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BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.
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Fator de Crescimento Insulin-Like I , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Pessoa de Meia-Idade , Estudos de Casos e Controles , Estudos Prospectivos , Europa (Continente)/epidemiologia , Idoso , Fatores de Risco , Biomarcadores Tumorais/sangue , Peptídeos Semelhantes à InsulinaRESUMO
INTRODUCTION: Contingency management (CM) is one of the most effective interventions for substance use disorders (SUDs), including stimulant use disorder. In the United States, the Veterans Health Administration (VHA) led the largest-scale rollout of CM in the US to date, but little is known about characteristics of patients treated and CM clinical practices. METHODS: In this retrospective cohort study, we used VHA electronic health records data to descriptively examine CM treatment course (e.g., number of visits, time between visits, duration of treatment episode) and characteristics of patients receiving CM for SUDs from 2018 to 2022. RESULTS: From January 2018 to September 2022, 2844 patients received CM at 90 VA Health Systems (including 98 VA Medical Center, 7 community-based outpatient clinics, and 15 other sites). The median number of CM visits was 8 (mean = 10.17, SD = 8.12) visits over the course of 1.5 months (median = 45 days, mean = 57.46 days, SD = 62.65). The target substance was stimulants in 86.42 % of visits. Average age of patients was 52.29 years (SD = 12.10), with 55.06 % of patients experiencing homelessness or housing instability, and 97.50 % of patients diagnosed with more than one SUD. Compared to the year prior to the COVID-19 pandemic (03/2019-02/2020; mean = 957.33, SD = 157.71 visits/month), CM visits declined by 83.20 % in the year following the pandemic (03/2020-02/2021; mean = 160.83, SD = 164.14), and have yet to return to pre-pandemic levels. CONCLUSIONS: The CM rollout has been markedly successful in the VHA, with adoption across multiple VHA sites within a complex patient population, indicating the potential for effective, more widespread CM implementation. At the same time, there was a considerable reduction in CM care during the COVID-19 pandemic and CM has not yet returned to pre-pandemic levels. Moreover, only a small minority of VA patients with stimulant use disorder have received CM. Given increasing rates of overdose, including stimulant-involved overdose, it is important to increase CM provision in VHA and non-VHA settings.
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Transtornos Relacionados ao Uso de Substâncias , United States Department of Veterans Affairs , Humanos , Estados Unidos/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , COVID-19/epidemiologia , Terapia Comportamental/métodos , Veteranos/estatística & dados numéricosRESUMO
BACKGROUND: There is a need to identify clinically meaningful non-abstinent endpoints for cocaine use disorder (CUD) clinical trials. In this study, we sought to replicate and extend prior work validating reductions in cocaine use frequency levels as an endpoint by examining associations between reductions in cocaine use frequency and long-term functioning outcomes. METHODS: We conducted a secondary analysis of two randomized clinical trials (N = 445; 77.5 % male; mean age = 42.18 years; 86.5 % Black, 10.8 % non-Hispanic white) that evaluated telephone-based continuing care for a 12- and 24-month period. Cocaine use frequency levels, measured with the Timeline Followback, were (1) abstinence (no past-month cocaine use), (2) low-frequency use (1-4 days of use/month), and (3) high-frequency use (5+ days of use/month). RESULTS: Among those who completed the 12-month follow-up (n = 392), most reduced from high-frequency use at baseline to abstinence at the 12-month follow-up (n = 243; 62.0 %). An additional 21.2 % (n = 83) reported either high-to-low-frequency use (n = 35; 8.9 %) or low use-to-abstinence (n = 48; 12.2 %); 16.8 % of participants (n = 66) did not change or increased their cocaine frequency level. Compared to those who had no change/increases in frequency levels, at least a one-level reduction from baseline to 12-month follow-up (i.e., high-to-low-frequency use, high-to-abstinence, low-to-abstinence) was concurrently associated with lower levels of negative consequences at the 12-month follow-up and prospectively with lower levels of cocaine use and consequences at 24-month follow-up, with effect sizes in the medium-to-large range. Those who reduced to abstinence generally had fewer drug use consequences at the 12-month follow-up than those who reduced to a low-frequency level; however, these groups did not significantly differ on any outcomes at the 24-month follow-up. CONCLUSIONS: Categorical reductions in cocaine use frequency levels, including those short of abstinence, are associated with less cocaine use and lower problem severity up to two years following treatment entry. Low-frequency cocaine use following the initial treatment phase does not appear to forebode worsening functioning, such as escalations in cocaine use.
