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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 comprehensive human papillomavirus (HPV) genotyping. Methods and findings: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology bio-banks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases

BACKGROUND: Based on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule.METHODS: A population-based cohort of all women aged 13-30 years, living in Denmark or Sweden during 2006-2013, was followed for qHPV vaccination status and first occurrence of CIN2+.RESULTS: The study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13-16 and 17-19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11-0.49, and IRR = 0.65, 95% CI 0.41-1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13-16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses.CONCLUSIONS: Women vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.

Background: Russian suicide mortality rates changed rapidly over the second half of the twentieth century. This study attempts to differentiate between underlying period and cohort effects in relation to the changes in suicide mortality in Russia between 1956 and 2005. Methods: Sex-and age-specific suicide mortality data were analyzed using an age-period-cohort (APC) approach. Descriptive analyses and APC modeling with log-linear Poisson regression were performed. Results: Strong period effects were observed for the years during and after Gorbachev ' s political reforms (including the anti-alcohol campaign) and for those following the break-up of the Soviet Union. After mutual adjustment, the cohort-and period-specific relative risk estimates for suicide revealed differing underlying processes. While the estimated period effects had an overall positive trend, cohort-specific developments indicated a positive trend for the male cohorts born between 1891 and 1931 and for the female cohorts born between 1891 and 1911, but a negative trend for subsequent cohorts. Conclusions: Our results indicate that the specific life experiences of cohorts may be important for variations in suicide mortality across time, in addition to more immediate effects of changes in the social environment., The manuscript version of this article (Age, period and cohort effects on suicide mortality in Russia, 1956-2007) is part of the thesis Suicide in Russia: A macro-sociological study http://uu.diva-portal.org/smash/record.jsf?pid=diva2:608268

Objective: We provide an e-Science perspective on the workflow from risk factor discovery and classification of disease to evaluation of personalized intervention programs. As case studies, we use personalized prostate and breast cancer screenings. Materials and Methods: We describe an e-Science initiative in Sweden, e-Science for Cancer Prevention and Control (eCPC), which supports biomarker discovery and offers decision support for personalized intervention strategies. The generic eCPC contribution is a workflow with 4 nodes applied iteratively, and the concept of e-Science signifies systematic use of tools from the mathematical, statistical, data, and computer sciences. Results: The eCPC workflow is illustrated through 2 case studies. For prostate cancer, an in-house personalized screening tool, the Stockholm-3 model (S3M), is presented as an alternative to prostate-specific antigen testing alone. S3M is evaluated in a trial setting and plans for rollout in the population are discussed. For breast cancer, new biomarkers based on breast density and molecular profiles are developed and the US multicenter Women Informed to Screen Depending on Measures (WISDOM) trial is referred to for evaluation. While current eCPC data management uses a traditional data warehouse model, we discuss eCPC-developed features of a coherent data integration platform. Discussion and Conclusion: E-Science tools are a key part of an evidence-based process for personalized medicine. This paper provides a structured workflow from data and models to evaluation of new personalized intervention strategies. The importance of multidisciplinary collaboration is emphasized. Importantly, the generic concepts of the suggested eCPC workflow are transferrable to other disease domains, although each disease will require tailored solutions.

BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in 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: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period ( n = 2,466,671). Followup of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy ( incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined signi

Background: Genital chlamydia infection (chlamydia) is the most commonly reported sexually transmitted infection (STI) in Sweden. To guide prevention needs, we aimed to investigate factors associated with chlamydia. Methods: A cohort of visitors aged 20-40 years at an urban STI clinic in Sweden was recruited. Behavioural data were collected using a self-administered questionnaire. Self-sampled specimens were tested for chlamydia by a DNA amplification assay. Statistically significant (p<0.05) and epidemiologically relevant covariates were entered in a multivariate Poisson model adjusted for potential confounders (age and gender). Backward stepwise elimination produced a final model. Multiple imputation was used to account for missing values. Results: Out of 2814 respondents, 1436 were men with a chlamydia positivity rate of 12.6% vs 8.9% in women. Lifetime testing for chlamydia and HIV was high (82% and 60%, respectively). Factors significantly associated with chlamydia were: 20-24 years old (adjusted risk ratio (ARR)=2.10, 95% CI 1.21 to 3.65); testing reason: contact with a chlamydia case (ARR=6.55, 95% CI 4.77 to 8.98) and having symptoms (ARR=2.19, 95% CI 1.48 to 3.24); 6-10 sexual partners (ARR=1.53, 95% CI 1.06 to 2.21); last sexual activity 'vaginal sex and oral sex and anal sex and petting' (ARR=1.84, 95% CI 1.09 to 3.10); alcohol use before sex (ARR=1.98, 95% CI 1.10 to 3.57); men with symptoms (ARR=2.09, 95% CI 1.38 to 3.18); tested for chlamydia (ARR=0.72, 95% CI 0.55 to 0.94). Conclusions: Risk factors associated with chlamydia were consistent with previous reports in similar settings and suggest no major changes over time. Increased risk for chlamydia infection associated with high-risk behaviour (eg, alcohol use, increased number of sexual partners) supports the need for behavioural interventions in this population such as promotion of safer sex behaviour (condom use) and testing.

