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1. Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

Author

Koenecke, Allison, Powell, Michael, Xiong, Ruoxuan, Shen, Zhu, Fischer, Nicole, Huq, Sakibul, Khalafallah, Adham M., Trevisan, Marco, Sparen, Pär, Carrero, Juan J, Nishimura, Akihiko, Caffo, Brian, Stuart, Elizabeth A., Bai, Renyuan, Staedtke, Verena, Thomas, David L., Papadopoulos, Nickolas, Kinzler, Kenneth W., Vogelstein, Bert, Zhou, Shibin, Bettegowda, Chetan, Konig, Maximilian F., Mensh, Brett, Vogelstein, Joshua T., and Athey, Susan

Subjects
Quantitative Biology - Tissues and Organs, Quantitative Biology - Quantitative Methods
Abstract

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($\alpha_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $\alpha_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $\alpha_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19., Comment: 31 pages, 10 figures

Published
2020
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2. Incidence of oncogenic HPV infection in women with and without mental illness: A population-based cohort study in Sweden

Author

Herweijer, Eva, Hu, Kejia, Wang, Jiangrong, Lu, Donghao, Sparén, Pär, Adami, Hans-Olov, Valdimarsdóttir, Unnur, Sundström, Karin, and Fang, Fang

Subjects
Women -- Analysis -- Usage -- Health aspects, Sexually transmitted diseases -- Analysis -- Usage, Antidepressants -- Usage, Mentally ill -- Analysis -- Usage, Papillomavirus infections -- Usage -- Analysis, Tranquilizing drugs -- Usage -- Analysis, Infection -- Usage -- Analysis, Cervical cancer -- Analysis -- Usage, Mediation -- Analysis -- Usage, Mental illness -- Usage -- Analysis, Biological sciences, World Health Organization
Abstract

Background Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. Methods and findings Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. Conclusions Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide., Author(s): Eva Herweijer 1, Kejia Hu 1,*, Jiangrong Wang 2, Donghao Lu 1, Pär Sparén 3, Hans-Olov Adami 3,4, Unnur Valdimarsdóttir 1,5,6, Karin Sundström 2, Fang Fang 1,* Introduction Cervical [...]

Published
2024
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3. Impact of cervical screening by human papillomavirus genotype: Population-based estimations

Author

Wang, Jiangrong, Elfström, K. Miriam, Lagheden, Camilla, Eklund, Carina, Sundström, Karin, Sparén, Pär, and Dillner, Joakim

Subjects
Oncology, Experimental -- Usage -- Genetic aspects, Women -- Health aspects, Cancer -- Diagnosis -- Prevention -- Research, Papillomaviruses -- Genetic aspects, Papillomavirus infections -- Genetic aspects, Cervical cancer -- Genetic aspects, Biological sciences, World Health Organization
Abstract

Background Cervical screening programs use testing for human papillomavirus (HPV) genotypes. Different HPV types differ greatly in prevalence and oncogenicity. We estimated the impact of cervical screening and follow-up for each HPV type. Methods and findings For each type of HPV, we calculated the number of women needed to screen (NNS) and number of women needing follow-up (NNF) to detect or prevent one cervical cancer case, using the following individual level input data (i) screening and cancer data for all women aged 25 to 80 years, resident in Sweden during 2004 to 2011 (N = 3,568,938); (ii) HPV type-specific prevalences and screening histories among women with cervical cancer in Sweden in 2002 to 2011(N = 4,254); (iii) HPV 16/18/other HPV prevalences in the population-based HPV screening program (N = 656,607); and (iv) exact HPV genotyping in a population-based cohort (n = 12,527). Historical screening attendance was associated with a 72% reduction of cervical cancer incidence caused by HPV16 (71.6%, 95% confidence interval (CI) [69.1%, 73.9%]) and a 54% reduction of cancer caused by HPV18 (53.8%, 95% CI [40.6%, 63.1%]). One case of HPV16-caused cervical cancer could be prevented for every 5,527 women attending screening (number needed to screen, NNS). Prevention of one case of HPV16-caused cervical cancer required follow-up of 147 HPV16-positive women (number needed to follow-up, NNF). The NNS and NNF were up to 40 to 500 times higher for HPV types commonly screened for with lower oncogenic potential (HPV35,39,51,56,59,66,68). For women below 30 years of age, NNS and NNF for HPV16 were 4,747 and 289, respectively, but >220,000 and >16,000 for HPV35,39,51,56,59,66,68. All estimates were either age-standarized or age-stratified. The primary limitation of our study is that NNS is dependent on the HPV prevalence that can differ between populations and over time. However, it can readily be recalculated in other settings and monitored when HPV type-specific prevalence changes. Other limitations include that in some age groups, there was little data and extrapolations had to be made. Finally, there were very few cervical cancer cases associated with certain HPV types in young age group. Conclusions In this study, we observed that the impact of cervical cancer screening varies depending on the HPV type screened for. Estimating and monitoring the impact of screening by HPV type can facilitate the design of effective and efficient HPV-based cervical screening programs. Trial registration ClinicalTrials.gov with numbers NCT00479375, NCT01511328., Author(s): Jiangrong Wang 1, K. Miriam Elfström 1,2, Camilla Lagheden 1, Carina Eklund 1, Karin Sundström 1, Pär Sparén 3, Joakim Dillner 1,2,* Introduction Elimination of cervical cancer as a [...]