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Transtornos Relacionados ao Uso de Cocaína , Humanos , Transtornos Relacionados ao Uso de Cocaína/terapia , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Masculino , Feminino , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Seguimentos , Fatores de Tempo , Telefone , Continuidade da Assistência ao PacienteRESUMO
Background: Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies. Polygenic risk scores (PRSs) are powerful tools for patient risk stratification but have not yet been widely used in primary care for lung cancer, particularly in diverse patient populations. Methods: We propose the GREAT care paradigm, which employs PRSs to stratify disease risk and personalize interventions. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardized PRS distributions across all ancestries. We applied our PRSs to 796 individuals from the GISC Trial, 350,154 from UK Biobank (UKBB), and 210,826 from All of Us Research Program (AoU), totaling 561,776 individuals of diverse ancestry. Results: Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58 - 2.18) in UKBB and 2.39 (95% CI: 1.93 - 2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32 - 1.41) in UKBB and 1.32 (95% CI: 1.28 - 1.36) in AoU. Conclusion: Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations. This model will be evaluated in two cluster-randomized clinical trials aimed at motivating health behavior changes in high-risk patients of diverse ancestry. This pioneering approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment.
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Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
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Neoplasias , Humanos , Neoplasias/genética , Feminino , Fatores de Risco , Análise da Randomização Mendeliana , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/sangue , Masculino , Proteínas Sanguíneas/metabolismoRESUMO
The COVID pandemic placed a spotlight on alcohol use and the hardships of working within the food and beverage industry, with millions left jobless. Following previous studies that have found elevated rates of alcohol problems among bartenders and servers, here we studied the alcohol use of bartenders and servers who were employed during COVID. From February 12-June 16, 2021, in the midst of the U.S. COVID national emergency declaration, survey data from 1,010 employed bartender and servers were analyzed to quantify rates of excessive or hazardous drinking along with regression predictors of alcohol use as assessed by the 10-item Alcohol Use Disorders Identification Test (AUDIT). Findings indicate that more than 2 out of 5 (44%) people surveyed reported moderate or high rates of alcohol problem severity (i.e., AUDIT scores of 8 or higher)-a rate 4 to 6 times that of the heavy alcohol use rate reported pre- or mid-pandemic by adults within and outside the industry. Person-level factors (gender, substance use, mood) along with the drinking habits of one's core social group were significantly associated with alcohol use. Bartenders and servers reported surprisingly high rates of alcohol problem severity and experienced risk factors for hazardous drinking at multiple ecological levels. Being a highly vulnerable and understudied population, more studies on bartenders and servers are needed to assess and manage the true toll of alcohol consumption for industry employees.
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Transtornos Relacionados ao Uso de Álcool , Alcoolismo , COVID-19 , Adulto , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , COVID-19/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Stimulant-related overdoses have increased dramatically, with almost 50% of overdoses in the United States now involving stimulants. Additionally, harm-reduction approaches are increasingly seen as key to reducing the negative impact of substance use. Contingency management (CM), the provision of financial incentives for abstinence, is the most effective treatment for stimulant use disorder, but historically has not been widely implemented. Many recent, large-scale implementation efforts have relied upon foundational CM protocols that may not sufficiently account for recent increases in the prevalence and lethality of stimulant use nor the growing preference for harm reduction versus abstinence-only frameworks. ARGUMENT: We argue the need to (1) consider whether and how CM protocols might be modified to address rising stimulant use and harm reduction frameworks and (2) make CM widely accessible so that it can reduce population-level stimulant use while ensuring that it is delivered with fidelity to its basic principles. Proposed changes include changing CM reinforcement schedules to emphasize treatment engagement and reductions in use in addition to abstinence, changing guidelines on the duration of and re-engagement in CM, investing in research on virtual CM, incentivizing providers and health systems to deliver CM, making it easier to purchase and use point-of-care drug screens, using direct-to-consumer marketing to increase demand for CM and adapting CM to the community in which it is being implemented. CONCLUSIONS: Our proposed modifications to contingency management (CM) protocols and accessibility may more effectively address rising stimulant use and align CM more closely with harm-reduction frameworks. Given the urgent need to reduce overdose deaths, developing and testing modified CM protocols may need to rely upon methods other than randomized controlled trials. Efforts to disseminate CM widely to reduce population-level stimulant use must be balanced with the need to maintain fidelity to CM's basic principles.
