iScience. - : Cell Press. - 2589-0042. ; 27:2
-
Journal article (peer-reviewed)abstract
- Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence–based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91–1.00) at a specificity of 0.67 (0.40–0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.
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| 32. |
- Hermansson, Ruth S., et al.
(author)
-
Incidence of oncogenic HPV and HPV-related dysplasia five years after a negative HPV test by self-sampling in elderly women
- 2022
-
In: Infectious Agents and Cancer. - : Springer Nature. - 1750-9378. ; 17:42
-
Journal article (peer-reviewed)abstract
- Purpose: Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative.Methods: Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology.Results: Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology.Conclusions: The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.
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| 33. |
- Ivansson, Emma L, et al.
(author)
-
Temporal trends over 3 decades and intrafamilial clustering of HPV types in Swedish patients with cervical cancer in situ
- 2009
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:12, s. 2930-2935
-
Journal article (peer-reviewed)abstract
- Information on HPV type distribution in cervical cancer in situ in different populations is needed for evaluation of prophylactic vaccination programs targeting HPV 16 and 18. In our study, the HPV type prevalence in 1,079 Swedish women from multicase families diagnosed with cervical cancer in situ 1965-1993 was investigated using real-time PCR and archival tissue material. HPV type information was obtained for 974 samples. Among these, HPV 16 (61%) was the dominant type followed by HPV 33/52/58 (24%), HPV 31 (13%) and HPV 18/45 (12%). The detected prevalence of HPV 16 among cancer in situ decreased by 13% over the study period while the group of low frequency high-risk types increased. Related women were not prone to infection by the same type. These data suggest that the prevalence of individual HPV types has changed over time in Swedish patients with cervical cancer in situ. Large-scale studies of pathology biobank materials will enable further insight into the temporal changes of individual HPV types, as baseline information to properly evaluate the effect of vaccine programs. The findings also indicate that genetic susceptibility to cervical cancer operates through general and not type specific susceptibility to HPV infection.
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| 34. |
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| 35. |
- Ivansson, Emma, et al.
(author)
-
Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer
- 2007
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:11, s. 2451-2457
-
Journal article (peer-reviewed)abstract
- Cervical cancer is caused by persistent infection of oncogenichuman papillomavirus (HPV). Most infected women clear the viruswithout developing cervical lesions and it is likely that immunologicalhost factors affect susceptibility to cervical cancer. Theimpact of the human leukocyte antigen (HLA) locus on the risk ofcervical cancer is established and several other genes involved inimmunological pathways have been suggested as biologically plausiblecandidates. The aim of this study was to examine the potentialrole of polymorphisms in 4 candidate genes by analysis of1,306 familial cervical cancer cases and 288 controls. The followinggenes and polymorphisms were studied: Chemokine receptor2 (CCR-2) V64I; Interleukin 4 receptor a (IL-4R) I75V, S503P andQ576R; Interleukin 10 (IL-10) 2592; and Fas ligand (FasL) 2844.The CCR-2 64I variant was associated with decreased risk of cervicalcancer; homozygote carriers of the 64I variant had an oddsratio of 0.31 (0.12–0.77). This association was detected in both carriersand noncarriers of the HLA DQB1*0602 cervical cancer riskallele. The IL-4R 75V variant was associated with increased riskof cervical tumors, cases homozygote for 75V had an odds ratio of1.91 (1.27–2.86) with a tendency that the association was strongerin noncarriers of the DQB1*0602 allele. We did not find any associationfor IL-10 2592, or FasL 2844, previously reported to beassociated with cervical cancer in the Dutch and Chinese populations,respectively.
