| 1. |
- Arroyo Mühr, Laila Sara, et al.
(författare)
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Improving human papillomavirus (HPV) testing in the cervical cancer elimination era : The 2021 HPV LabNet international proficiency study
- 2022
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 154, s. 105237-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proficient Human Papillomavirus (HPV) genotyping services are essential to support HPV and cervical cancer elimination strategies, in particular to support HPV vaccine research. Objectives: To perform a global HPV genotyping proficiency study, with evaluation in relation to previous proficiency studies. Study design: The proficiency panel contained 44 coded samples (40 samples containing one or more purified HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/68a/68b) in human DNA, 1 human DNA control and 3 DNA extraction controls). Proficiency required detection of both single and multiple infections of 50 International Units of HPV 16/18, of 500 genome equivalents for other HPV types and no false positivity. Results: One hundred and thirty-two laboratories submitted 211 datasets. Most assays used (182/211 datasets) were commercially available. An all-time high of 75% of the datasets were 100% proficient. One or more false positives were found in 17.5% of datasets. Among laboratories who participated in the 2019 proficiency study, full proficiency increased from 25% in 2019 to 60% in 2021. The high overall proficiency was mostly attributable to a large number of new laboratories, which used similar assays. Conclusions: The worldwide deterioration in comparability and reliability of HPV testing found in 2019 is now reversed and an overall increase in proficiency is found.
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| 2. |
- Axelsson, Jonatan, et al.
(författare)
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Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.
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| 3. |
- Carlander, Christina, et al.
(författare)
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HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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| 4. |
- Carlander, Christina, et al.
(författare)
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Nonvaccine human papillomavirus genotype common in women with HIV failing cervical precancer treatment
- 2021
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Ingår i: AIDS. - : Wolters Kluwer. - 0269-9370 .- 1473-5571. ; 35:14, s. 2367-2374
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess failure after treatment of high-grade cervical intraepithelial neoplasia (CIN2+) by HIV status and human papillomavirus (HPV) type.Design: A population-based register study.Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ sometime between 1983 and 2014 (n = 179). HIV-negative controls with CIN2+, were matched (2 : 1) for country of birth. CIN2+ biopsies were retrieved from biobanks and genotyped. Absolute risk and adjusted odds ratios (adjOR) of treatment failure by HIV status given HPV type (HPV16/18 vs. non-HPV16/18) were calculated.Results: HPV16 (32%) and HPV35 (24%) dominated in women living with HIV (WLWH) with failure, HPV35 mainly in women born in sub-Saharan Africa (67%). The absolute risk of failure in women with HPV16/18 was 26% [95% confidence interval (95% CI) 14-44] in WLWH and 12% in HIV-negative (95% CI 7-19). The absolute risk of failure in women with non-HPV16/18 was 20% (95% CI 12-31) in WLWH and 5% in HIV-negative (95% CI 2-11). WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative (adjOR 6.1, 95% CI 2.0-18.6).Conclusion: HPV35, not included in current HPV vaccines, was the second most common type in WLWH with failure. WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative. This could have implications for surveillance and vaccination post CIN2+ treatment, particularly in WLWH from sub-Saharan Africa.
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| 5. |
- Castro Dopico, Xaquin, et al.
(författare)
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Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates
- 2022
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Ingår i: Clinical & Translational Immunology (CTI). - : John Wiley & Sons. - 2050-0068. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50–99% likelihood, and 4.0% (n = 203) to have a 10–49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
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| 6. |
- Dillner, Joakim, et al.
(författare)
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Antibodies to SARS-CoV-2 and risk of past or future sick leave
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
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| 7. |
- Eklund, Carina, et al.
(författare)
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The 2019 HPV Labnet international proficiency study : Need of global Human Papillomavirus Proficiency Testing
- 2021
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 141, s. 104902-
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Tidskriftsartikel (refereegranskat)abstract
- Background:: Accurate and internationally comparable human papillomavirus (HPV) testing services are essential for cervical cancer elimination programs. The WHO HPV Laboratory Network started issuing international HPV testing proficiency panels in 2008. Objectives:: We report the results of the 2019 global proficiency study and evaluate the proficiency over time. Study design:: The proficiency panel contained 40 coded samples containing mixes of purified HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/68a/68b) and 4 controls. Proficiency required detection of both single and multiple infections of 50 International Units of HPV 16/18, of 500 genome equivalents (10x higher concentration) for other HPV types, and no false positives (stricter requirement compared to previous panels). Results:: Seventy-eight laboratories submitted 110 datasets with 38 different assays. Most samples (38/44) were reported with 100% proficiency in most datasets. Mostly commercial assays were used (88/110 datasets). Overall, 47.3% of the datasets were 100% proficient. False positivity was detected in at least one sample in 30.1% of datasets. When analysing all datasets ever since 2008 using exactly the same proficiency criteria, there was a steady improvement up to 2017 (the proportion of datasets being completely proficient increased from 25% to 73%). However, in the 2019 proficiency testing the proportion of fully proficient datasets dropped to 50%. Conclusions:: Although we initially documented a worldwide improvement in comparability and reliability of HPV testing services, the trend now appears to be reversed. In response, the International HPV Reference Center will provide support for improved quality of laboratory services, including issuing of global proficiency panels every year.
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| 8. |
- Elfstrom, K. Miriam, et al.
(författare)
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Differences in risk for SARS-CoV-2 infection among healthcare workers
- 2021
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Ingår i: Preventive Medicine Reports. - : Elsevier BV. - 2211-3355. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n = 15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n = 12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.
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| 9. |
- Garcia-Serrano, Ainhoa, et al.
(författare)
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Assessment of bacterial and viral gut communities in healthy and tumoral colorectal tissue using RNA and DNA deep sequencing
- 2023
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Ingår i: Cancer Medicine. - 2045-7634. ; 12:18, s. 19291-19300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer (CRC) is known to present a distinct microbiome profile compared to healthy mucosa. Non-targeted deep-sequencing strategies enable nowadays full microbiome characterization up to species level. Aim: We aimed to analyze both bacterial and viral communities in CRC using these strategies. Materials & Methods: We analyzed bacterial and viral communities using both DNA and RNA deep-sequencing (Novaseq) in colorectal tissue specimens from 10 CRC patients and 10 matched control patients. Following taxonomy classification using Kraken 2, different metrics for alpha and beta diversities as well as relative and differential abundance were calculated to compare tumoral and healthy samples. Results: No viral differences were identified between tissue types, but bacterial species Polynucleobacter necessarius had a highly increased presence for DNA in tumors (p = 0.001). RNA analyses showed that bacterial species Arabia massiliensis had a highly decreased transcription in tumors (p = 0.002) while Fusobacterium nucleatum transcription was highly increased in tumors (p = 0.002). Discussion: Sequencing of both DNA and RNA enables a wider perspective of micriobiome profiles. Lack of RNA transcription (Polynucleobacter necessarius) casts doubt on possible role of a microorganism in CRC. The association of F. nucleatum mainly with transcription, may provide further insights on its role in CRC. Conclusion: Joint assessment of the metagenome (DNA) and the metatranscriptome (RNA) at the species level provided a huge coverage for both bacteria and virus and identifies differential specific bacterial species as tumor associated.
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| 10. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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