| 1. |
- Arroyo Mühr, Laila Sara, et al.
(författare)
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Does human papillomavirus-negative condylomata exist?
- 2015
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Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 485, s. 283-288
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Tidskriftsartikel (refereegranskat)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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| 2. |
- 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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| 3. |
- Bzhalava, Davit, et al.
(författare)
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Deep sequencing extends the diversity of human papillomaviruses in human skin.
- 2014
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4:Jul 24
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Tidskriftsartikel (refereegranskat)abstract
- Most viruses in human skin are known to be human papillomaviruses (HPVs). Previous sequencing of skin samples has identified 273 different cutaneous HPV types, including 47 previously unknown types. In the present study, we wished to extend prior studies using deeper sequencing. This deeper sequencing without prior PCR of a pool of 142 whole genome amplified skin lesions identified 23 known HPV types, 3 novel putative HPV types and 4 non-HPV viruses. The complete sequence was obtained for one of the known putative types and almost the complete sequence was obtained for one of the novel putative types. In addition, sequencing of amplimers from HPV consensus PCR of 326 skin lesions detected 385 different HPV types, including 226 previously unknown putative types. In conclusion, metagenomic deep sequencing of human skin samples identified no less than 396 different HPV types in human skin, out of which 229 putative HPV types were previously unknown.
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| 4. |
- 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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| 5. |
- 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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| 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. |
- 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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| 9. |
- Hultin, Emilie, et al.
(författare)
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Viremia preceding multiple sclerosis : Two nested case-control studies
- 2018
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Ingår i: Virology. - : Elsevier. - 0042-6822 .- 1096-0341. ; 520, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Infections have been suggested to be involved in Multiple Sclerosis (MS). We used metagenomic sequencing to detect both known and yet unknown microorganisms in 2 nested case control studies of MS. Two different cohorts were followed for MS using registry linkages. Serum samples taken before diagnosis as well as samples from matched control subjects were selected.In cohort1 with 75 cases and 75 controls, most viral reads were Anelloviridae-related and >95% detected among the cases. Among samples taken up to 2 years before MS diagnosis, Anellovirus species TTMV1, TTMV6 and TTV27 were significantly more common among cases. In cohort2, 93 cases and 93 controls were tested under the pre-specified hypothesis that the same association would be found. Although most viral reads were again related to Anelloviridae, no significant case-control differences were seen. We conclude that the Anelloviridae-MS association may be due to multiple hypothesis testing, but other explanations are possible.
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| 10. |
- Lehtinen, Matti, et al.
(författare)
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Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers : Population-based follow-up of a cluster-randomised trial
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. Methods Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. Findings During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05). Interpretation Vaccination is effective against invasive HPV-positive cancer. Trial registration number NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
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