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| 36. |
- James, Inger, 1953-
(author)
-
Bakom rutinerna : kunskap och omvårdnadspraxis i mänskliga gränssituationer
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis was to study how family members, next of kin, and healthcare professionals construct and use knowledge in nursing praxis in human boundarysituations.The study was carried out on a surgical ward at a university hospital in Sweden.Methodology: Study I: A case study; data concerning a family with six familymembers were collected over 10 months using interviews, conversations, and diary notations.Study II: A hermeneutic approach; interviews with 27 family carers were conductedsix to eight months after a family member’s death. Studies III, IV: a combinedethnographic and hermeneutic approach; participant observations (285 hours), informalconversations (190), and interviews (25) were conducted with 25 nurses and 18 assistant nurses.The main findings were: (I) The family members used beliefs to explain and understandcancer, dying and death. The beliefs were aggregated into eight main beliefs and fourthemes: cancer is a deadly threat/death is a liberator; death can be held at bay/death canbe lived near; dying is done alone/dying should not be done alone; and life has anend/life is endless. These beliefs appear to oscillate between seemingly contrastingpoles. (II) The family carers made their own assessment of their loved one’s conditionand situation. Their actions were characterized by struggling to get treatment, being leftbehind, being partners, keeping the illness at a distance, hovering beside their loved one,waiting for death, and being experts and protectors. The family carers used practicalwisdom, phronesis, regarding what care was the best, or least harmful, for their lovedone in the encounter with professional care. (III) The nurses constructed knowledgethrough greeting the patient, and reading the patient. By being sensitive, using humor,and emotional involvement, understanding was deepened. By being suspicious and selfcritical,interaction was sought with nurse colleagues, the patient, relatives, and the doctor,and additional knowledge was obtained. They strived to be one step ahead in theirefforts to attain an understanding of the patient´s situation. The knowledge nurses makeuse of can be related to the intertwined and embodied forms of theoretical knowledge,i.e., episteme, practical professional knowledge, i.e., techne, and practical wisdom i.e.,phronesis. (IV) The nurses created and used emotional knowing that could be interpretedin relation to various rooms of emotions, thoughts and actions. They strived to dothings correctly in the normative room; created a safe, secure milieu for patients andnext of kin in the safety-security room; and questioned their actions in the critical room.They created an affinity for co-operation that was of benefit in encounters with patientsin the nurses’ affinity room. And they demonstrated compassion for patients and next ofkin; this compassion was particularly evident in the closeness room.Conclusion: In praxis, construction and use of knowledge occurs that often takes placebehind the routines. This knowledge constitutes an important content in nursing. Thehermeneutic spiral can serve a pedagogic purpose in elucidating nursing and its differentforms of knowledge.
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| 37. |
- James, Inger, 1953-, et al.
(author)
-
Emotional knowing in nursing practice : in the encounter between life and death
- 2010
-
In: International Journal of Qualitative Studies on Health and Well-being. - Järfälla, Sweden : Co-Action Publishing. - 1748-2623 .- 1748-2631. ; 5:2
-
Journal article (peer-reviewed)abstract
- Patients, next of kin and nurses in surgical wards often raise existential questions in the encounter between life and death. Nurses' emotional knowing at this encounter is crucial. Consequently, this study's purpose was to analyse and describe nurses' emotional knowing to reveal (a) how this knowing is expressed in daily work and (b) what emotions, thoughts and actions this knowing includes. This study used combined ethnographic and hermeneutic methodologies. Data were collected using participant observations, informal conversations and interviews. We found that nurses' emotional knowing could be interpreted in relation to various rooms of emotions, thoughts and actions. Nurses' judgements formed these rooms. They strived to do things correctly in the normative room; created a safe, secure milieu for patients and next of kin in the safety–security room; and questioned their actions in the critical room. They created affinity for co-operation that benefitted encounters with patients in their affinity room. And they demonstrated sensitivity and compassion to patients and next of kin; sensitivity and compassion were particularly evident in the closeness room. In our main interpretation, we found that nurses' judgements in various rooms (emotional knowing) constitute an expression of practical wisdom (phronesis) in nursing practice.
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| 38. |
- James, Inger, 1953-, et al.
(author)
-
Knowledge constructions in nursing practice : Understanding and integrating different forms of knowledge
- 2010
-
In: Qualitative Health Research. - London : Sage. - 1049-7323 .- 1552-7557. ; 20:11, s. 1500-1518
-
Journal article (peer-reviewed)abstract
- In this combined ethnographic and hermeneutic study we examined which forms of knowledge nurses make use of and how they construct knowledge. We collected data using participant observations, informal conversations, and interviews. Nurses' knowledge construction took the form of a hermeneutic spiral, a journey in which the nurses moved up and down and horizontally, and in which they created understanding. The nurses constructed knowledge from reading the patient's record, the brief oral handover report, greeting the patient, and reading the patient. By being sensitive, using humor, and emotional involvement, they deepened their understanding. By being suspicious and self-critical, they sought interaction with nurse colleagues, the patient, doctor, and relatives, and obtained additional knowledge. They strove throughout the journey to be one step ahead in their efforts to attain an understanding of the patient's situation. We can relate the knowledge nurses make use of to intertwined forms of episteme, techne, and phronesis
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| 39. |
- Johansson Wensman, Jonas, et al.