OBJECTIVES: To examine screening patterns and the risk of cervical neoplasia in women with rheumatoid arthritis (RA) treated or not with tumour necrosis factor inhibitors (TNFi). METHODS: We performed a nationwide register-based cohort study in Sweden of women with RA who started a first TNFi (n=9629), biologics-naive women with RA (n=34 984) and general population comparators (matched 1:10, n=300 331), followed up from 1999 to 2012. Outcomes were first cytology screening with normal outcome, first ever cervical intraepithelial neoplasia (CIN) grade 1, first ever CIN 2-3 or adenocarcinoma in situ and first ever invasive cervical cancer during follow-up. HRs were assessed through Cox regressions adjusted for age, educational level, prior cervical screens, comorbidities, marital status and prior hospitalisations. RESULTS: Biologic-naive women with RA had more screenings (HR 1.08, 95% CI 1.06 to 1.10), were at greater risk of CIN 1 (HR 1.53, 1.23 to 1.89) and CIN 2-3 (HR 1.39, 1.16 to 1.66), but not of invasive cervical cancer (HR 1.09, 0.71 to 1.65) compared with the general population. Patients who initiated TNFi therapy had similar screening patterns (HR 1.01, 0.98 to 1.05), were not at increased risk of CIN 1 (HR 1.23, 0.87 to 1.74), but were at increased risk of CIN 2-3 (HR 1.36, 1.01 to 1.82) and invasive cervical cancer (HR 2.10, 1.04 to 4.23) compared with biologics-naive women with RA. Estimates varied little with successive adjustments, but were attenuated/absent in sensitivity analyses restricted to 2006-2012 and a disease-modifying antirheumatic drugs-treated comparator. CONCLUSIONS: Women with RA in general are at elevated risk of cervical dysplasia. Compared with biologics-naive patients, women treated with TNFi are at increased risk of cervical cancer. Whether this increase is causally linked with TNFi could not be fully disentangled.

Background: Intra-generational social mobility, which describes the mobility within an individual’s own working life, is seldom studied among employees with psychiatric disorders (EPD). There is need of knowledge of the intra-generational mobility patterns, in a broader perspective, among EPD. Aims: To investigate intra-generational social mobility in employed individuals diagnosed with affective disorder, personality disorder, schizophrenia and drug dependence in a national Swedish cohort. Method: We identified a national sample of employed Swedish adults born in 1939–1949 (N = 876, 738), and among them individuals with a first-time hospital admission for affective psychosis, neurosis and personality disorder, alcoholism, drug dependence or schizophrenia in 1964–1980 (N = 18, 998). Employed individuals without hospital admission for such diagnoses were utilised as a comparison group (N = 866, 442). Intra-individual social class changes between 1980 and 1990 among EPD and the comparison group were described through summary statistics and graphs. Results: EPD more often held Low manual occupations at baseline in 1980 than the comparison group (44% vs. 28%), although parental social class was similar. In 1990, 19% of EPD and 4% of the comparison group had lost contact with the labour market. Social stability was less common among EPD (49 %) than in the comparison group (67%). Mobility out of the labour force increased and social stability decreased by number of inpatient admissions. Employees diagnosed with affective psychosis or neurosis and personality disorder fared better in the labour market than employees with schizophrenia. Conclusion: Employees suffering from psychiatric disorder do not maintain their social class or remain in the labour force to the same extent as individuals without those problems, irrespective of their parental class. Our results support the social drift hypothesis that individuals with poor psychiatric health move downward in the social hi

Grief over the loss of a family member may cause physical and mental illness, but an association between bereavement and cancer risk has not been established. Based on the Swedish National Cervical Screening Register (1969-2011) including 14,011,269 smears from 2,466,107 women, we conducted two nested case-control studies to examine the associations of bereavement (i.e., loss of a family member due to death) with abnormal cytology (390,310 first abnormal and 1,951,319 normal smears) and in situ/invasive cervical cancer (75,128 case and 375,640 control women), both individually matched on year of birth and screening adherence. Among 1,696 of the control women, we further investigated bereavement in association with HPV infection, both HPV16 and other HPV types. Bereavement was consistently associated with a 4-9% increased risk for first abnormal cytology, in situ and invasive cervical cancer (all P<0.02). The associations became stronger when multiple losses, loss of child, sibling or spouse, and loss due to unnatural cause were analyzed separately (P for trend or difference<0.0001), and for women with high screening adherence (P for difference<0.05). Among 1,696 women who had not developed cervical cancer, we further investigated the link between bereavement and HPV infection. Bereavement was associated with a 62% increased risk of HPV16 infection, high viral load, and recurrent infection, and was also more strongly associated with HPV infections designated as high-risk compared to low-risk determinants of cervical carcinogenesis. Collectively, our findings demonstrate that bereavement is associated with an increased risk of developing cervical cancer. Further, they suggest that this association may be attributed to stress-induced oncogenic HPV infections., Funding Agencies:NCI at the NIH 1R01CA093378-01A1 5R01CA111720-03Swedish National Cancer Society 4877-B03-01XAC 3436-B97-04XAAKarolinska InstitutetSwedish Society for Medical ResearchKarolinska Institutet Research Associate AwardKarolinska Institutet Distinguished Professor Award 2368/10-221