Published
2023
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7. Long-term follow-up of cervical cancer incidence after normal cytological findings

Author

Wang, Jiangrong, Edvardsson, Henrik, Strander, Björn, Andrae, Bengt, Sparén, Pär, Dillner, Joakim, Wang, Jiangrong, Edvardsson, Henrik, Strander, Björn, Andrae, Bengt, Sparén, Pär, and Dillner, Joakim

Abstract

An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.

Published
2024
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12. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Author

Ali, Hammad, Boily, Marie-Claude, Baldo, Vincenzo, Brassard, Paul, Brotherton, Julia M L, Callander, Denton, Checchi, Marta, Chow, Eric P F, Cocchio, Silvia, Dalianis, Tina, Deeks, Shelley L, Dehlendorff, Christian, Donovan, Basil, Fairley, Christopher K, Flagg, Elaine W, Gargano, Julia W, Garland, Suzanne M, Grün, Nathalie, Hansen, Bo T, Harrison, Christopher, Herweijer, Eva, Imburgia, Teresa M, Johnson, Anne M, Kahn, Jessica A, Kavanagh, Kimberley, Kjaer, Susanne K, Kliewer, Erich V, Liu, Bette, Machalek, Dorothy A, Markowitz, Lauri, Mesher, David, Munk, Christian, Niccolai, Linda, Nygård, Mari, Ogilvie, Gina, Oliphant, Jeannie, Pollock, Kevin G, Purriños-Hermida, Maria Jesús, Smith, Megan A, Steben, Marc, Söderlund-Strand, Anna, Sonnenberg, Pam, Sparen, Pär, Tanton, Clare, Wheeler, Cosette M, Woestenberg, Petra J, Yu, Bo Nancy, Drolet, Mélanie, Bénard, Élodie, Pérez, Norma, and Brisson, Marc

Published
2019
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30. COVID-19 hospitalization outcomes in adults by HIV status; a nation-wide register-based study

Author

Möller, Isabela Killander, Gisslén, Magnus, Wagner, Philippe, Sparén, Pär, Carlander, Christina, Möller, Isabela Killander, Gisslén, Magnus, Wagner, Philippe, Sparén, Pär, and Carlander, Christina

Abstract

Objectives: To assess the outcome of patients hospitalized with COVID-19 by HIV status and risk factors for severe COVID-19 in people living with HIV (PWH), we performed a nationwide cohort study using register data. Methods: All people aged >= 18 years hospitalized with a primary COVID-19 diagnosis (U07.1 or U07.2) in Sweden between February 2020 and October 2021 were included. The primary outcome was severe COVID-19 [intensive care unit (ICU) admission or 90-day mortality]. Secondary outcomes were days in hospital and ICU, complications in hospital, and risk factors for severe COVID-19 in PWH. Regression analyses were performed to assess severe COVID-19 by HIV status and risk factors. Results: Data from 64 815 hospitalized patients were collected, of whom 121 were PWH (0.18%). PWH were younger (p < 0.001), and larger proportions were men (p = 0.014) and migrants (p < 0.001). Almost all PWH had undetectable HIV-RNA (93%) and high CD4 T-cell counts (median = 560 cells/mu L, interquartile range: 376-780). In an unadjusted model, PWH had statistically significant lower odds of severe COVID-19 compared with patients without HIV [odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.34-0.94], but there was no significant difference after adjusting for age and comorbidity (adjusted OR = 0.7, 95% CI: 0.43-1.26). A statistically significant lower proportion of PWH (8%, 95% CI: 5-15%) died within 90 days compared with those without HIV (16%, 95% CI: 15-16%, p = 0.024). There was no statistically significant difference in days in hospital and complications during the hospital stay between PWH and patients without HIV. Conclusions: In this nationwide study including well-treated PWH, HIV was not a risk factor in hospitalized patients for developing severe COVID-19.