(author)
-
Markers of Borna disease virus infection in cats with staggering disease
- 2012
-
In: Journal of Feline Medicine and Surgery. - 1098-612X .- 1532-2750. ; 14, s. 573-582
-
Journal article (peer-reviewed)abstract
- Borna disease virus (BDV) is a RNA-virus causing neurological disorders in a wide range of mammals. In cats, BDV infection may cause staggering disease. Presently, staggering disease is a tentative clinical diagnosis, only confirmed at necropsy. In this study, cats with staggering disease were investigated to study markers of BDV infection aiming for improvement of current diagnostics. Nineteen cats fulfilled the inclusion criteria based on neurological signs and pathological findings. In 17/19 cats, BDV infection markers (BDV-specific antibodies and/or BDV-RNA) were found, and antibodies in serum (13/16, 81%) were the most common marker. BDV-RNA was found in 11/19 cats (58%). In a reference population without neurological signs, 4/25 cats were seropositive (16%). The clinical history and neurological signs in combination with presence of BDV infection markers, where serology and rRT-PCR on blood can be helpful tools, improve the diagnostic accuracy in the living cat.
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| 40. |
- Lara Gutiérrez, Ariadna, et al.
(author)
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Identification of Candidate Protein Biomarkers for CIN2+ Lesions from Self-Sampled, Dried Cervico-Vaginal Fluid Using LC-MS/MS
- 2021
-
In: Cancers. - : MDPI. - 2072-6694. ; 13:11
-
Journal article (peer-reviewed)abstract
- Molecular screening programs for cervical cancer detect the presence of human papilloma virus (HPV) in cell material or vaginal fluids. Persistent infection with high-risk HPV is a necessary pre-requisite, but the majority of infections do not lead to pathological states. Additional biomarkers are needed to increase the specificity of the molecular tests. Here, we have investigated the possibility of detecting protein biomarkers using mass spectrometry from dried self-sampled cervico-vaginal fluid deposited on FTA cards. We found significant intra-individual correlations (p < 2.2 × 10-16), although heterogenous protein profiles were obtained between individuals. Out of 3699 proteins found in total, 169 were detected in at least 95% of the samples. Using a discovery/replication design, 18 proteins were found to be significant in the discovery cohort, with higher values in those cases compared to controls. All of these were found to also have higher levels among the cases in the replication cohort, with one protein (DEAD-Box Helicase) remaining statistically significant. Finally, a predictive 7-protein multivariate model was developed with a sensitivity and specificity of 0.90 and 0.55, respectively. Our results demonstrate that robust measurements of protein biomarkers can be obtained from self-sampled dried CVF and that these could be used to predict cervical cancer pre-stages.
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| 41. |
- Lindström, Annika K., 1953-, et al.
(author)
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Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing
- 2018
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: About 30% of the cervical cancer cases in Sweden occur in women older than 60. The primary aim was to evaluate the acceptability of repeated self-sampling at home for HPV-testing in elderly women. The prevalence of HPV and HPV related dysplasia as well as the sensitivity of cytology was evaluated.METHODS: Repeated self-sampling at home for HPV testing was offered 375 women in each of the four age groups 60, 65, 70 and 75 years. Women with two consecutive positive HPV tests were examined with sampling for histology and cytology.FINDINGS: A self-sample was provided by 59.5% (893/1500) of the invited women. The overall prevalence of HPV was 4.4% (95% CI 3.2-6.0, n = 39) in the first test, and 2.5% were persistent positive in the second test (95% C 1.6-3.8, n = 22) collected on average 5.5 months later. Dysplasia, was found in 1.8% (16/893) (95% CI 1.1-3.0) and CIN 2+ in 1.0% (9/893) (95%CI 0.5-2.0) of the women. Of the 16 women with dysplasia in histology, 13 (81.2%) had a normal cytology.INTERPRETATION: Repeated self-sampling at home combined with HPV testing was well accepted among elderly women. A high prevalence of CIN was diagnosed by histology. Cytology showed extremely low sensitivity and should not be recommended for this age group.
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| 42. |
- Marincevic-Zuniga, Yanara, et al.
