Concomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer.

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.

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

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.

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells.

OBJECTIVE: To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. METHODS: This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. RESULTS: Of 341 women, 134 (39.3%) had CIN 3-AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0-97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47-5.00 and HR 3.41, 95% CI 1.95-5.96, respectively). CONCLUSION: Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening.

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41. To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40-42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

Cost-effectiveness of Prostate Cancer Screening Using Magnetic Resonance Imaging or Standard Biopsy Based on the STHLM3-MRI Study.

Importance: The combination of prostate-specific antigen (PSA) testing with magnetic resonance imaging (MRI) for prostate cancer detection has rarely been evaluated in a screening context. The STHLM3-MRI screening-by-invitation study (NCT03377881) has reported the benefits of using MRI with subsequent combined targeted and standard biopsies compared with using standard biopsies alone. Objective: To investigate the cost-effectiveness of prostate cancer screening using MRI with combined targeted and standard biopsies compared with standard biopsies alone among men aged 55 to 69 years in Sweden, based on evidence from the STHLM3-MRI study. Design, Setting, and Participants: This economic evaluation study was conducted from a lifetime health care perspective using a microsimulation model to evaluate no screening and screening strategies among adult men in Sweden. Men aged 55 to 69 years in Sweden were simulated for no screening and screening strategies. Input parameters were obtained from the STHLM3-MRI study and recent reviews. One-way and probabilistic sensitivity analyses were performed in May 2022. Interventions: No screening, quadrennial PSA screening using standard biopsies alone, and MRI-based screening using combined targeted and standard biopsies. Main Outcomes and Measures: The number of tests, incidence, deaths, costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICERs) were estimated. Results: A total 603 men were randomized to the standard arm, 165 of these participants (27.4%) did not undergo standard biopsy; 929 men were randomized to the experimental arm, 111 (11.9%) of whom did undergo MRI or any biopsy. Compared with no screening, the screening strategies were associated with reduced lifetime prostate cancer-related deaths by 6% to 9%. Screening with MRI and the combined biopsies resulted in an ICER of US $53 736, which is classified as a moderate cost per QALY gained in Sweden. Relative to screening with standard biopsies alone, MRI-based screening reduced the number of both lifetime biopsies and overdiagnosis by approximately 50% and had a high probability of being cost-effective than the traditional PSA screening. Conclusions and Relevance: For prostate cancer screening, this economic evaluation study found that PSA testing followed by MRI with subsequent combined targeted and standard biopsies had a high probability to be more cost-effective compared with the traditional screening pathway using PSA and standard biopsy. MRI-based screening may be considered for early detection of prostate cancer in Sweden.

Cost-Effectiveness of Magnetic Resonance Imaging in Prostate Cancer Screening: A Microsimulation Study.

OBJECTIVE: This study aimed to assess the cost-effectiveness of magnetic resonance imaging (MRI) with combinations of targeted biopsy (TBx) and systematic biopsy (SBx) for early prostate cancer detection in Sweden. METHODS: A cost-utility analysis was conducted from a lifetime societal perspective using a microsimulation model. Five strategies included no screening and quadrennial screening for men aged 55 to 69 years using SBx alone, TBx on positive MRI (MRI + TBx), combined TBx/SBx on positive MRI (MRI + TBx/SBx), and SBx on negative MRI with TBx/SBx on positive MRI (MRI - SBx, MRI + TBx/SBx). Test characteristics were based on a recent Cochrane review. We predicted the number of biopsies, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. RESULTS: The screening strategies were classified in Sweden as high costs per QALY gained compared with no screening. Using MRI + TBx and MRI + TBx/SBx reduced the number of biopsy episodes across a lifetime by approximately 40% compared with SBx alone. Both strategies showed strong dominance over SBx alone and MRI - SBx, MRI + TBx. Compared with MRI + TBx, the MRI + TBx/SBx strategy had an incremental cost-effectiveness ratio of more than €200 000 per QALY gained, which was classified in Sweden as a very high cost. These predictions were robust in the probabilistic sensitivity analysis. Limitations included generalizability of the model assumptions and uncertainty regarding the health-state values and study heterogeneity from the Cochrane review. CONCLUSIONS: MRI + TBx and MRI + TBx/SBx showed strong dominance over alternative screening strategies. MRI + TBx resulted in similar or marginally lower gains in QALYs and lower costs than MRI + TBx/SBx. MRI + TBx was considered the optimal choice among the screening strategies.

