Risk of Parkinson's Disease in Celiac Disease: A Swedish Population-Based Study.

Using a population-based matched cohort design, we assessed the association of celiac disease (CeD) with risk of PD by comparing patients with biopsy-confirmed CeD in Sweden to a biopsy-free population and their unaffected siblings, separately. No overall association was observed but CeD diagnosed before age 60 associated positively with incident diagnosis of PD (hazard ratio [HR] = 1.29; 95% confidence interval [CI]: 1.02-1.62), which was mainly attributed to the significantly elevated risk detected after 10-15 years since biopsy (HR = 1.68; 95% CI: 1.05-2.68). Our findings imply an increased vulnerability to long-term PD development among patients with CeD diagnosed before 60s. ANN NEUROL 2023;94:911-916.

Environmental risk factors for schizophrenia and bipolar disorder from childhood to diagnosis: a Swedish nested case-control study.

BACKGROUND: Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD. METHODS: We conducted a Swedish register-based nested case-control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988-2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence). RESULTS: All SUD types were associated with very high risk (IRR 4.9-25.5), and all forms of ACEs with higher risk (IRR 1.5-4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44-1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15-10.92; BD IRR 5.50, 5.15-5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17-1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03-1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13-1.35). CONCLUSIONS: There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

Advanced biological ageing predicts future risk for neurological diagnoses and clinical examination findings.

Age is a dominant risk factor for some of the most common neurological diseases. Biological ageing encompasses interindividual variation in the rate of ageing and can be calculated from clinical biomarkers or DNA methylation data amongst other approaches. Here, we tested the hypothesis that a biological age greater than one's chronological age affects the risk of future neurological diagnosis and the development of abnormal signs on clinical examination. We analysed data from the Swedish Adoption/Twin Study of Aging (SATSA): a cohort with 3175 assessments of 802 individuals followed-up over several decades. Six measures of biological ageing were generated: two physiological ages (created from bedside clinical measurements and standard blood tests) and four blood methylation age measures. Their effects on future stroke, dementia or Parkinson's disease diagnosis, or development of abnormal clinical signs, were determined using survival analysis, with and without stratification by twin pairs. Older physiological ages were associated with ischaemic stroke risk; for example one standard deviation advancement in baseline PhenoAgePhys or KDMAgePhys residual increased future ischaemic stroke risk by 29.2% [hazard ratio (HR): 1.29, 95% confidence interval (CI) 1.06-1.58, P = 0.012] and 42.9% (HR 1.43, CI 1.18-1.73, P = 3.1 × 10-4), respectively. In contrast, older methylation ages were more predictive of future dementia risk, which was increased by 29.7% (HR 1.30, CI 1.07-1.57, P = 0.007) per standard deviation advancement in HorvathAgeMeth. Older physiological ages were also positively associated with future development of abnormal patellar or pupillary reflexes, and the loss of normal gait. Measures of biological ageing can predict clinically relevant pathology of the nervous system independent of chronological age. This may help to explain variability in disease risk between individuals of the same age and strengthens the case for trials of geroprotective interventions for people with neurological disorders.

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.).

Novel disease associations with schizophrenia genetic risk revealed in ~400,000 UK Biobank participants.

Schizophrenia is a serious mental disorder with considerable somatic and psychiatric morbidity. It is unclear whether comorbid health conditions predominantly arise due to shared genetic risk or consequent to having schizophrenia. To explore the contribution of genetic risk for schizophrenia, we analysed the effect of schizophrenia polygenic risk scores (PRS) on a broad range of health problems in 406 929 individuals with no schizophrenia diagnosis from the UK Biobank. Diagnoses were derived from linked health data including primary care, hospital inpatient records, and registers with information on cancer and deaths. Schizophrenia PRS were generated and tested for associations with general health conditions, 16 ICD10 main chapters, and 603 diseases using linear and logistic regressions. Higher schizophrenia PRS was significantly associated with poorer overall health ratings, more hospital inpatient diagnoses, and more unique illnesses. It was also significantly positively associated with 4 ICD10 chapters: mental disorders; respiratory diseases; digestive diseases; and pregnancy, childbirth and the puerperium, but negatively associated with musculoskeletal disorders. Thirty-one specific phenotypes were significantly associated with schizophrenia PRS, and the 19 novel findings include several musculoskeletal diseases, respiratory diseases, digestive diseases, varicose veins, pituitary hyperfunction, and other peripheral nerve disorders. These findings extend knowledge of the pleiotropic effect of genetic risk for schizophrenia and offer insight into how some conditions often comorbid with schizophrenia arise. Additional studies incorporating the genetic basis of hormone regulation and involvement of immune mechanisms in the pathophysiology of schizophrenia may further elucidate the biological mechanisms underlying schizophrenia and its comorbid conditions.

Poor dental health and risk of pancreatic cancer: a nationwide registry-based cohort study in Sweden, 2009-2016.

BACKGROUND: Previous studies have reported inconsistent results regarding the association between poor dental health and pancreatic cancer risk. This study aimed to assess this association using a well-functioning nationwide dental health registry in Sweden. METHODS: Information of exposures (dental caries, root canal infection, mild inflammation, and periodontitis; the number of teeth) was ascertained from the Swedish Dental Health Register, and occurrence of pancreatic cancer was identified from both cancer and cause of death registries. Hazard ratios (HRs) were estimated using Cox models. RESULTS: During a median of 7.2 years of follow-up, 10,081 pancreatic cancers were identified among 5,889,441 individuals. Compared with the healthy status, a higher risk of pancreatic cancer was observed in individuals with root canal infection, mild inflammation, and periodontitis in the <50 age group (P for trend <0.001). In the 50-70 age group, only the subgroup with periodontitis had an excess risk (multivariable-adjusted HR = 1.20, 95% confidence interval [CI] 1.11-1.29). No positive association with statistical significance was observed in the 70+ age group. Individuals with fewer teeth tended to have a higher risk in all age groups. CONCLUSIONS: Our results confirmed the association between poor dental health and pancreatic cancer risk, which warrants further studies on underlying mechanisms.

Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: a Swedish National Register and Genomic Study.

A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.

Patterns of sexual behaviour associated with repeated chlamydia testing and infection in men and women: a latent class analysis.

BACKGROUND: Adolescents and young adults are at higher risk of acquiring Chlamydia trachomatis infection (chlamydia), so testing is promoted in these populations. Studies have shown that re-testing for chlamydia is common amongst them. We investigated how sexual risk behaviour profiles are associated with repeated testing for chlamydia. METHODS: We used baseline data from a cohort of 2814 individuals recruited at an urban STI -clinic. We applied latent class (LC) analysis using 9 manifest variables on sexual behaviour and substance use self-reported by the study participants. We fitted ordered logistic regression to investigate the association of LC membership with the outcomes repeated testing during the past 12 months and lifetime repeated testing for chlamydia. Models were fit separately for men and women. RESULTS: We identified four LCs for men and three LCs for women with increasing gradient of risky sexual behaviour. The two classes with the highest risk among men were associated with lifetime repeated testing for chlamydia: adjOR = 2.26 (95%CI: 1.50-3.40) and adjOR = 3.03 (95%CI: 1.93-4.74) as compared with the class with lowest risk. In women, the class with the highest risk was associated with increased odds of repeated lifetime testing (adjOR =1.85 (95%CI: 1.24-2.76)) and repeated testing during past 12 months (adjOR = 1.72 (95%CI: 1.16-2.54)). An association with chlamydia positive test at the time of the study and during the participant's lifetime was only found in the male highest risk classes. CONCLUSION: Prevention messages with regard to testing for chlamydia after unprotected sexual contact with new/casual partners seem to reach individuals in highest risk behaviour classes who are more likely to test repeatedly. Further prevention efforts should involve potentially more tailored sex-specific interventions taking into consideration risk behaviour patterns.

A principal component approach to improve association testing with polygenic risk scores.

Polygenic risk scores (PRSs) have become an increasingly popular approach for demonstrating polygenic influences on complex traits and for establishing common polygenic signals between different traits. PRSs are typically constructed using pruning and thresholding (P+T), but the best choice of parameters is uncertain; thus multiple settings are used and the best is chosen. Optimization can lead to inflated Type I error. Permutation procedures can correct this, but they can be computationally intensive. Alternatively, a single parameter setting can be chosen a priori for the PRS, but choosing suboptimal settings results in loss of power. We propose computing PRSs under a range of parameter settings, performing principal component analysis (PCA) on the resulting set of PRSs, and using the first PRS-PC in association tests. The first PC reweights the variants included in the PRS to achieve maximum variation over all PRS settings used. Using simulations and a real data application to study PRS association with bipolar disorder and psychosis in bipolar disorder, we compare the performance of the proposed PRS-PCA approach with a permutation test and an a priori selected p-value threshold. The PRS-PCA approach is simple to implement, outperforms the other strategies in most scenarios, and provides an unbiased estimate of prediction performance.

Plasma protein biomarkers for early detection of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, mainly due to late diagnosis at advanced tumor stages. In this study, we aimed to identify plasma protein biomarkers for early detection of PDAC. Totally, 135 PDAC patients (early PDAC, Stage I/II, n = 71; advanced PDAC, Stage III/IV, n = 64), 13 benign lesions/chronic pancreatitis patients and 72 healthy individuals, with corresponding plasma samples from a case-control study in Sweden were included. A proximity extension assay was used to detect 92 cancer-related proteins, and an enzyme-linked immunosorbent assay/electrochemiluminescence immunoassay was used to detect CA19-9. Predictive features were selected from these 93 candidate proteins and three covariates in the Swedish participants, and then validated in Spanish participants, including 37 early PDAC patients, 38 advanced PDAC patients, 19 chronic pancreatitis patients and 36 healthy controls. A panel of eight proteins discriminating early PDAC from healthy individuals was identified, and the cross-validated area under the curves (AUCs) were 0.85 (95% confidence interval, 95% CI, 0.78-0.91) and 0.81 (95% CI, 0.70-0.92) in the Swedish and Spanish participants, respectively. Another eight-protein panel was predictive for classifying advanced PDAC from healthy controls in two populations, with cross-validated AUCs of 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.83-0.98), respectively. In conclusion, eight protein biomarkers were identified and externally validated, potentially allowing early detection of PDAC patients if validated in additional prospective studies.

Changes in the Trend of Sexually Acquired Chlamydia Infections in Sweden and the Role of Testing: A Time Series Analysis.

BACKGROUND: We investigated the notification trends of sexually acquired chlamydia (chlamydia) and its association with testing in Sweden before (1992-2004) and after (2009-2018) the discovery of a new variant of Chlamydia trachomatis (nvCT). METHODS: We applied monthly time series analysis to study chlamydia trends and annual time series to study chlamydia rates adjusted for testing. We analyzed incidence nationally and by county group (based on able and unable to detect nvCT at time of discovery). RESULTS: We present data on 606,000 cases of chlamydia and 9.9 million persons tested. We found a U-shaped chlamydia trend during the period 1992-2004, with an overall increase of 83.7% from 1996 onward. The period 2009-2018 began with a stable trend at a high incidence level followed by a decrease of 19.7% during the period 2015-2018. Peaks were seen in autumn and through during winter and summer. Similar results were observed by groups of county, although with varying levels of increase and decrease in both periods. Furthermore, increased testing volume was associated with increased chlamydia rates during the first period (P = 0.019) but not the second period. CONCLUSIONS: Our results showed that chlamydia trends during the period 2009-2018 were not driven by testing, as they were during the period 1992-2004. This suggests less biased notified chlamydia rates and thus possibly a true decrease in chlamydia incidence rates. It is important to adjust case rates for testing intensity, and future research should target other potential factors influencing chlamydia rates.

Association Between Microscopic Colitis and Parkinson's Disease in a Swedish Population.

BACKGROUND: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD. OBJECTIVE: This study aimed to examine the association of MC with PD risk. METHODS: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (NMC /NSibling  = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12). CONCLUSIONS: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cervical cancer case-control audit: Results from routine evaluation of a nationwide cervical screening program.

Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.

Impact of HPV vaccination on cervical screening performance: a population-based cohort study.

BACKGROUND: Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology. METHODS: 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 histopathological diagnosis using Swedish National Cervical Screening Registry (NKCx). By linkage with the national Swedish HPV vaccination registry, we determined PPV of abnormal cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and the differences with 95% confidence intervals (CIs) according to vaccination status. RESULTS: The PPV of high-grade cytology for CIN2+ was 69.9% (95% CI, 67.9-71.9), 64.9% (95% CI, 59.8-69.8) and 57.4% (95% CI, 50.9-63.7) among women unvaccinated, initiating vaccination at age 17-22 years and initiating vaccination before age 17 years, corresponding to reduction in PPV by 8% (95% CI, 0-15%) and 17% (95% CI, 7-26%) in vaccinated groups after adjustment for birth cohort, respectively. CONCLUSION: The PPV of cytology for CIN2+ decreased among vaccinated women, and the decrease was stronger for girls vaccinated at younger ages. A switch from cytology to HPV testing might potentially improve the screening performance.

The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards: a large cohort study.

BACKGROUND: Frailty index (FI) is a well-established predictor of all-cause mortality, but less is known for cause-specific mortality and whether familial effects influence the associations. Middle-aged individuals are also understudied for the association between FI and mortality. Furthermore, the population mortality impact of frailty remains understudied. METHODS: We estimated the predictive value of FI for all-cause and cause-specific mortality, taking into account familial factors, and tested whether the associations are time-dependent. We also assessed the proportion of all-cause and cause-specific deaths that are attributable to increased levels of frailty. We analyzed 42,953 participants from the Screening Across the Lifespan Twin Study (aged 41-95 years at baseline) with up to 20 years' mortality follow-up. The FI was constructed using 44 health-related items. Deaths due to cardiovascular disease (CVD), respiratory-related causes, and cancer were considered in the cause-specific analysis. Generalized survival models were used in the analysis. RESULTS: Increased FI was associated with higher risks of all-cause, CVD, and respiratory-related mortality, with the corresponding hazard ratios of 1.28 (1.24, 1.32), 1.31 (1.23, 1.40), and 1.23 (1.11, 1.38) associated with a 10% increase in FI in male single responders, and 1.21 (1.18, 1.25), 1.27 (1.15, 1.34), and 1.26 (1.15, 1.39) in female single responders. No significant associations were observed for cancer mortality. No attenuation of the mortality associations in unrelated individuals was observed when adjusting for familial effects in twin pairs. The associations were time-dependent with relatively greater effects observed in younger ages. Before the age of 80, the proportions of deaths attributable to FI levels > 0.21 were 18.4% of all-cause deaths, 25.4% of CVD deaths, and 20.4% of respiratory-related deaths in men and 19.2% of all-cause deaths, 27.8% of CVD deaths, and 28.5% of respiratory-related deaths in women. After the age of 80, the attributable proportions decreased, most notably for all-cause and CVD mortality. CONCLUSIONS: Increased FI predicts higher risks of all-cause, CVD, and respiratory-related mortality independent of familial effects. Increased FI presents a relatively greater risk factor at midlife than in old age. Increased FI has a significant population mortality impact that is greatest through midlife until the age of 80.

Past and Recent Salted Fish and Preserved Food Intakes Are Weakly Associated with Nasopharyngeal Carcinoma Risk in Adults in Southern China.

BACKGROUND: Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent. OBJECTIVE: The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk. METHODS: We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression. RESULTS: We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97). CONCLUSIONS: Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought.

Mode of HPV vaccination delivery and equity in vaccine uptake: A nationwide cohort study.

Ten years after its introduction, equity in human papillomavirus (HPV) vaccine uptake remains unattained, not least for the groups at highest risk of cervical cancer. In Sweden, three different delivery modes of the vaccine have been in effect since May 2007. We used this as a natural experiment to investigate girls' HPV vaccine uptake in relation to parental country of birth and socioeconomic characteristics, by mode of delivery. Our nationwide study cohort comprised 689,676 girls born between 1990 and 2003. Data on HPV vaccination of the girls and parental birth/socioeconomic characteristics were retrieved from national registers. We examined the association between girls' vaccine uptake and parental characteristics, stratified by mode of delivery. The cumulative uptake of at least one dose of HPV vaccine was 37%, 48% and 79% for subsidised opportunistic, free-of-charge catch-up outside-school and free-of-charge school-based vaccination, respectively. In the subsidised vaccination, having parents born outside of Sweden, with low education and low family income was strongly associated with lower uptake [HR (95% confidence interval (CI)) = 0.49 (0.48-0.50), 0.32 (0.31-0.33), 0.53 (0.52-0.54), respectively]. The associations were partially reduced in catch-up outside-school, and strongly reduced in school-based vaccination delivery [HR (95% CI) =0.82 (0.81-0.83), 0.92 (0.91-0.94), 0.87 (0.85-0.88), respectively]. Free-of-charge school-based HPV vaccination achieved the highest uptake and displayed the least disparity in country of birth and socioeconomic background of the parents. This appears to be the most effective and equitable delivery mode for reaching high population vaccination coverage, including high-risk groups for cervical cancer.

Association between poor oral health and gastric cancer: A prospective cohort study.

Poor oral health may be involved in the pathogenesis of gastric cancer, however, some aspects have not been explored. Further, for previously studied aspects, for example, tooth-loss, the findings are inconsistent. We conducted a prospective cohort study of 19,831 participants from Uppsala, Sweden, cancer-free at baseline in 1973-1974 and followed until 2012 through linkage to national registers. We found that individuals with fewest teeth at baseline had an increased risk of gastric cancer relative to subjects with all examined teeth present (p = 1.75e-2). Presence of denture-associated lesions was also associated with an increased risk of gastric cancer (p = 1.00e-4). However, these excess risks significantly varied with attained age; estimated hazard ratio (HR) at attained age 50 for tooth loss was 4.24 [95% confidence interval (CI) 1.83-9.80] and 5.91 (95% CI 2.76-12.63) for denture-associated lesions, decreasing at an estimated 4% and 6% per year respectively, resulting in HR of 1.54 (95% CI 0.90-2.64) for tooth loss and HR 1.29 (95% CI 0.90-1.85) for denture-associated lesions at attained age 75. No increased risk of gastric cancer was found for individuals with higher levels of dental plaque, or with Candida-related or tongue lesions. In conclusion, tooth-loss and denture-associated lesions are associated with increased risks of gastric cancer. Previous conflicting findings of tooth-loss and gastric cancer risk may partly be explained by the age-varying relative risk of gastric cancer.

High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study.

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 biobanks 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, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.