(author)
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Multiply-primed rolling circle amplification of human papillomavirus using sequence-specific primers
- 2012
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In: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 432:1, s. 57-62
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Journal article (peer-reviewed)abstract
- Multiply-primed rolling circle amplification (RCA) is a suitable technique for amplification of circular templates and has been used to identify novel human papillomaviruses (HPV). In this study we develop an efficient RCA for whole genome amplification of HPV using HPV-specific primers in clinical samples and establish a protocol for whole genome sequencing using the Sanger method. Amplification of cloned HPV-genomes by RCA was compared using specific primers against random hexamers. Using HPV-specific primers increased the effectiveness on average 15.2 times and the enrichment of HPV relative to human gDNA on average 62.2 times, as compared to using random hexamer. RCA products were sequenced without need for cloning, even when using low-input amounts. The technique was successfully used on 4 patient samples from FTA cards, to generate whole HPV-genome sequences. Degenerated HPV-specific primers for RCA produce DNA of sufficient quality and quantity suitable for sequencing and other potential downstream analyses.
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| 43. |
- Mbulawa, Zizipho Z. A., et al.
(author)
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Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women
- 2014
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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 14, s. 51-
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Journal article (peer-reviewed)abstract
- Background: Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities. Methods: Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-time polymerase chain reaction. Results: HIV-positive women had a significantly higher viral load for combined alpha-9 HPV species compared to HIV-negative women (median 3.9 copies per cell compared to 0.63 copies per cell, P = 0.022). This was not observed for individual HPV types. HIV-positive women with CD4 counts > 350/mu l had significantly lower viral loads for alpha-7 HPV species (median 0.12 copies per cell) than HIV-positive women with CD4 = 350/mu l (median 1.52 copies per cell, P = 0.008), but low CD4 count was not significantly associated with increased viral load for other HPV species. High viral loads for alpha-6, alpha-7 and alpha-9 HPV species were significant predictors of abnormal cytology in women. Conclusion: HIV co-infection significantly increased the combined alpha-9 HPV viral load in women but not viral loads for individual HPV types. High HR-HPV viral load was associated with cervical abnormal cytology.
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| 47. |
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| 48. |
- Nordlander, Josefine, et al.
(author)
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Genetic diversity in gooseberry (Ribes uva-crispa), as estimated with SSR markers
- 2022
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In: Scientia Horticulturae. - : Elsevier BV. - 0304-4238 .- 1879-1018. ; 306
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Journal article (peer-reviewed)abstract
- European gooseberry (Ribes uva-crispa L.) is a popular berry crop in many European countries, including Sweden, Denmark and Ukraine. There is no active gooseberry breeding programme in either Sweden or Denmark, but a successful programme is operating in Ukraine. In Sweden and Denmark, research on gooseberries is primarily focused on collection and phenotypic evaluation of genetic resources. As part of these activities, a large number of inventory finds have been collected but have not yet been characterised morphologically or molecularly. The goal of this study was thus to characterise gooseberry germplasm with 15 simple sequence repeat (SSR) markers. From 242 accessions analysed, 153 unique genotypes were identified. Cultivars that have been in widespread cultivation in Sweden, such as the Finnish cultivars ‘Hinnonmäen Keltainen’ and ‘Hinnonmäen Punainen’, had relatively large numbers of synonymous samples. While many inventory finds were identifiable as synonyms of known cultivars, several were found to constitute unique genotypes within the germplasm studied. The studied genotypes clustered relatively well in three posterior groups, consisting of cultivars originating before and after the American gooseberry mildew (Sphaerotheca mors-uvae) outbreak around 1900 and cultivars originating from the territory of the former Soviet Union. A fourth genetic cluster consisting mainly of inventory finds from central and northern Sweden was also identified. In addition, it was possible to verify recorded and stipulated parentages for some of the cultivars studied and to identify three likely parent-parent-child trios. Thus, inventories of local gooseberry germplasm and a subsequent genotyping proved successful in finding unique local genotypes, with potential local adaptation. The data obtained provide a foundation for future studies of gooseberry genetic resources, while also illustrating the importance of a well-curated and phenotypically characterised set of reference cultivars for future studies.
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| 49. |
- Ostensson, Ellinor, et al.
(author)
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Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program
- 2013
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 92:7, s. 830-840
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Journal article (peer-reviewed)abstract
- Background Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear. Objective From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples. Design A cost-effectiveness analysis. Setting The Swedish organized cervical cancer screening program. Methods We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. conventional cytology strategy) and (ii) conventional cytology screening until age 35years, followed by HR-HPV testing using self-collected vaginal samples in women aged 35years (i.e. combination strategy). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies. Main outcome measures Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years. Results Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from Euro43000 to Euro180000 per life-years gained without the cost of added life-years, and from Euro74000 to Euro206000 with costs of added life-years included. Conclusion The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of Euro80000 per life-years gained.
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