Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

Using wastewater-based epidemiology as a potential instrument for the prediction and control of COVID-19 disease outbreaks.

The COVID-19 pandemic has revealed a significant number of cracks in the current vigilance techniques that stand to minimise outbreaks of SARS-CoV-2. There is a serious inadequacy of the testing capacity of healthcare systems worldwide, which can be attributed to the lack of appropriate testing and monitoring methods for a disease such as COVID-19. The current tools in use for COVID-19 surveillance are either expensive, not applicable to large populations or yield results after the outbreak has already occurred. The immense contagiousness in combination with a wealth of asymptomatic carriers means that RT-PCR testing is not feasible on a mass scale. It is evident that new methods are required for the monitoring of COVID-19 and a range of new epidemiological tools must be implemented if public health systems worldwide want to make relevant predictions on the patterns of disease spread and increase the efficacy of their decisions. In addition to this, the pandemic has highlighted the necessity for redirecting biomedical research towards early diagnosis and rational therapy of respiratory viruses in particular, as well as prevention of their spread by conventional means. An efficient early detection system would save lives and allow countries to return to pre-pandemic standards of living. At the forefront of this lies wastewater-based epidemiology, which carries immense potential as a means of pre-symptomatic diagnosis and population-based surveillance.

Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma.

The ccA and ccB molecular subtypes of clear cell renal cell carcinoma (ccRCC) have well-characterized prognostic relevance. However, it is not known whether they possess distinct etiologies. We investigated the relationships between these subtypes and RCC risk factors within a case-control study conducted in Eastern Europe. We analyzed risk factor data for ccA (n = 144) and ccB (n = 106) cases and 1476 controls through case-only and case-control comparisons to assess risk factor differences across subtypes using logistic and polytomous regression models. We also performed a meta-analysis summarizing case-only results from our study and three patient cohorts. Patients with ccB tumors had poorer survival than those with ccA tumors and were more likely to be male (case-only odds ratio [OR] 2.68, 95% confidence interval [CI] 1.43-5.03). In case-control analyses, body mass index was significantly associated with ccA tumors (OR 2.45, 95% CI 1.18-5.10 for ≥35 vs <25 kg/m2 ) but not with ccB tumors (1.52, 0.56-4.12), while trichloroethylene was associated with ccB but not ccA (OR 3.09, 95% CI 1.11-8.65 and 1.25, 0.36-4.39 respectively for ≥1.58 ppm-years vs unexposed). A polygenic risk score of genetic variants identified from genome-wide association studies was associated with both ccA and, in particular, ccB (OR 1.82, 1.11-2.99 and 2.87, 95% CI 1.64-5.01 respectively for 90th vs 10th percentile). In a meta-analysis of case-only results including three patient cohorts, we still observed the ccB excess for male sex and the ccA excess for obesity. In conclusion, our findings suggest the existence of etiologic heterogeneity across ccRCC molecular subtypes for several risk factors.

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

Oral health in a context of public health: prevention-related issue.

This publication analyses current literary knowledge on selected topics in the fields of oral health and pathology, with a particular emphasis on the potential roles of the oral microbiome and preventative approaches to oral afflictions. An important association with floral dysbiosis has been documented in important oral conditions, sometimes as a predisposing factor and at other times as a result thereof. However, much remains to be elucidated regarding the specific mechanisms at play, as well as their meaning in clinical practice. Continued research into the pathophysiology of certain oral diseases is of particular importance considering how widespread they are. A specific emphasis should be placed on understanding the exact mechanisms through which the microbiota facilitates health, and when disturbed, sickness. And perhaps of most importance is the implementation of knowledge already acquired on disease prevention if the burden of oral diseases worldwide is to decline in the future.

Principles of evidence-based medicine: from Robert Kochs postulates to a current EBM concept.

The aim of the article is to describe the development of the principles of medicine based on the evidence (EBM) based on postulates of Robert Koch, Nobel prize winner, protagonist of the "Golden Age" medical bacteriology, founder of a concept of modern microbiology and infectology. Kochs work led to the discovery of a causal relationship between exposure to a specific pathogen and disease on the example of identifying the cause of anthrax - Bacillus anthracis, a disease whose symptoms vary depending on the mode of transmission (gastrointestinal ingestion, cutaneous form on contact and pulmonary manifestations when inhaled). Tuberculosis caused by Kochs bacillus, Mycobacterium tuberculosis, yet still affecting 1.7 billion people (about 25 % of the world's population), in 95 % of cases in developing countries, where poverty and high prevalence of HIV are part of everyday life. Koch also discovered Vibrio cholerae, the pathogen responsible for seven recorded pandemics, and hitherto sporadic epidemics in recent years. The main contribution of the Kochs four postulates formulation was the principle, which helped to reveal the causal relationship between the pathogenic microbe to protrude infectious disease and obtain reliable evidence in improving credibility of diagnosis of infectious diseases. Other stages in the development of EBM were formulated by Bradford Hill in his nine principles, which are valid as well for noncommunicable diseases. The subjects of discussion are limitations and restrictions of present EBM and its essentials and the use in rational preventive, diagnostic and treatment strategies.