Published
2023
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31. Pregnancy outcomes in women with a prior cervical intraepithelial neoplasia grade 3 diagnosis : a nationwide population-based cohort study with sibling comparison design

Author

He, Wei, Sparén, Pär, Fang, Fang, Sengpiel, Verena, Strander, Björn, Czene, Kamila, He, Wei, Sparén, Pär, Fang, Fang, Sengpiel, Verena, Strander, Björn, and Czene, Kamila

Abstract

Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. Objective: To investigate pregnancy outcomes in women diagnosed with CIN3. Design: Population- and sibling-matched cohort study. Setting: Sweden, 1973-2018. Participants: General population comparison included 78 450 singletons born to women diagnosed with CIN3 and 784 500 matched singletons born to women in the general population who had no CIN3 diagnosis; sibling comparison included 23 199 singletons born to women diagnosed with CIN3 and 28 135 singletons born to their sisters without a CIN3 diagnosis. Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; Infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. Results: Compared with the matched general population, women previously diagnosed with CIN3 were more likely to have a preterm birth especially extremely preterm (22-28 weeks; OR, 3.00; 95% CI, 2.69-3.34) and spontaneous preterm (OR, 2.12; 95% CI, 2.05-2.20) birth, infection-related outcomes including chorioamnionitis (OR, 3.23; 95% CI, 2.89-3.62) and infant sepsis (OR, 1.72; 95% CI, 1.60-1.86), and early neonatal death (OR, 1.83; 95% CI, 1.61-2.09). Sibling comparison analyses rendered largely similar results. Over time the risk difference attenuated for all outcomes and disappeared for early neonatal death. Limitations: Lack of data on CIN3 treatment and spontaneous abortion. Conclusion: Prior history of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN3 may be minimized by improving treatment modalities.

Published
2023

34. Experience and evaluation of the effectiveness of vaccination against HPV on the example of Sweden : Information based on data from the article «Substantially reduced incidence of genital warts in women and men six years after HPV vaccine availability in Sweden»

Author

Herweijer, Eva, Ploner, Alexander, and Sparén, Pär

Subjects
HPV, вакцинація, населення, vaccine, вірус папіломи людини, кондилома, condyloma, population-level
Abstract

Between 2007 and 2011, opportunistic HPV-vaccination was available in Sweden and partially subsidized to girls aged 13–17, reaching a 30% overall coverage.Methods: All Swedish women/men aged 15–44 were followed between 2006 and 2012 for condyloma.Average annual percent changes (AAPCs) in incidence were estimated.Results: Substantial decreases were seen in women aged 15–24 from 2008-onwards (AACP-range: 8.5% to 18.5%); similar effects were seen for men aged 15–29 (AACP-range: 7.0% to 16.6%) from 2010-onwards.Discussion: Despite low population vaccination coverage in women and no coverage in men, similar condyloma incidence reductions were observed among men and women, with delays of >1 years in men., У період з 2007 до 2011р. опортуністична вакцинація проти ВПЛ була доступна у Швеції, і витрати на неї частково покривались для дівчат віком 13–17 років, досягаючи загального охоплення вакцинацією на рівні 30%. Методи. Усі жінки/чоловіки віком 15–44 років, у яких виявлено кондиломи, у Швеції у період між 2006 та 2012рр.Проведено оцінювання середньорічних відсоткових змін (аverage annual percent changes – AAPCs) частоти захворюваності.Результати. З 2008р. спостерігалось значне зменшення захворюваності у жінок віком 15–24 років (діапазон AAPC: з –8,5% до –18,5%); подібний ефект відзначено і у чоловіків віком 15–29 років (діапазон AAPC: з –7,0% до –16,6%), починаючи з 2010р. і далі.Висновки. Незважаючи на низьке охоплення вакцинацією жіночого населення та відсутність охоплення щепленням чоловіків, відзначено зниження захворюваності на кондиломи серед чоловіків та жінок із затримкою >1 року для чоловіків.

Published
2023

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