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1.
  • Nordén, J., et al. (author)
  • Nutrition impact symptoms and body composition in patients with COPD
  • 2015
  • In: European Journal of Clinical Nutrition. - : Nature Publishing Group. - 0954-3007 .- 1476-5640. ; 69:2, s. 256-261
  • Journal article (peer-reviewed)abstract
    • Background/Objectives:Anorexia or lack of appetite is common in chronic obstructive pulmonary disease (COPD) and may be caused or augmented by several symptoms affecting appetite and eating. We aimed to investigate and quantify the extent of nutrition impact symptoms (NIS) in patients with COPD and to explore relationships between NIS and fat-free mass depletion.Subjects/Methods:The results in this cross-sectional study are based on 169 COPD patients (62% female subjects). Body composition was assessed using bioelectrical impedance spectroscopy and the patients reported NIS by two newly developed questionnaires: the Eating Symptoms Questionnaire (ESQ) and the Disease-Related Appetite Questionnaire (DRAQ).Results:Symptoms with the highest prevalence were dry mouth (71%), stomach ache (39%), pain or aches affecting appetite (36%) and constipation (35%). Problems with diarrhoea and feeling affected by smells were more severe among women compared with men (P<0.05). Thirty-six percent of the patients were depleted (fat-free mass index (FFMI) <15 kg/m(2) for women and FFMI<16 kg/m(2) for men). Depleted patients had more NIS (P<0.05) and also rated appetite and taste of food as worse compared with non-depleted patients (P<0.05).Conclusions:NIS are common in patients with COPD, and depleted patients have more severe symptoms. To investigate how these symptoms are best prevented and/or managed and whether NIS prevention/treatment can affect development of malnutrition in patients with COPD is a challenge for the future.
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2.
  • Arildsen, Nicolai Skovbjerg, et al. (author)
  • Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 1-8
  • Journal article (peer-reviewed)abstract
    • High-grade serous ovarian cancer (HGSOC) is the most common subtype of epithelial ovarian cancer and early detection is challenging. TP53 mutations are a hallmark of HGSOC and detection of these mutations in liquid-based Pap samples could provide a method for early diagnosis. Here we evaluate the use of IBSAFE, an ultra-sensitive droplet digital PCR (ddPCR) method, for detecting TP53 mutations in liquid-based Pap samples collected from fifteen women at the time of diagnosis (diagnostic samples) and/or up to seven years prior to diagnosis (archival samples). We analysed tumours for somatic TP53 mutations with next generation sequencing and were able to detect the corresponding mutations in diagnostic samples from six of eight women, while one patient harboured a germline mutation. We further detected a mutation in an archival sample obtained 20 months prior to the ovarian cancer diagnosis. The custom designed IBSAFE assays detected minor allele frequencies (MAFs) with very high assay sensitivity (MAF = 0.0068%) and were successful despite low DNA abundance (0.17-206.14 ng, median: 17.27 ng). These results provide support for further evaluation of archival liquid-based Pap samples for diagnostic purposes and demonstrate that ultra-sensitive ddPCR should be evaluated for ovarian cancer screening in high-risk groups or in the recurrent setting.
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3.
  • Arroyo Mühr, Laila Sara, et al. (author)
  • Does human papillomavirus-negative condylomata exist?
  • 2015
  • In: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 485, s. 283-288
  • Journal article (peer-reviewed)abstract
    • Condylomata acuminata is caused by human papillomavirus (HPV). PCR with consensus primers will typically detect HPV in >96% of condylomata. Metagenomic sequencing has found that some "HPV-negative" condylomata do indeed contain HPV. We wished to perform a renewed evaluation of the "HPV-negative" condylomata using deeper metagenomics sequencing. Sequencing of whole genome amplified DNA from 40 apparently "HPV-negative" condylomata detected HPV in 37/40 specimens. We found 75 different HPV types, out of which 43 represented novel putative HPV types. Three types were cloned and established as HPV types 200, 201 and 202. Molluscum contagiosum virus was detected in 24 of the 40 samples. In summary, deep sequencing enables detection of HPV in almost all condylomata. "HPV-negative" condylomata might largely be explained by clinical misdiagnosis or the presence of viral variants, distantly related HPV types and/or low viral loads.
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5.
  • Asciutto, Katrin Christine, et al. (author)
  • Follow up with HPV test and cytology as test of cure, 6 months after conization, is reliable
  • 2016
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 95:11, s. 1251-1257
  • Journal article (peer-reviewed)abstract
    • Introduction: Human papillomavirus (HPV) infection is an objective marker with a high sensitivity for finding cervical dysplasia. The objective of the current study is to investigate whether HPV testing, combined with liquid-based cytology, is reliable as a test of cure after the loop electrical excision procedure (LEEP). Material and methods: The LEEP was performed in 330 women for excision of cervical dysplasia. Follow up consisted of HPV testing and liquid-based cytology at six, 12, and 36 months after treatment. Patients with negative co-testing after 6 months were re-examined after 3 years. Patients who tested positive for high-risk HPV and/or dysplasia were followed up 12 months postoperatively. Results: At 6 months, the co-testing was double negative in 169 of 260 tested cases (65%). A positive high-risk HPV test (n = 40) was associated with cytological abnormalities (p < 0.001). After 3 years, 227 of 275 examined cases (83%) co-tested negative, including 154 patients who had already tested negative at 6 months and 37 cases with viral clearance at 12 months. Of 26 patients with high-risk HPV at the 3-year follow up, six had LSIL findings on liquid-based cytology, but neither HSIL lesions nor glandular atypia or cervical cancer was found. A negative high-risk HPV test showed a negative predictive value for HSIL of 100% (95% CI 99.8–100%). Conclusions: Negative co-testing 6 months after LEEP can be considered a reliable test of cure as 3-year follow-up results are consistent with neither HSIL or cancer.
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6.
  • Asciutto, Katrin Christine, et al. (author)
  • Prevalence of high-risk HPV in postmenopausal women with benign cervical cytology - A population-based cohort study
  • 2018
  • In: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:7, s. 4221-4228
  • Journal article (peer-reviewed)abstract
    • Aim: To compare the clinical performance of human papillomavirus (HPV) mRNA and DNA assays in postmenopausal women. Materials and Methods: A total of 5,925 postmenopausal women were tested with cytology and the Luminex HPV DNA assay. High risk-HPV-positive women with benign cytology underwent a complimentary HPV mRNA assay (APTIMA). Both assays and the cytological testing were repeated after 12 months. Results: A total of 334 women were found to be high-risk HPV-positive; 272 out of these women met the inclusion criteria. At follow-up, 25 (9.2%) out of the 272 included women had cytological abnormalities. HPV mRNA assay at follow-up had a sensitivity of 84% (95% confidence interval=63.9-95.4%) and a specificity of 60.2% (95% confidence interval=53.7-66.3%; p=0.0003) to detect these lesions. Corresponding values for the HPV DNA assay were 88% (95% confidence interval=68.8-97.4%) and 43.5% (95% confidence interval=37.2-49.4%). Conclusion: The HPV mRNA assay offers a comparable sensitivity but a higher specificity than the HPV DNA assay in detecting precancerous cervical lesions.
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7.
  • Asciutto, Katrin Christine, et al. (author)
  • Self-sampling with HPV mRNA analyses from vagina and urine compared with cervical samples
  • 2018
  • In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 101, s. 69-73
  • Journal article (peer-reviewed)abstract
    • Background: In order to increase coverage in the organized cervical screening program, self-sampling with HPV analyses has been suggested. Objectives: The aim was to compare human papillomavirus (HPV) mRNA detection in vaginal and urine self-collected samples with clinician-taken cervical samples and the corresponding clinician-taken histological specimens. Study design: Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 209 women with the Aptima mRNA assay (Hologic Inc, MA, USA). Cervical cytology, colposcopy, biopsy and/or the loop electrosurgical excision procedure (LEEP) were performed in every examination. Results: The sensitivity of the HPV mRNA test in detecting high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer cases was as follows: for the vaginal self-samples 85.5% (95% CI; 75.0–92.8), the urinary samples 44.8% (95% CI; 32.6–57.4), and for routine cytology 81.7% (95% CI; 70.7–89.9). For the clinician-taken cervical HPV samples the sensitivity of the HPV mRNA test in detecting HSIL/AIS/cancer was 100.0% (95% CI; 94.9–100.0). The specificity of the HPV mRNA was similar for the clinician-taken cervical HPV samples and the self-samples: 49.0% vs. 48.1%. The urinary HPV samples had a specificity of 61.9% and cytology had a specificity of 93.3%. Conclusion: The sensitivity of the Aptima HPV mRNA test in detecting HSIL/AIS/cancer from vaginal self-samples was similar to that of routine cytology. The Aptima HPV mRNA vaginal self-sampling analysis may serve as a complement in screening programs.
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8.
  • Borgfeldt, Christer, et al. (author)
  • Increased HPV detection by the use of a pre-heating step on vaginal self-samples analysed by Aptima HPV assay
  • 2019
  • In: Journal of Virological Methods. - : Elsevier BV. - 0166-0934. ; 270, s. 18-20
  • Journal article (peer-reviewed)abstract
    • Background: We recently reported a sensitivity of 85.5% to detect high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer by the use of self-collected vaginal samples analysed by the Aptima mRNA HPV assay (AHPV). Objectives: To increase detection of HPV among self-samples. Study design: We used a pre-heating step at 90 °C for 1 h on our previously AHPV-negative self-samples (N = 20) among women with AHPV-positive cervical samples. We also analysed AHPV results before and after the heating among a series of self-samples from women who had not attended cervical screening for > 7 years (N = 173). Results: After heating, 55% (11/20) of the self-samples became AHPV-positive. By updating our original series 93.1% (121/130, 95% CI: 87.3–96.8) of the self-samples were AHPV-positive among women with AHPV-positive cervical samples, and among women with histologically confirmed cervical intraepithelial neoplasia or worse (CIN2+) now 95.3% (61/64, 95% CI: 86.9–99.0) of the self-samples were AHPV-positive. Among the 11 AHPV-positive self-samples we detected high-risk HPV types in 10 of the samples (HPV16 3 cases, HPV18 1, HPV31 1, HPV33 1, HPV 45 1, HPV51 2, HPV 56 and 58 1, HPV42 and 90 1 [low risk]) by multiplex PCR and Luminex assay. Among the self-samples from the non-attenders 16% (27/170) and 5.3% (8/152) were AHPV-positive after and before the heating step, respectively (P = 0.0022). Concerning validity of AHPV-results, 99% (170/172) were valid after the heating step compared to 88% (152/172) before the heating step (P < 0.0001). Conclusions: A pre-heating step on vaginal self-samples increased HPV detection by the AHPV assay.
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9.
  • Eklund, Carina, et al. (author)
  • Continuing global improvement in human papillomavirus DNA genotyping services : The 2013 and 2014 HPV LabNet international proficiency studies
  • 2018
  • In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 101, s. 74-85
  • Journal article (peer-reviewed)abstract
    • Background: Accurate and internationally comparable human papillomavirus (HPV) DNA detection and typing services are essential for HPV vaccine research and surveillance. Objectives: This study assessed the proficiency of different HPV typing services offered routinely in laboratories worldwide. Study design: The HPV Laboratory Network (LabNet) has designed international proficiency panels that can be regularly issued. The HPV genotyping proficiency panels of 2013 and 2014 contained 43 and 41 coded samples, respectively, composed of purified plasmids of sixteen HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68a and 68b) and 3 extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 International Units of HPV 16 and HPV 18 and 500 genome equivalents for the other 14 HPV types, with at least 97% specificity. Results: Ninety-six laboratories submitted 136 datasets in 2013 and 121 laboratories submitted 148 datasets in 2014. Thirty-four different HPV genotyping assays were used, notably Linear Array, HPV Direct Flow-chip, GenoFlow HPV array, Anyplex HPV 28, Inno-LiPa, and PGMY-CHUV assays. A trend towards increased sensitivity and specificity was observed. In 2013, 59 data sets (44%) were 100% proficient compared to 86 data sets (59%) in 2014. This is a definite improvement compared to the first proficiency panel, issued in 2008, when only 19 data sets (26%) were fully proficient. Conclusion: The regularly issued global proficiency program has documented an ongoing worldwide improvement in comparability and reliability of HPV genotyping services.
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10.
  • Ernstson, Avalon, et al. (author)
  • Detection of HPV mRNA in Self-collected Vaginal Samples Among Women at 69-70 Years of Age
  • 2019
  • In: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 39:1, s. 381-386
  • Journal article (peer-reviewed)abstract
    • BACKGROUND/AIM: Cervical cancer is associated with poorer diagnosis among the elderly and pap-smear screening has a lower sensitivity. Self-sampling for detection of high-risk human papillomavirus (hr-HPV) may be an alternative screening method. The aim of this study was to analyze the response rate to vaginal HPV self-sampling and the HPV mRNA prevalence among women 69-70 years. MATERIALS AND METHODS: An HPV self-sampling kit was sent to 1,000 women 69-70 years whom had not taken a cervical smear in ≥5 years. The samples were analyzed by the Aptima HPV mRNA assay. HPV-positive women were recalled for a follow-up examination. RESULTS: The self-sample response rate was 43.3%. The HPV mRNA prevalence was 6.2%. All HPV-positive women attended follow-up. CONCLUSION: HPV self-sampling was accepted among older women. Although the HPV mRNA prevalence was 6.2%, no high-grade cytological abnormalities were found. Larger studies are needed to elucidate hr-HPV self-sampling as a tool to identify older women at risk of cervical cancer.
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11.
  • Faust, Helena, et al. (author)
  • Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines.
  • 2016
  • In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; , s. 1559-1559
  • Journal article (peer-reviewed)abstract
    • Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil™) or bivalent (Cervarix™) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix™, all subjects became seropositive for HPV16 and 18. After Gardasil™ vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were <1 international unit (IU) in 87% of study subjects before vaccination but >10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil™ vaccination for >50% of vaccinated females for HPV 31, 35 and 73 and for >50% of Cervarix™-vaccinated females for HPV 31, 33, 35, 45, 56 and 58. Cross-reactivity with non-genital HPV types was also detected. In conclusion, HIV-infected subjects responded to HPV vaccination with induction of neutralizing antibodies against both vaccine and non-vaccine types.
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12.
  • Faust, Helena, et al. (author)
  • Prevalence of human papillomavirus types, viral load and physical status of HPV16 in head and neck squamous cell carcinoma from the South Swedish Health Care Region
  • 2016
  • In: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97:11, s. 2949-2956
  • Journal article (peer-reviewed)abstract
    • Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74% of the HPV-positive cases. HPV was detected in 65% (92/141) and 11% (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73% (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003–1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100% (17/17) and 68% (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy Cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6%, whereas entirely episomal and mixed virus was detected in 51 and 42% of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48%), the episomal HPV16 is salient (93%) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.
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13.
  • Forslund, Anders, 1982, et al. (author)
  • Bridging the gap between point cloud and CAD: A method to assess form error in aero structures
  • 2016
  • In: 18th AIAA Non-Deterministic Approaches Conference, 2016; San Diego; United States; 4 January 2016 through 8 January 2016. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103971
  • Conference paper (peer-reviewed)abstract
    • One barrier to the successful implementation of probabilistic design methods is the lack of methods for characterizing form error. Form error, defined as the irregular deviations in geometry, is hard to describe in a virtual environment. This paper showcases a method that uses a simulation platform to assess the effects of form error on the aerodynamic, thermal and structural performance of an aero structure. Particularly, it looks at how bridging the gap between nominal CAD-geometries and point-cloud-based scanned geometries, creates a unified model where physical geometrical deviations can be isolated from model uncertainties. In a sample fatigue life problem, the effects of geometrically deviated parts is assessed. Further, a permutation genetic algorithm is implemented to optimize deviated part configuration. From a research standpoint, the showcased method contributes to addressing the genesis problem inherent in uncertainty quantification. From and industrial point of view, this method provides a precise, cost-effective tool for dealing with effects variations, which in turn increases both product quality and development process efficiency.
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14.
  • Forslund, Anders, 1982, et al. (author)
  • Designing simulation platforms for uncertainty—An example from an aerospace supplier
  • 2015
  • In: 17th AIAA Non-Deterministic Approaches Conference. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103476 ; , s. 9-
  • Conference paper (peer-reviewed)abstract
    • Variation poses a serious threat to the functionality, safety and reliability of aircraft. As the aerospace industry depends ever more heavily on modeling and simulation in their product development, there is an increased need to assess the effects of variation in a virtual environment. This paper outlines the methods proposed by a Swedish aerospace supplier to incorporate robust design methodology into platform-based product development. These methods evaluate how geometric variation affects the aerodynamic, thermal and structural performance of turbofan engine components. The results of the study show that simulation results are heavily affected by variations in geometry. Moreover, this study showcases automated simulation platforms as a powerful tool for robustness analyses. In addition to optimizing the robustness of products, these tools are equally effective as a tool for allocating engineering resources to optimize quality-to-cost ratio. © 2015 American Institute of Aeronautics and Astronautics Inc. All rights reserved.
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15.
  • Forslund, Anders, 1982, et al. (author)
  • Evaluating How Functional Performance in Aerospace Components Is Affected by Geometric Variation
  • 2018
  • In: SAE International Journal of Aerospace. - : SAE International. - 1946-3855 .- 1946-3901. ; 11:1, s. 5-26
  • Journal article (peer-reviewed)abstract
    • Geometric variation stemming from manufacturing can be a limiting factor for the quality and reliability of products. Therefore, manufacturing assessments are increasingly being performed during the early stages of product development. In the aerospace industry, products are complex engineering systems, the development of which require multidisciplinary expertise. In such contexts, there are significant barriers against assessing the effects of geometric variation on the functionality of products. To overcome these barriers, this article introduces a new methodology consisting of a modelling approach linked to a multidisciplinary simulation environment. The modelling approach is based on the parametric point method, which allows point-scanned data to be transferred to parameterised CAD models. In a case study, the methodology is implemented in an industrial setting. The capability of the methodology is demonstrated through a few applications, in which the effects of geometric variation on the aerodynamic, thermal, and structural performance of a load-bearing turbofan component are analysed. The proposed methodology overcomes many of the current barriers, making it more feasible to assess the effects of geometric variation during the early design phases. Despite some limitations, the methodology contributes to an academic understanding of how to evaluate geometric variation in multidisciplinary simulations and provides a tool for industry.
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16.
  • Forslund, Ola, et al. (author)
  • A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
  • 2019
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development. Methods: Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed. Results: After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab. Conclusions: We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development.
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17.
  • Forslund, Ola, et al. (author)
  • HPV-mRNA and HPV-DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri
  • 2019
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:5, s. 1073-1081
  • Journal article (peer-reviewed)abstract
    • Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at −80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5–7 years later were comparable [76.3% (95% CI: 65.8%–84.3%) and 82.5% (95% CI: 72.6%–89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95–99.98) and 99.98% (95% CI: 99.96–99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.
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18.
  • Forslund, Ola Kenji, et al. (author)
  • Magnetic phase diagram of K 2 Cr 8 O 16 clarified by high-pressure muon spin spectroscopy
  • 2019
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
  • Journal article (peer-reviewed)abstract
    • The K 2 Cr 8 O 16 compound belongs to a series of quasi-1D compounds with intriguing magnetic properties that are stabilized through a high-pressure synthesis technique. In this study, a muon spin rotation, relaxation and resonance (μ + SR) technique is used to investigate the pressure dependent magnetic properties up to 25 kbar. μ + SR allows for measurements in true zero applied field and hereby access the true intrinsic material properties. As a result, a refined temperature/pressure phase diagram is presented revealing a novel low temperature/high pressure (p C1 = 21 kbar) transition from a ferromagnetic insulating to a high-pressure antiferromagnetic insulator. Finally, the current study also indicates the possible presence of a quantum critical point at p C2 ~ 33 kbar where the magnetic order in K 2 Cr 8 O 16 is expected to be fully suppressed even at T = 0 K.
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19.
  • Forslund, Ola Kenji, et al. (author)
  • Magnetic phase diagram of K2Cr8O16 clarified by high-pressure muon spin spectroscopy
  • 2019
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • The K2Cr8O16 compound belongs to a series of quasi-1D compounds with intriguing magnetic properties that are stabilized through a high-pressure synthesis technique. In this study, a muon spin rotation, relaxation and resonance (mu+SR) technique is used to investigate the pressure dependent magnetic properties up to 25 kbar. mu+SR allows for measurements in true zero applied field and hereby access the true intrinsic material properties. As a result, a refined temperature/pressure phase diagram is presented revealing a novel low temperature/high pressure (p(C1) = 21 kbar) transition from a ferromagnetic insulating to a high-pressure antiferromagnetic insulator. Finally, the current study also indicates the possible presence of a quantum critical point at p(C2) similar to 33 kbar where the magnetic order in K2Cr8O16 is expected to be fully suppressed even at T = 0 K.
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20.
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21.
  • Forslund, Ola Kenji (author)
  • Your Muonium is μ-drogen
  • 2018
  • In: Journal of the Physical Society of Japan. - : Journal of the Physical Society of Japan. - 0031-9015 .- 1347-4073.
  • Journal article (peer-reviewed)
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22.
  • Forslund, Ola Kenji, et al. (author)
  • μ+SR Study of K2Cr8O16 Under Hydrostatic Pressure
  • 2018
  • In: Journal of the Physical Society of Japan. - : Physical Society of Japan. - 0031-9015 .- 1347-4073.
  • Journal article (peer-reviewed)abstract
    • In this study, the magnetic ground state of the hollandite type material K2Cr8O16 was tuned by externally applied pressure and investigated using µ+SR method in Zero-field (ZF) and weak-transversefield (wTF) configurations. As a result, the obtained magnetic transition temperature for the measuredpressures differs notably from magnetization measurements. Moreover, both wTF and ZF data reveala transition between two different magnetically ordered states at low temperatures for higher pressures. Further theoretical and experimental studies are currently being planned in order to elucidatethe detailed nature of the magnetically ordered phase. 
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23.
  • Forslund, Ola, et al. (author)
  • Mycoplasma genitalium and macrolide resistance-associated mutations in the Skåne Region of Southern Sweden 2015
  • 2017
  • In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 97:10, s. 1235-1238
  • Journal article (peer-reviewed)abstract
    • Mycoplasma genitalium is a sexually transmitted infection ordinarily treated with azithromycin. Emerging resistance to macrolide is linked to mutations in the 23S rRNA gene. We analysed the frequency of such mutations of M. genitalium isolates from patients that were symptomatic, and from sexual partners of symptomatic individuals, from October to December of 2015, in the Skåne Region of Sweden. Mutations were analysed by the use of DNA sequencing. Overall, 11.9% (145/1,311) and 17.0% (116/704) of females and males were positive for M. genitalium, respectively. Macrolide resistant mutations were detected in 13% (31/239) of M. genitalium isolates from first-test patient samples. Twenty-one (8.8%) and 10 (4.2%) of the isolates had point mutations of the 23S-gene at position 2072 and 2071, respectively. Two different M. genitalium isolates were detected simultaneously in two cases. In summary, we found a relatively low rate of macrolide-resistant M. genitalium in the region of Southern Sweden.
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24.
  • Forslund, Ola, et al. (author)
  • Viral load and mRNA expression of HPV type 6 among cases with recurrent respiratory papillomatosis
  • 2016
  • In: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 126:1, s. 122-127
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES/HYPOTHESIS: To determine viral load of human papillomavirus type 6 (HPV6), physical state of HPV6-DNA, and transcription level of HPV6 E7-mRNA in laryngeal papilloma and in adjacent healthy mucosa.STUDY DESIGN: Case series.METHODS: A papilloma biopsy was collected from each of 25 adult patients with respiratory recurrent papillomatosis. From 14 of the 25 patients, we first collected a biopsy from healthy mucosa of the false vocal fold and another from the papilloma. Quantity of HPV6 and E7-mRNA was measured by polymerase chain reaction.RESULTS: For the papilloma, the median load of HPV6 was 41 copies/cell, and the lowest amount was 5.4 copies/cell. Human papillomavirus type 6 was detected in 50% (7/14) of the healthy mucosa, with a median of 1.1 copies/cell, and the highest amount was 6.6 copies/cell. Overall, viral load was higher in papilloma than in healthy mucosa (P < 0.05). The average HPV6 E2/E7-DNA ratio was 1.3, indicating an episomal state. Human papillomavirus type 6-mRNA was detected in all HPV6-DNA-positive samples. The transcription median ratio of HPV6-mRNA/HPV6-DNA was 1.5 in papilloma and 3.8 in healthy mucosa.CONCLUSION: The amount of HPV6-DNA was consistently higher in the papilloma than in healthy mucosa. The transcription level of HPV6 E7 mRNA was similar in the papilloma and in normal mucosa. We suggest that interfering with replication of HPV6 and suppression of HPV6 to fewer than five copies/cell may be curative.LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:122-127, 2016.
  •  
25.
  • Holm, Anna, et al. (author)
  • Kirurgi vid respiratoriska papillom kräver god ventilation : personalen måste skyddas mot HPV-smitta – högfrekvent jetventilationsteknik kan ge bättre operationsresultat
  • 2016
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 113:41
  • Journal article (peer-reviewed)abstract
    • We describe a non-smoking patient with juvenile onset recurrent respiratory papillomatosis (RRP), genotyped as human papilloma virus (HPV)11. The patient has undergone a total of 133 surgical CO2 laser sessions, whereof the last 28 using a high frequency jet ventilation technique (HFJV). Since completed vaccination (Gardasil) in February 2013, the patient underwent one surgery in September 2013 and was considered being in remission. In March 2015, the patient was diagnosed with a left-sided lung cancer, genotyped as HPV11, a HPV subtype associated with a more aggressive disease with higher morbidity and mortality. We advocate that RRP patients should be ventilated with HFJV technique in order to enhance surgical radicality. Furthermore, the operation should be performed in operating theaters with high air exchange/minute, optimized local exhaust ventilation, and specific masks to ensure safe conditions for patients and staff.
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26.
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27.
  • Horio, M., et al. (author)
  • Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates
  • 2018
  • In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:7
  • Journal article (peer-reviewed)abstract
    • We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k(z) dispersion is observed along the nodal direction, whereas a significant antinodal k(z) dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La2-xSrxCuO4 cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.
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28.
  • Jana, Somnath, et al. (author)
  • Revisiting Goodenough-Kanamori rules in a new series of double perovskites LaSr1-xCaxNiReO6
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
  • Journal article (peer-reviewed)abstract
    • The magnetic ground states in highly ordered double perovskites LaSr1-xCaxNiReO6 (x = 0.0, 0.5, 1.0) are studied in view of the Goodenough-Kanamori rules of superexchange interactions in this paper. In LaSrNiReO6, Ni and Re sublattices are found to exhibit curious magnetic states separately, but no long range magnetic ordering is achieved. The magnetic transition at similar to 255 K is identified with the independent Re sublattice magnetic ordering. Interestingly, the sublattice interactions are tuned by modifying the Ni-O-Re bond angles through Ca doping. Upon Ca doping, the Ni and Re sublattices start to display a ferrimagnetically ordered state at low temperature. The neutron powder diffraction data reveals long range ferrimagnetic ordering of the Ni and Re magnetic sublattices along the crystallographic b-axis. The transition temperature of the ferrimagnetic phase increases monotonically with increasing Ca concentration.
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29.
  • Johansson, Hanna K, et al. (author)
  • Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.
  • 2015
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
  • Journal article (peer-reviewed)abstract
    • Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology.
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30.
  • Kobayashi, Shintaro, et al. (author)
  • Linear Trimer Formation with Antiferromagnetic Ordering in 1 T-CrSe2 Originating from Peierls-like Instabilities and Interlayer Se-Se Interactions
  • 2019
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 58:21, s. 14304-14315
  • Journal article (peer-reviewed)abstract
    • Anomalous successive structural transitions in layered 1T-CrSe 2 with an unusual Cr 4+ valency were investigated by synchrotron X-ray diffraction. 1T-CrSe 2 exhibits dramatic structural changes in in-plane Cr-Cr and interlayer Se-Se distances, which originate from two interactions: (i) in-plane Cr-Cr interactions derived from Peierls-like trimerization instabilities on the orbitally assisted one-dimensional chains and (ii) interlayer Se-Se interactions through p-p hybridization. As a result, 1T-CrSe 2 has the unexpected ground state of an antiferromagnetic metal with multiple Cr linear trimers with three-center-two-electron σ bonds. Interestingly, partial substitution of Se for S atoms in 1T-CrSe 2 changes the ground state from an antiferromagnetic metal to an insulator without long-range magnetic ordering, which is due to the weakening of interlayer interactions between anions. The unique low-temperature structures and electronic states of this system are determined by the competition and cooperation of in-plane Cr-Cr and interlayer Se-Se interactions.
  •  
31.
  • Kocjan, Boštjan J, et al. (author)
  • Molecular methods for identification and characterization of novel papillomaviruses.
  • 2015
  • In: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 21:9, s. 808-816
  • Research review (peer-reviewed)abstract
    • Papillomaviruses (PV) are a remarkably heterogeneous family of small DNA viruses that infect a wide variety of vertebrate species and are etiologically linked with the development of various neoplastic changes of the skin and mucosal epithelia. Based on nucleotide similarity, PVs are hierarchically classified into genera, species and types. Novel human PV (HPV) types are given a unique number only after the whole genome has been cloned and deposited with the International HPV Reference Center. As of March 09, 2015, 200 different HPV types, belonging to 49 species, had been recognized by the International HPV Reference Center. In addition, 131 animal PV types identified from 66 different animal species exist. Recent advances in molecular techniques have resulted in an explosive increase in the identification of novel HPV types and novel subgenomic HPV sequences in the last few years. Among PV genera, the Gamma-PV genus has been growing most rapidly in recent years with 80 completely sequenced HPV types, followed by Alpha- and Beta-PV genera that have 65 and 51 recognized HPV types, respectively. We reviewed in detail the contemporary molecular methods most often used for identification and characterization of novel PV types, including polymerase chain reaction, rolling circle amplification and next generation sequencing. Furthermore, we present a short overview of 12 and 10 novel HPV types recently identified in Sweden and Slovenia, respectively. Finally, an update on the International Human Papillomavirus Reference Center is provided.
  •  
32.
  • Kofoed, Kristian, et al. (author)
  • Low Prevalence of Oral and Nasal Human Papillomavirus in Employees Performing CO2-laser Evaporation of Genital Warts or Loop Electrode Excision Procedure of Cervical Dysplasia
  • 2015
  • In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 95:2, s. 173-176
  • Journal article (peer-reviewed)abstract
    • Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV-related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p=0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0% P=0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.
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33.
  • Kristiansen, Sinja, et al. (author)
  • Risk Factors for Penile Intraepithelial Neoplasia : A Population-based Register Study in Sweden, 2000-2012
  • 2019
  • In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 99:3, s. 315-320
  • Journal article (peer-reviewed)abstract
    • Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.
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34.
  • Lee, Jun Han, et al. (author)
  • TPL2 is an oncogenic driver in keratocanthoma and squamous cell carcinoma
  • 2016
  • In: Cancer Research. - 0008-5472. ; 76:22, s. 6712-6722
  • Journal article (peer-reviewed)abstract
    • Squamous cell carcinoma (SCC) and keratoacanthoma (KA; SCC/KA) research has been hampered mainly by our lack of understanding the underlying genetic and epigenetic alterations associated with SCC/KA development, as well as the lack of animal models that faithfully recapitulate histopathologic features of human SCC/KA. Here, we show that TPL2 over-expression induced both cell transformation in immortalized human keratinocytes and SCC and KA-like cutaneous SCC (cSCC) development in mice. Mechanistically, activation of TPL2 downstream signaling pathways such as MEK/ERK MAPK, mTOR, NF-κB, and p38 MAPK leads to TPL2-mediated cell transformation in immortalized human keratinocytes and tumorigenesis in mice. Most importantly, TPL2 overexpression is required for iTPL2 TG-driven SCC and KA-like cSCC tumor maintenance, validating TPL2 as a possible drug target for the treatment of SCC/KA. Finally, we verified that TPL2 is over-expressed in human cutaneous metastatic SCC and KA clinical specimens compared with normal skin. Taken together, our results establish TPL2 as an oncogenic driver in SCC/KA development.
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35.
  • Letsolo, Boitelo T, et al. (author)
  • Establishment and characterization of a human papillomavirus type 16-positive tonsillar carcinoma xenograft in BALB/c nude mice
  • 2016
  • In: Head and Neck. - : Wiley. - 1043-3074. ; 38:3, s. 25-417
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Among head and neck cancers, human papillomavirus type 16 (HPV16) is associated with tonsillar carcinomas. Despite this, no HPV16-positive tonsillar cancer cell line has been established in nude mice.METHODS: Fresh tonsillar carcinoma biopsies were obtained from 23 patients and implanted subcutaneously into nude mice (BALB/c, nu/nu).RESULTS: After 7 months, one xenograft was established. The primary tumor harbored 2.7 copies (95% confidence interval = 2.4-2.9) of HPV16/cell and displayed 99.9% (7904/7906) nucleotide identity to HPV16 (EU118173.1). The xenograft showed increased methylation in two E2-binding sites of the HPV16 genome. Both episomal and integrated HPV16 were detected in the original tumor and in 14 xenografts from the second passage. From this passage, a viral load of 6.4 copies/cell (range = 4.6-9.6) and 3.7 (range = 1.0-5.5) E7-mRNA transcripts/HPV16-genome were detected.CONCLUSION: This xenograft represents the first established HPV16-positive tonsillar tumor in nude mice and could provide an experimental system of HPV16-positive tonsillar cancers. © 2015 Wiley Periodicals, Inc. Head Neck 38: 417-425, 2016.
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36.
  • Lindroth, Ylva, et al. (author)
  • Population-based primary HPV mRNA cervical screening compared with cytology screening
  • 2019
  • In: Preventive Medicine. - : Elsevier BV. - 0091-7435. ; 124, s. 61-66
  • Journal article (peer-reviewed)abstract
    • Primary HPV screening for cervical cancer by HPV mRNA testing (Aptima)was implemented in January 2017, for women ≥30 through 70 years, in the Region of Skåne, Sweden. HPV positive samples underwent cytology assessment, and women with any degree of abnormal cytology were referred for colposcopy. The aim was to audit the primary HPV screening program, by comparing the cytology results to those of corresponding women (aged ≥30 through 65 years)screened with conventional cytology during 2016. Overall, HPV was detected among 7.0% (4433/63,055)of the women ≥30–70 years in the primary HPV screening program. Among a co-tested (cytology and HPV)subgroup aged 40–42 years (N = 5039), HPV was detected in 100% (28/28)of high-grade squamous intraepithelial lesions (HSIL)and atypical squamous cells of undetermined significance (ASCUS)where HSIL could not be excluded (ASC[sbnd]H)(9/9), and in 80% (4/5)of cases of atypical glandular cells (AGC). Among women ≥30–65 years, the proportion ASCUS or worse (ASCUS+)was similar with cytology (3.52% [2016])and primary HPV screening (3.70% [2017]). Only the proportion of ASC-H changed by the use of primary HPV screening, from 0.13% (2016)to 0.23% (2017)(p < 0.001). The colposcopy referral rate increased by 54% (3.70 vs 2.41%), when primary HPV screening was introduced. In conclusion, the implemented primary HPV screening approach demonstrated similar prevalence of ASCUS+ cytology as conventional screening. In addition, primary HPV screening decreased cytology assessments by 86% in our screening population of women 30 through 70 years taken into account the co-tested women.
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37.
  • Lindroth, Ylva, et al. (author)
  • Spectrum of HPV types before and after treatment of cervical intraepithelial neoplasia grade 2 and 3
  • 2017
  • In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 97, s. 38-43
  • Journal article (peer-reviewed)abstract
    • Background To monitor residual disease after treatment of high grade cervical intraepithelial neoplasia (CIN), cytology together with human papillomavirus (HPV) testing are commonly performed. Objectives To analyse the spectrum of HPV types before and after treatment. Study design This register-based study included 446 women treated for CIN2 or 3, where cytology samples had been HPV-tested before and after treatment by the use of the MGP-PCR Luminex HPV L1-DNA-assay identifying 39 HPV types, including 12 high risk (HR) HPV types. Results Before and after treatment, 706 and 248 HPV isolates were detected of 36 and 34 different HPV types, respectively. Among all the HR HPV isolates, type-specific persistency was observed among 14% (76/542) after treatment, compared to 34% (31/92) of low-risk (LR) HPV isolates (p < 0.001). Among the potential high risk (PHR) HPV isolates, 8.3% (6/72) persisted. Totally, 99% (440/446) and 40% (179/446) of the women were HPV-positive before and after treatment, respectively. At least one of the 12 HR HPV types was present in 91% (404/446) and 24% (109/446) of the women before and after treatment, respectively (p < 0.0001). HR HPV types were present both before and after treatment among 23% (102/446) of the women, and 16% (71/446) manifested at least one persistent HR HPV type. The sensitivity, specificity and negative predictive value of HR HPV testing for detection of residual high grade squamous intraepithelial lesion (HSIL) was based on the first cytology after treatment, and was 91.7% (95% CI: 61.5%–99.8%), 84.1% (95% CI: 80.0%–87.7%) and 99.7% (95% CI: 98.2%–100.0%), respectively. Conclusions About one out six treated women (16%) manifested at least one persistent HR HPV type, that was associated with recurrent or residual HSIL disease (odds ratio 58.1, 95% CI 7.4–457) (p = 0.0001). Testing for HR HPV demonstrated high sensitivity (92%) for residual HSIL. The higher persistency rate of LR HPV types suggests that they are more likely to be outside the treated area.
  •  
38.
  • Muhr, L. Sara Arroyo, et al. (author)
  • Human papillomavirus type 197 is commonly present in skin tumors
  • 2015
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:11, s. 2546-2555
  • Journal article (peer-reviewed)abstract
    • Non-melanoma skin cancers commonly contain Human Papillomavirus (HPV), but the types found have varied depending on the polymerase chain reaction (PCR) primer systems used. Whole genome amplified DNA (not amplified by any specific PCR primers) from 91 skin lesions [41 squamous cell skin carcinomas (SCCs), 8 keratoacanthomas, 22 actinic keratoses, 3 basal cell carcinomas and 17 SCCs in situ] were sequenced. All samples were sequenced both at 160 Mb and 1.8 Gb sequencing depth per sample. The sequences from 10 different HPVs in 47/91 specimens were found. Sequences represented four established HPV types (HPV types 16, 22, 120, 124), two previously known putative types (present in GenBank) and four previously unknown HPV sequences (new putative types). The most commonly detected virus was cloned, sequenced and designated as HPV197. Type-specific real-time PCR detected HPV197 in 34/91 specimens. For comparison, a pool of the same samples after general primer PCR amplification was also sequenced. This revealed 40 different HPVs, but only two HPV types were detected both with sequencing without prior PCR and with sequencing PCR amplicons, suggesting that sequencing without prior PCR gives a more unbiased representation of the HPVs present. In summary, it was found that HPV can be sequenced from most skin disease specimens and HPV197 appeared to be the most commonly present virus. What's new? Some skin cancers such as squamous cell carcinomas occur more often in immune compromised individuals, pointing to an infectious agent as cause. In an unbiased approach the authors used next-generation sequencing to examine 91 non-melanoma skin cancer lesions. Most skin lesions contained Human Papilloma Virus (HPV). The authors cloned and sequenced a new type, HPV type 197, present in 34 of the 91 skin lesions. HPV197 has only 75% similarity with the most closely related known HPV (HPV178), suggesting a possible new agent involved in the carcinogenesis of non-melanoma skin lesions.
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39.
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40.
  • Nilsson, Johan S., et al. (author)
  • Intralesional EBV-DNA load as marker of prognosis for nasopharyngeal cancer
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • Nasopharyngeal cancer (NPC) is associated with the Epstein-Barr virus (EBV). The clinical presentation and prognosis of NPC is well described, but not in relation to intralesional EBV-DNA load. In a retrospective design, 48 patients with NPC were examined. Patient history was re-evaluated, and diagnostic biopsies were re-examined. Furthermore, intralesional EBV-DNA was quantitated and HPV status determined. Cancer stage, disease-free survival (DFS), and overall survival (OS) were assessed. Of the 48 patients, 36 (75%) patients featured lesions that were positive for EBER (Epstein–Barr virus-encoded small RNA) and 40 (83%) were positive for EBV-DNA. Seven patients (15%) were HPV positive. The levels of EBV-DNA ranged from 0.0005 to 94617 copies/cell. An EBV-DNA load of more than 70 copies/cell was associated with a prolonged DFS for EBV-DNA positive patients treated with curative intent (p = 0.046). In conclusion, the EBV-DNA load in NPC lesions appears to vary greatly. For patients with EBV-DNA positive NPC treated with curative intent, an EBV-DNA load of more than 70 copies/cell is associated with a better outcome in terms of 7-year DFS.
  •  
41.
  • Sassa, Yasmine, et al. (author)
  • Investigation of the Magnetic Properties of Na0.7CoO2 Prepared by Electrochemical Reaction
  • 2018
  • In: JPS Conf. Proc. 21, 011019 (2018) [5 pages] Proceedings of the 14th International Conference on Muon Spin Rotation, Relaxation and Resonance (μSR2017). - : Physical Society of Japan.