Health aspects of exposure to emissions from burning coal of high beryllium content: interactions with the immune system.

Beryllium has an impact on the human health of professionally or non-occupationally exposed people. Current evidence suggests that beryllium acts as a hapten with limited antigenic properties and is presented by antigen presenting cells to CD4+ T cells, which possess specific antigen receptors. The immunological changes in humoral immunoreactivity were considered biomarkers of beryllium exposure. In the present, due to the development of immunologic knowledge, tests of cellular immunity have promising potential for further research in this field. The historical view of the immune response to beryllium in acute and/or chronic beryllium disease is an example of the development of the interaction between mechanisms of innate and adaptive (specific), humoral and cellular immunity. The authors emphasize the increasing importance of immunological aspects in the studies of health impacts of human exposure to environmental pollutants.

Study design, size, and adequate exposure data as the crucial aspects in cancer risk assessment and implementation of the precautionary principle.

Traditional approaches and study design in cancer epidemiology have not been very successful in identifying and evaluating adequately the potential risk and/or protective factors associated with the disease. The main reasons for the failure are often due the small study sample size, and inadequate exposure information. In this paper, issues and approaches relevant to these two challenges are discussed. Multicentre study is proposed as a way to increase study size and to mitigate criticism about meta-analysis of independent studies. A multicentre study of large cohort or case-control studies also offer an exciting opportunity to study the contribution of epigenetic events that may be associated with lifestyle and environmental risk factors for human health. Optimizing methods for exposure assessment and how to reduce exposure to misclassification represent a difficult component in epidemiological studies. A potentially useful approach for improving exposure estimation is to rely on biomarkers of exposures. An example is provided to demonstrate how biomarkers of exposures could provide valuable information in addition to exposure measurements in traditional epidemiological studies. Finally, it is argued that risk assessment and the precautionary principle should not be viewed as conflicting paradigms but, rather, as a complementary approach for developing appropriate policies to address risks posed by exposure to carcinogens and a wide spectrum of other health hazards.

The presence of fine and ultrafine particulate matter in the work environment.

This study presents the results of pilot measurement, where the exposure of fine and ultrafine particulate matter was monitored. The measurement was performed in welding workplace, where these particles are produced unintentionally. The measurement consisted of collecting information and measuring the concentration of particles in the workplace, where data collection was focused only on inhalation exposure. During welding, primarily 300 nm size particles are produced, and their concentration is strongly influenced by the welding material, type of welding and suction. The particles are amorphous in terms of morphology and contain manganese, iron and silicon, which can cause neurodegenerative diseases. Furthermore, the results indicate the importance of monitoring oral exposure.

Risk of exposure to acrylamide.

OBJECTIVES: Acrylamide is a toxic compound that can be found it both occupational and non-occupational environments. This study focuses on its sources and health effects of its exposure. METHODS: Adverse effects of acrylamide, especially carcinogenic, genotoxic, and teratogenic were reported in many studies conducted on animals. Neurotoxicity was reported in workers exposed to acrylamide in the occupational environment. Another important source of populations' exposure to acrylamide is their nutrition. RESULTS: This study focuses on humans' exposure to acrylamide from various sources and its harmful effects on their health. CONCLUSIONS: Dietary intake of acrylamide, as well as occupational exposure, cigarette smoking, cosmetics usage and other environmental sources could have a significant effect on human health.

Occurrence of acrylamide in selected food products.

OBJECTIVE: Acrylamide is a toxic compound found in occupational and non-occupational environment. It originates from industrial use, technological processes in construction as well as food production, water purification, and laboratory use. Adverse effects including neurotoxicity, probably carcinogenicity, genotoxicity, teratogenicity, and reproductive toxicity were reported in many studies. Our study is focused on acrylamide content in selected food products in the Czech Republic. METHOD: In this study, we determined acrylamide content in selected samples of commonly consumed food products (potato chips, biscuits, popcorn, corn flakes, breakfast cereals, and baked muesli). RESULTS: The concentration of acrylamide in most samples of potato chips, biscuits and popcorn exceeded the benchmark limits. The acrylamide content in samples of potato chips from one manufacturer in 4 cases out of 5 analysed samples exceeded benchmark limit. On the other hand, no corn flakes sample acrylamide content from the same manufacture exceeded the benchmark limit. With 20 of all analysed samples exceeding the benchmark levels for acrylamide, it can be concluded that 47.6% of samples did not comply with the benchmark level. CONCLUSION: Dietary intake of frequently consumed food products with the acrylamide content exceeding the recommended comparative value could have adverse effects on the human health. Our study confirmed high amount of acrylamide in some selected food samples. The reduction of dietary burden with acrylamide is possible by complying with the correct technological principles in food preparation.

NATO and evidence-based military and disaster medicine: case for Vigorous Warrior Live Exercise Series.