Prospects for accelerated elimination of cervical cancer.

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-specific HPV16 incidences and basic reproductive numbers (R0) with input data from Sweden. If R0 is below 1, a fade-out resulting in extinction is expected. Above age 35, we found an R0 of 0.4. Thus, when younger birth cohorts no longer transmit HPV to women >35 years of age, we predict that the HPV infection will no longer be sustained among the older women. Given adequate resources, campaigns to eliminate HPV that are designed based on the R0 measurements followed by screening to detect and treat pre-existing cervical cancer precursors could achieve accelerated cervical cancer elimination.

Risk for SARS-CoV-2 infection in healthcare workers outside hospitals: A real-life immuno-virological study during the first wave of the COVID-19 epidemic.

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 participants This study reports the results from 839 HCWs, mostly employees of primary care centers, sampled in June 2020. RESULTS: SARS-CoV-2 seropositivity was found among 12% (100/839) of HCWs, ranging from 0% to 29% between care units. Seropositivity decreased by age and was highest among HCWs <40 years of age. Within this age group there was 19% (23/120) seropositivity among women and 11% (15/138) among men (p<0.02). Current infection, as measured using PCR, was found in only 1% and the typical testing pattern of pre-symptomatic potential "superspreaders" found in only 2/839 subjects. CONCLUSIONS: Previous SARS-CoV-2 infections were common among younger HCWs in this setting. Pre-symptomatic infection was uncommon, in line with the strong variability in SARS-CoV-2 exposure between units. Prioritizing infection prevention and control including sufficient and adequate personal protective equipment, and vaccination for all HCWs are important to prevent nosocomial infections and infections as occupational injuries during an ongoing pandemic.

Exposure Definition in Case-Control Studies of Cervical Cancer Screening: A Systematic Literature Review.

The first step in evaluating the effectiveness of cervical screening is defining exposure to screening. Our aim was to describe the spectrum of screening exposure definitions used in studies of the effectiveness of cervical screening. This systematic review included case-control studies in a population-based screening setting. Outcome was incidence of cervical cancer. Three electronic databases were searched from January 1, 2012 to December 6, 2018. Articles prior to 2012 were identified from a previous review. The qualitative synthesis focused on describing screening exposure definitions reported in the literature and the methodologic differences that could have an impact on the association between screening and cervical cancer. Forty-one case-control studies were included. Six screening exposure definitions were identified. Cervical cancer risk on average decreased by 66% when screening exposure was defined as ever tested, by 77% by time since last negative test, and by 79% after two or more previous tests. Methodologic differences included composition of the reference group and whether diagnostic and/or symptomatic tests were excluded from the analysis. Consensus guidelines to standardize exposure definitions are needed to ensure evaluations of cervical cancer screening can accurately measure the impact of transitioning from cytology to human papillomavirus-based screening and to allow comparisons between programs.

Differences in risk for SARS-CoV-2 infection among healthcare workers.

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.

Organized primary human papillomavirus-based cervical screening: A randomized healthcare policy trial.

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 program, the organized, population-based cervical screening program in the capital region of Sweden offered either HPV- or cytology-based screening in a randomized manner through a randomized healthcare policy (RHP). METHODS AND FINDINGS: A total of 395,725 women aged 30 to 64 years that were invited for their routine cervical screening visit were randomized without blinding to either cytology-based screening with HPV triage (n = 183,309) or HPV-based screening, with cytology triage (n = 212,416 women) between September 1, 2014 and September 30, 2016 and follow-up through June 30, 2017. The main outcome was non-inferior detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Secondary outcomes included superiority in CIN2+ detection, screening attendance, and referral to histology. In total, 120,240 had a cervical screening sample on record in the study period in the HPV arm and 99,340 in the cytology arm and were followed for the outcomes of interest. In per-protocol (PP) analyses, the detection rate of CIN2+ was 1.03% (95% confidence interval (CI) 0.98 to 1.10) in the HPV arm and 0.93% (0.87 to 0.99) in the cytology arm (p for non-inferiority <0.0001; odds ratio (OR) 1.11 (95% CI 1.02 to 1.22)). There were 46 cervical cancers detected in the HPV arm (0.04% (0.03 to 0.06)) and 48 cancers detected in the cytology arm (0.05% (0.04 to 0.07)) (p for non-inferiority <0.0001; OR 0.79 (0.53 to 1.18)). Intention-to-screen (ITS) analyses found few differences. In the HPV arm, there was a modestly increased attendance after new invitations (68.56% (68.31 to 68.80) vs. 67.71% (67.43 to 67.98); OR 1.02 (1.00 to 1.03)) and increased rate of referral with completed biopsy (3.89% (3.79 to 4.00) vs. 3.53% (3.42 to 3.65); OR 1.10 (1.05 to 1.15)). The main limitations of this analysis are that only the baseline results are presented, and there was an imbalance in invitations between the study arms. CONCLUSIONS: In this study, we observed that a real-life RHP of primary HPV-based screening was acceptable and effective when evaluated against cytology-based screening, as indicated by comparable participation, referral, and detection rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT01511328.

Early assessment of the first wave of the COVID-19 pandemic on cancer screening services: The International Cancer Screening Network COVID-19 survey.

Screening can decrease the burden of breast, cervical, and colorectal cancers. The COVID-19 pandemic led many countries to suspend cancer screening services as part of their response to the pandemic. The International Cancer Screening Network (ICSN) carried out an online survey to assess the effects of the first wave of the COVID-19 pandemic on cancer screening. A 33-item survey was distributed to 834 email addresses to gather information about settings and assess decision-making processes that led to cancer screening suspension. Information about communication, impact on resources, and patient follow-up was collected. Quantitative data was analyzed as frequencies overall and by setting, while a comment section under each survey item captured nuanced details. Responses were recategorized into 66 settings, representing 35 countries. Most settings suspended cancer screening services (n = 60, 90.9%) in March 2020 (n = 45, 68.2%), guided by a government decision (n = 51, 77.3%). Few settings made the decision whether to suspend services based on a preparedness plan (n = 17, 25.8%). In most settings, professionals were reassigned (n = 41, 62.1%) and infrastructure repurposed (n = 35, 53.0%). The first wave of the COVID-19 pandemic has had profound effects on cancer screening worldwide, including the suspension of services in almost all settings. Most settings were unprepared to deal with the scale of the pandemic but demonstrated flexibility in the response. These results contribute to inform, through experiences and lessons learned, the next steps for the global cancer screening community to further evaluate the impact of COVID-19 and prepare for future disruptions.

Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care.

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. Presence of IgG antibodies to SARS-CoV-2 was measured as an indicator of SARS-CoV-2 exposure. RESULTS: The total seroprevalence was 18% and increased during the study period. Among the seropositive HCWs, 11% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: adjusted odds ratio 1.96 (95% confidence intervals 1.59-2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the intensive care unit (also managing COVID-19 patients) was significantly lower. CONCLUSIONS: HCWs in contact with SARS-CoV-2 infected patients had a variable, but on average higher, likelihood for SARS-CoV-2 infections.

Elimination of HPV-associated oropharyngeal cancers in Nordic countries.

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 fertile-aged populations in the 1980's. The recent implementation of school-based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPV-associated OPSCC in the Nordic countries.

Antibodies to SARS-CoV-2 and risk of past or future sick leave.

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.

The cost-effectiveness of prostate cancer screening using the Stockholm3 test.

OBJECTIVES: The European Randomized Study of Screening for Prostate Cancer found that prostate-specific antigen (PSA) screening reduced prostate cancer mortality, however the costs and harms from screening may outweigh any mortality reduction. Compared with screening using the PSA test alone, using the Stockholm3 Model (S3M) as a reflex test for PSA ≥ 1 ng/mL has the same sensitivity for Gleason score ≥ 7 cancers while the relative positive fractions for Gleason score 6 cancers and no cancer were 0.83 and 0.56, respectively. The cost-effectiveness of the S3M test has not previously been assessed. METHODS: We undertook a cost-effectiveness analysis from a lifetime societal perspective. Using a microsimulation model, we simulated for: (i) no prostate cancer screening; (ii) screening using the PSA test; and (iii) screening using the S3M test as a reflex test for PSA values ≥ 1, 1.5 and 2 ng/mL. Screening strategies included quadrennial re-testing for ages 55-69 years performed by a general practitioner. Discounted costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Comparing S3M with a reflex threshold of 2 ng/mL with screening using the PSA test, S3M had increased effectiveness, reduced lifetime biopsies by 30%, and increased societal costs by 0.4%. Relative to the PSA test, the S3M reflex thresholds of 1, 1.5 and 2 ng/mL had ICERs of 170,000, 60,000 and 6,000 EUR/QALY, respectively. The S3M test was more cost-effective at higher biopsy costs. CONCLUSIONS: Prostate cancer screening using the S3M test for men with an initial PSA ≥ 2.0 ng/mL was cost-effective compared with screening using the PSA test alone.

High Amounts of SARS-CoV-2 Precede Sickness Among Asymptomatic Health Care Workers.

BACKGROUND: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity among asymptomatic subjects reflects past or future disease may be difficult to ascertain. METHODS: We tested 9449 employees at Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the results to sick leave records, and determined associations with past or future sick leave using multinomial logistic regression. RESULTS: Subjects with high amounts of SARS-CoV-2 virus, indicated by polymerase chain reaction (PCR) cycle threshold (Ct) value, had the highest risk for sick leave in the 2 weeks after testing (odds ratio [OR], 11.97; 95% confidence interval [CI], 6.29-22.80) whereas subjects with low amounts of virus had the highest risk for sick leave in the 3 weeks before testing (OR, 6.31; 95% CI, 4.38-9.08). Only 2.5% of employees were SARS-CoV-2 positive while 10.5% were positive by serology and 1.2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR, 1.06; 95% CI, .71-1.57). CONCLUSIONS: High amounts of SARS-CoV-2 virus, as determined using PCR Ct values, was associated with development of sickness in the next few weeks. Results support the concept that PCR Ct may be informative when testing for SARS-CoV-2. Clinical Trials Registration. NCT04411576.

A pilot study of risk-stratified cervical cancer screening.

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 different HPV types may vary in associated cancer risk by 100 times. Furthermore, HPV infections with the most oncogenic types are declining dramatically because of HPV vaccination programs. Tailoring screening intensity based on the known cancer risk of the individual (risk-stratified screening) therefore has great potential to increase both the sensitivity and specificity. Within Horizon 2020 a major project for Risk-stratified Screening for Cervical Cancer (RISCC) has therefore been launched. We performed a pilot study of risk-stratified screening to evaluate feasibility and acceptability of offering vaginal HPV self-sampling tests to women with a higher risk of cervical cancer. Methods: We identified resident women who had had either i) atypical glandular cells in screening tests during the past six years (risk >150/100,000 woman-years) or ii) abnormal screening findings above the age of 50, but without sufficient follow-up (risk >65/100,000). The women were invited, either by short message service (SMS) or physical letters, to order an HPV self-sampling kit via the study web-platform. The returned self-collected samples were tested for HPV. If positive, women were invited for clinical follow-up. Results: Among 920 targeted women, 191 (21%) placed an order and 163 (18%) returned a self-collected sample. Among all tested samples, 19 (12%) were positive for hrHPV and 18 of these women attended clinical follow-up. Conclusions: SMS invitations to high-risk women complemented with physical letters are feasible and result in substantial requests for kits and submission of samples. Future work will focus on improving the efficiency of the procedure and further increasing attendance.

HPV Vaccination and the Risk of Invasive Cervical Cancer.

BACKGROUND: The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. METHODS: We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history. RESULTS: During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. CONCLUSIONS: Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).

Long-Term Follow-Up of Men Invited to Participate in a Population-Based Abdominal Aortic Aneurysm Screening Program.

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 2010 to 2016 (n = 672) and a control group with normal aortas at screening (controls, n = 237). Medical charts and regional Swedvasc (Swedish Vascular registry) data were analyzed for aortic repair for men born 1945 to 1951. Ultrasound maximum aortic diameter (AD) as well as Aortic Size Index (ASI) was recorded. Participation was 78% and prevalence of AAA was 1.2% (n = 672). Aortic repair rates correlated with high ASI and AD. During the study period, 22% of the AAA patients were treated with the elective repair; 35 men in surveillance died (5.2%), non-AAA-related causes (82.9%) dominated, followed by unknown causes among 4 (11.4%), and 2 (5.7%) possibly AAA-related deaths. Abdominal aortic aneurysm rupture rate was higher among nonparticipants (0.096% vs 0.0036%, P < .001). The low dropout rate confirms acceptability of follow-up after screening. The efficacy is shown by the much higher rupture rate among the nonparticipating men.