  • Conference paper (peer-reviewed)abstract
    • We report a muon spin rotation and relaxation (μ+SR) study on Na0.7CoO2 powder samples, where the sodium (Na) has been intercalated via an electrochemical reaction inside a Na-ion battery. The zero field μ+SR measurement at T = 2 K shows a paramagnetic state for the as-grown sample whereas an antiferromagnetic (AF) ordered state is seen for the electrochemically cycled one. Furthermore, the temperature dependence of the muon-spin precession frequencies reveals a Néel transition temperature of TN = 22 K. The results demonstrate the importance of having high-quality homogenous samples, and put the existing NaxCoO2 magnetic phase diagram under debate.
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42.
  • Sassa, Yasmine, et al. (author)
  • The metallic quasi-1D spin-density-wave compound NaV2O4 studied by angle-resolved photoelectron spectroscopy
  • 2018
  • In: Journal of Electron Spectroscopy and Related Phenomena. - : ELSEVIER SCIENCE BV. - 0368-2048 .- 1873-2526. ; 224, s. 79-83
  • Journal article (peer-reviewed)abstract
    • Angle-resolved photoelectron spectroscopy has been used to follow the valence band and near Fermi edge electronic band structure in the quasi-1D compound NaV2O4. In this current study we have acquired the very first high-quality, high-resolution ARPES data from this material. Our data clearly reveal two distinct dispersive bands that cross the Fermi level at different k(F). This is a clear signature that the electronic properties of this material is affected by the presence of a mixed valence state on the different vanadium chains and possibly also the low-temperature magnetic spin order.
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43.
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44.
  • Sugiyama, J., et al. (author)
  • Desorption reaction in MgH 2 studied with in situ μ + SR
  • 2019
  • In: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 3:4, s. 956-964
  • Journal article (peer-reviewed)abstract
    • In order to study the mechanism determining the desorption temperature (T d ) of hydrogen storage materials, we have measured positive muon spin rotation and relaxation (μ + SR) in MgH 2 over a wide temperature range including its T d . The pressure in the sample cell due to desorbed H 2 was measured in parallel with the μ + SR measurements under static conditions. Such in situ μ + SR measurements revealed that hydrogen starts to diffuse in MgH 2 well below T d . This indicates the important role of hydrogen diffusion in accelerating the desorption reaction by removing the reaction product, i.e. H 2 , from the reaction system.
  •  
45.
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46.
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47.
  • Umegaki, Izumi, et al. (author)
  • Battery Materials Research with Muon Beam
  • 2019
  • In: Proceedings of the 3rd International Symposium of Quantum Beam Science at Ibaraki University "Quantum Beam Science in Biology and Soft Materials (ISQBSS2018). - : Physical society of Japan.
  • Conference paper (peer-reviewed)abstract
    • We applied a positive muon spin rotation and relaxation (μ+SR) technique to battery materials research by investigating Li diffusion in cathode and electrolyte materials. Recently, we have found that Li diffusion in graphite, which is commonly used as an anode material in Li-ion batteries, is detectable with μ+SR. Following upon the initial μ+SR measurements on the Li intercalated graphites, C6Li and C12Li, μ+SR spectra were also measured for C12Li0.92 and C18Li0.90 posing a slightly different occupancy in the same stage structure as those of C6Li and C12Li. The temperature dependence of diffusive nature in C12Li0.92 and C18Li0.90 was found to be similar in nature to those in C6Li and C12Li. Such a diffusion was found to start to occur approximately by 50 K lower than those of C6Li and C12Li. This suggests that Li starts to diffuse at lower temperatures in the nonstoichiometric Li intercalated graphite samples than that in the stoichiometric samples.
  •  
48.
  • Van Doorslaer, Koenraad, et al. (author)
  • ICTV virus taxonomy profile : Papillomaviridae
  • 2018
  • In: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 99:8, s. 989-990
  • Journal article (peer-reviewed)abstract
    • The Papillomaviridae is a family of small, non-enveloped viruses with double-stranded DNA genomes of 5 748 to 8 607 bp. Their classification is based on pairwise nucleotide sequence identity across the L1 open reading frame. Members of the Papillomaviridae primarily infect mucosal and keratinised epithelia, and have been isolated from fish, reptiles, birds and mammals. Despite a long co-evolutionary history with their hosts, some papillomaviruses are pathogens of their natural host species. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Papillomaviridae, which is available at http://www.ictv.global/report/papillomaviridae.
  •  
49.
  • Wu, Chengjun, et al. (author)
  • Short half-life of HPV16 E6 and E7 mRNAs sensitizes HPV16-positive tonsillar cancer cell line HN26 to DNA-damaging drugs
  • 2019
  • In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 144:2, s. 297-310
  • Journal article (peer-reviewed)abstract
    • Here we show that treatment of the HPV16-positive tonsillar cancer cell line HN26 with DNA alkylating cancer drug melphalan-induced p53 and activated apoptosis. Melphalan reduced the levels of RNA polymerase II and cellular transcription factor Sp1 that were associated with HPV16 DNA. The resulting inhibition of transcription caused a rapid loss of the HPV16 early mRNAs encoding E6 and E7 as a result of their inherent instability. As a consequence of HPV16 E6 and E7 down-regulation, the DNA damage inflicted on the cells by melphalan caused induction of p53 and activation of apoptosis in the HN26 cells. The BARD1-negative phenotype of the HN26 cells may have contributed to the failure to repair DNA damage caused by melphalan, as well as to the efficient apoptosis induction. Finally, nude mice carrying the HPV16 positive tonsillar cancer cells responded better to melphalan than to cisplatin, the chemotherapeutic drug of choice for tonsillar cancer. We concluded that the short half-life of the HPV16 E6 and E7 mRNAs renders HPV16-driven tonsillar cancer cells particularly sensitive to DNA damaging agents such as melphalan since melphalan both inhibits transcription and causes DNA damage.
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