The North Atlantic Treaty Organization (NATO) is the premier and only security alliance uniting 30 countries and growing with many partner states in the provision of collective security and against threats posed by conflict and natural disasters. Security of countries and communities is increasingly threatened by a broad spectrum of unconventional types of war and disease threats - from hybrid and asymmetric to multi-domain and peer-to-peer/near-peer conflict. The NATO Centre of Excellence for Military Medicine (MILMED COE) is the centre of gravity for medical best practices and promotion of medical doctrine across the NATO alliance. Disaster medicine is multidisciplinary and in NATO, multinational, requiring best practices that are driven by data and evidence to prevent death on the battlefield and prepare for future conflicts. "Vigorous Warrior" is a live military and disaster medicine exercise series using both civilian and military actors across all sectors of health focused on health security and identifying lessons learned to ready the alliance for future threats. In this brief report, we make the case that the Vigorous Warrior exercise exposes gaps, highlights challenges and generates an evidence base to make NATO military medicine systems more robust, more efficient and in provision of best medical practices. We specifically argue that clinical data capture must be duplicated and continuous across the alliance to ensure evidence-based medicine stays current in NATO military medical doctrine.

Psychosomatic and psychosocial aspects of health risks perception rising from living and occupational settings.

Psychosocial aspects may be of paramount importance in perceiving potential health risks. This is especially true when our knowledge of the real health implications of human exposure to the environmental risk factor is incomplete, or the intensity of this exposure is in the range of doubts as to possible biological effects. The most serious feature of these situations, particularly among psychologically labile individuals, is the presence of often severe neuropsychic and psychosomatic problems. Despite the difficult objectification, they pose different degrees of difficulty for the wearer to suffering, which cannot be underestimated in terms of the quality of their lives. Qualified assessment of potential health risks in the living and working environment, related to existing buildings and planned industrial, transport or other building activities/projects, is an essential part of their audit. While the initial phase of the risk assessment, namely its identification and exposure assessment, are of a purely natural nature, the self-estimation of the risk level already includes increasingly arbitrary aspects (e.g. safety factors). Risk communication and in particular risk management mean that, in the psychosocial terms, decision making is then put into a political context. The prevention of these problems can be systematic and timely educational or explanatory activity, targeted health education at the time of preparation of industrial, transport, military or other constructions and the use and involvement of local civic activists or activities. It does not have to be a cheap risk-shuffling but a clear convincing of the carrying capacity of the measure, with the advantages that the project will bring. Additional attempts to explain to the public the real state of affairs are usually accepted with distrust of hatred, with the information being “well-paid” misinformation that conceal the true state of affairs.

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

Added value of human biomonitoring in assessment of general population exposure to xenobiotics.

Human biomonitoring (HBM) has a wide range of applications and long tradition both in health care and the field of public health. Its major advantage is the integration of all exposure routes and sources. Since HBM information is an integrated exposure finding it offers the opportunity to trace and mimic a realistic exposure scenario. It reduces the number of assumptions that need to be made when estimating exposure and thus helps to reduce the uncertainties in exposure science. In spite of some challenges, such as further harmonization in the area of HBM, necessity of deriving equivalents of markers of external exposure and addressing the ethical and political aspects of its application, HBM is an efficient and cost-effective way to measure exposure levels of the human body to xenobiotics.

A horizontal transmission of genetic information and its importance for development of antibiotics resistance.

Genetic information is transmitted among organisms through two pathways - vertically from generation to generation (from parents to progeny) and horizontally (laterally) by direct exchange of genetic material across species barriers. These are primarily prokaryotes, in which the exchange of genes or whole gene segments by horizontal transmission is quite common. They can dynamically and in a relatively short time generate highly diverse genomes, which does not allow the vertical transmission. As a result, prokaryotes can rapidly acquire new properties such as virulence and pathogenicity as well as resistance to toxins, including antibiotics, by which they increase their adaptability. Therefore, reinfection-resistant microorganisms are always more difficult to treat than infections caused by non-resistant bacteria. Antibiotic resistance today is a global problem of health care service. Not only does the number of diseases caused by resistant pathogenic strains of bacteria increase, but also the cost of treatment increases disproportionately, the length of hospitalization is prolonged, and mortality is often rising. Therefore, when indicating antibiotic therapy, it is important to keep in mind that both overuse and abuse of antibiotics contribute to the spread of antibiotic resistance genes. This is equally true for antibiotic applications in veterinary medicine, agriculture, including aquacultures, or in the food industry. Keywords: horizontal transmission of genetic information, endosymbiosis, antibiotic resistance, risks of the emergence and spread of antibiotic resistance, prevention of antibiotic resistance.

Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

A systematic investigation of the contribution of genetic variation within the MHC region to HPV seropositivity.

High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.36-1.68, P = 1.0 × 10(-14)] and DRB1*1101 (OR = 1.89, 95%CI = 1.57-2.28, P = 1.5 × 10(-11)) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95%CI = 1.41-1.98, P = 2.6 × 10(-9)) and DQA1*0201 (OR = 1.67, 95%CI = 1.38-1.93, P = 1.7 × 10(-8)), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection.