Klara Miriam Elfström

Karolinska Institutet | KI · Department of Laboratory Medicine

Background Prediction of SARS-CoV-2-induced sick leave among healthcare workers (HCWs) is essential for being able to plan the healthcare response to the epidemic. Methods During first wave of the SARS-Cov-2 epidemic (April 23 rd to June 24 th , 2020), the HCWs in the greater Stockholm region in Sweden were invited to a study of past or present SA...

PURPOSE Detection of human papillomavirus (HPV) by polymerase chain reaction in invasive cervical cancer is strongly associated with prognosis but previous studies have not considered sequencing efforts. We aimed to assess the association when also including comprehensive analysis of HPV infection by deep sequencing and a longer follow-up period....

A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify potential infectiousness among asymptomatic healthcare workers (HCWs) in relation to prior or later symptomatic disease. We previously (at the onset of the SARS-CoV-2 epidemic) performed...

Objectives Most COVID-19 related infections and deaths may occur in healthcare outside hospitals. Here we explored SARS-CoV-2 infections among healthcare workers (HCWs) in this setting. Design All healthcare providers in Stockholm, Sweden were asked to recruit HCWs at work for a study of past or present SARS-CoV-2 infections among HCWs. Study part...

Human Papillomavirus (HPV) infection is a necessary risk factor for cervical cancer. If HPV is no longer spread, no new cervical cancer precursors will occur. The timepoint for control of the HPV infection will therefore be a rate-limiting step for cervical cancer elimination. We used a validated dynamic HPV transmission model to estimate the age-s...

Background Clinical trials in the research setting have demonstrated that primary human papillomavirus (HPV)-based screening results in greater protection against cervical cancer compared with cytology, but evidence from real-life implementation was missing. To evaluate the effectiveness of HPV-based cervical screening within a real-life screening...

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-C...

Background: Cervical screening programs target entire populations, although it is well established that cervical cancer risks can vary >100-fold based, in particular, on the woman’s screening history. Since cervical screening switched to Human Papillomavirus (HPV) testing as the primary screening method, the risk differences are even larger as diff...

Aim We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs). Methods From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Pr...

Most Covid-related infections and deaths occur in healthcare outside hospitals. We wished to explore SARS-CoV-2 infections among healthcare workers (HCWs) in this setting. All healthcare providers in Stockholm, Sweden were asked to invite HCWs at work for a study of past or present SARS-CoV-2 infections among HCWs. This study reports the results fr...

Background In Sweden, home care services is a major external contact for older persons. Methods Five home care service companies in Stockholm, Sweden, enrolled 405 employees to a study including serum IgG to SARS‐CoV‐2 and SARS‐CoV‐2 virus in throat swabs. Results 20.1% (81/403) of employees were seropositive, about twice as many as in a simultan...

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 employe...

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50–69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in f...

Background: Whether SARS-CoV-2 positivity among symptomatic subjects reflects past or future disease may be difficult to ascertain. Methods: We tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the testing results to sick leave records and determined assoc...

We found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11·97 (CI 95% 6·29-22·80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR...

Total excess mortality peaked during a COVID19 outbreak in Stockholm, but 25% of these deaths were not recognized as Covid-19-related nor occurred in hospitals. Estimate of total excess mortality may give a more comprehensive picture of the total disease burden during a COVID19 outbreak, and may facilitate managing future outbreaks.

Total excess mortality peaked during a COVID19 outbreak in Stockholm, but 25% of these deaths were not recognized as Covid-19-related nor occurred in hospitals. Estimate of total excess mortality may give a more comprehensive picture of the total disease burden during a COVID19 outbreak, and may facilitate managing future outbreaks.

Background: The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. Method: We analyzed 12928 healthy hospital employees for SARS-CoV-2 antibodies and compared results to participant sick leave records (Clinical trial registration: ClinicalTrials.gov NCT04411576). Results: Subjects with viral serum a...

We compared the total excess mortality per week in relation to the reported Covid-19 related deaths in the Stockholm region (Sweden). Total excess mortality peaked under the weeks of high COVID-19 related mortality, but 25% of these deaths were not recognized as Covid- elated. Most of these deaths occurred outside hospitals. Total all-cause mortali...

Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology. We included 153,250 girls born between 1989 and 1993, resident in Sweden since the introduction of HPV vaccines (October 2006) and attending cervical screening at age 23 years. We assessed their first cytology and following histopathologica...

A screening program for abdominal aortic aneurysm (AAA), inviting 65-year-old men, was started in Stockholm in 2010 (2.3 million inhabitants). The aim was to present a long-term follow-up of men participating in screening, as well as AAA repair and ruptures among nonparticipants. Demographics were collected for men with screening detected with AAA...

Introduction: Emergency contraceptive pill (ECP) use is reported to have increased in several countries over time. In this multi-country population-based questionnaire study, we aimed to describe the patterns of ECP use and identify factors associated with its use. Material and methods: In 2011-2012, women aged 18-45 years were randomly selected...

With major advances in understanding the infectious etiology of cervical cancer, preventive medicine has obtained highly promising new tools. Human papillomavirus (HPV) vaccines, together with a growing arsenal of HPV-based screening tests, have the potential to radically change public health but require diligent, large-scale implementation to reac...

Background: Human Papillomavirus (HPV)-based screening has a higher sensitivity for precursors of cervical cancer compared to cytology-based screening. However, more evidence is needed on optimal management of HPV-positive women. Objective: To compare the risk of histopathologically confirmed CIN2+ after 1 and 3 years of HPV persistence, respect...

Introduction: Sexual behavior at the population level impact on public health. Recent representative sexual behavior data is lacking. Material and methods: Cross-sectional surveys in 2005 and 2012 on women age 18-45 randomly selected from the general population in Denmark (N=40804), Norway (N=30331) and Sweden (N=32114). Results: Median (inter...

High screening participation in the population is essential for optimal prevention of cervical cancer. Offering a high‐risk human papillomavirus (HPV) self‐test has previously been shown to increase participation. In this randomized health services study, we evaluated 4 strategies with regard to participation. Women who had not attended organized c...

Objectives To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC. Design Nationwide, population based, nested case-control stu...

Objective: Women's contraceptive use at first sexual intercourse (FSI) may be associated with subsequent sexual behaviors. We examined associations between contraceptive methods used at FSI and subsequent number of lifetime partners, induced abortions and sexually transmitted infections (STIs). Study design: During 2011-2012, we collected questi...

Background: To enable incremental optimization of screening, regular reporting of quality indicators is required. Aim: To report key quality indicators and basic statistics about cervical screening in Sweden. Methods: We collected individual level data on all cervical cytologies, histopathologies, human papillomavirus tests and all invitations...

Objective: Using quantitative Faecal Immunochemical Test (FIT) in colorectal cancer screening enables adjustment of the cut-off for a positive test. As men have higher stool blood levels and higher prevalence of colorectal neoplasia, different cut-off levels can be chosen for men and women. We evaluated participation and positivity rates switching...

Background High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comp...

Characteristics of confirmed cases by availability of valid blocks. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status, by age at cancer diagnosis. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status, by FIGO stage. (DOCX)

One-year, 3-year, 5-year, and 10-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status, in high-grade tumors. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status, by mode of detection. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status based on L1 region and HPV16-E7/HPV18-E6. (DOCX)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status based on L1 region and HPV16-E7/HPV18-E6, by FIGO stage. (DOCX)

Other supporting tables and figures. (PDF)

Five-year relative survival ratios (RSRs) and 5-year excess hazard ratios (EHRs) in relation to high-risk human papillomavirus (hrHPV) status based on L1 region and HPV16-E7/HPV18-E6, by age at cancer diagnosis. (DOCX)

Tumor human papillomavirus (HPV) status and pre-diagnostic HPV testing results. (DOCX)

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...

Introduction: The aim was to assess cost-effectiveness of expanding the Swedish HPV-vaccination program to include preadolescent boys, by comparing health-effects and costs of HPV-related disease, with a sex-neutral vaccination program versus only vaccinating girls. Methods: We used a dynamic compartmental model to simulate the burden of HPV16/1...

Objectives: The organized population-based screening programme for abdominal aortic aneurysm in Stockholm, Sweden, started in 2010. An examination fee was initially charged, but later removed because of a policy change. We examined the effect on screening attendance of removing the fee. Methods: The periods before and after removing the examinat...

Knowledge of determinants of anal HPV infections among men is still limited as most of the studies are focused on high‐risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of a...

Background: The Swedish National Cervical Screening Registry collects and evaluates comprehensive, nationwide health data to optimise organised cervical cancer prevention. Since all cervical cancer specimens are saved in biobanks, population-based data from the specimens should be available for analysis and linkage with other health information....

Background: The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening h...

Time of initiating cervical screening records by counties/hospitals. (PNG)

Distribution of the time between Pap test and cancer diagnosis for distinguishing diagnostic workup Pap test from screening Pap test, in women diagnosed with invasive cervical cancer at age 61–65 years in 2002–2011. Mode of detection of cervical cancer (i.e., screen-detected or symptomatic) was retrieved from medical charts. It was then linked with...

Supporting tables. (DOCX)

Analysis protocol. (DOCX)

Objectives: To assess patterns and probabilities of participation in multiple rounds of colorectal cancer screening. Methods: All individuals who were invited to participate in population-based colorectal cancer screening in the Stockholm-Gotland region in Sweden between 1 January 2008 and 30 September 2015 were included in the study. Guaiac-bas...

Objective The aim of this research is to implement and reliably evaluate primary human papillomavirus (HPV) screening in an established and routinely running organised, large-scale population-based screening programme. Participants Resident women in the Stockholm/Gotland region of Sweden, aged 56–60 years were randomised to either (1) screening wi...

Background: While vaccine-induced antibodies are known to confer protection against incident human papillomavirus (HPV) infection, there is inconsistent data regarding the protective effect of naturally acquired anti-HPV antibodies. Objectives: To estimate the protective effect of naturally acquired anti-HPV16 serum antibodies against incident a...

Background: Introduction of human papillomavirus-based screening is ongoing in many countries, given its higher sensitivity and longer-lasting protection compared with cytology-based screening. However, optimal clinical management of human papillomavirus-positive but cytology-negative women is unclear, and additional studies with clinical follow-u...

Background: Atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden and comparative effectiveness studies of different management options for such diagnoses are needed. Objective: To co...

Objectives: Comprehensive nationwide monitoring and evaluation of screening through registry-based review of key indicators is necessary for programme optimization, especially as new tests and strategies are introduced. We aimed to investigate and report on the use of these key indicators in the Swedish programme. Setting and methods: Organized...

Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any...

Appendix 2: Supplementary figures A-B

Appendix 1: Supplementary tables A-E

Objective: This study aims to identify possible barriers to and facilitators of cervical cancer screening by (a) estimating time and travel costs and other direct non-medical costs incurred in attending clinic-based cervical cancer screening, (b) investigating screening compliance and reasons for noncompliance, (c) determining women's knowledge of...

Background: Decreasing human papillomavirus (HPV) vaccine prices makes scaling up of vaccination programs attractive for countries that initially targeted 1 or a few birth cohorts of girls and/or achieved low coverage. This article aims to compare the impact of alternative HPV vaccination strategies, using data from Sweden, a high-income country t...

Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2...

Cervical screening programmes have reduced cervical cancer incidence and mortality but the level of success is highly variable between countries. Organisation of programmes is essential for equity and cost-effectiveness. However, there are differences in effectiveness, also among organised programmes. In order to identify the key organisational com...

HPV vaccination is underway in most European countries, but there are limited efforts toward optimization and standardization of organization, monitoring and evaluation. Our Europe-wide survey sought to identify how programs are currently organized, the costs associated with the organizing and ensuring quality of the program and how quality and eff...