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Terapia Comportamental , Estimulantes do Sistema Nervoso Central , Overdose de Drogas , Redução do Dano , Transtornos Relacionados ao Uso de Substâncias , Humanos , Overdose de Drogas/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Terapia Comportamental/métodos , Estados Unidos , MotivaçãoRESUMO
Background: At-risk alcohol use is associated with increased adverse health consequences, yet is undertreated in healthcare settings. People residing in rural areas need improved access to services; however, few interventions are designed to meet the needs of rural populations. Mobile interventions can provide feasible, low-cost, and scalable means for reaching this population and improving health, and behavioral economic approaches are promising. Methods: We conducted a pilot randomized controlled trial focused on acceptability and feasibility of a mobile behavioral economic intervention for 75 rural-residing adults with at-risk alcohol use. We recruited participants from a large healthcare system and randomized them to one of four virtually-delivered conditions reflecting behavioral economic approaches: episodic future thinking (EFT), volitional choice (VC), both EFT and VC, or enhanced usual care control (EUC). The intervention included a telephone-delivered induction session followed by two weeks of condition-consistent ecological momentary interventions (EMIs; 2x/day) and ecological momentary assessments (EMAs; 1x/day). Participants completed assessments at baseline, post-intervention, and two-month follow-up, and provided intervention feedback. Results: All participants completed the telephone-delivered session and elected to receive EMI messages. Average completion rate of EMAs across conditions was 92.9%. Among participants in active intervention conditions, 89.3% reported the induction session was helpful and 80.0% reported it influenced their future drinking. We also report initial alcohol use outcomes. Discussion: The behavioral economic intervention components and trial procedures evaluated here appear to be feasible and acceptable. Next steps include determination of their efficacy to reduce alcohol use and public health harms.
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OBJECTIVE: Understanding the causal mechanisms through which telephone and mobile health continuing care approaches reduce alcohol use can help develop more efficient interventions that effectively target these mechanisms. Self-efficacy for successfully coping with high-risk alcohol relapse situations is a theoretically and empirically supported mediator of alcohol treatment. This secondary analysis aims to examine self-efficacy as a mechanism through which remote-delivered continuing care interventions reduce alcohol use. METHOD: The study included 262 adults (Mage = 46.9, SD = 7.4) who had completed 3 weeks of an intensive outpatient alcohol treatment program. The sample was predominantly male (71%), African American (82%), and completed a high school education (71%). The four-arm randomized clinical trial compared three active continuing care interventions (telephone monitoring and counseling [TMC], addiction comprehensive health enhancement support system [ACHESS], and combined delivery of TMC and ACHESS) to usual care and assessed longitudinal measures of alcohol use and self-efficacy. Analyses employed the potential outcomes framework and sensitivity analyses to address threats to causal inference resulting from an observed mediator variable. RESULTS: Relative to usual care, the two intervention conditions that included TMC reduced alcohol use through improvements to self-efficacy. There was no evidence that self-efficacy mediated the effect of ACHESS on alcohol use. CONCLUSIONS: Based on our findings, self-efficacy is an important mechanism through which telephone continuing care interventions affect alcohol use. Future research to identify which components of TMC influence self-efficacy and factors that mediate ACHESS effects could enhance the effectiveness of remote delivery of continuing care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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BACKGROUND: Unhealthy alcohol consumption is a severe public health problem. But low to moderate alcohol consumption is associated with high subjective well-being, possibly because alcohol is commonly consumed socially together with friends, who often are important for subjective well-being. Disentangling the health and social complexities of alcohol behavior has been difficult using traditional rating scales with cross-section designs. We aim to better understand these complexities by examining individuals' everyday affective subjective well-being language, in addition to rating scales, and via both between- and within-person designs across multiple weeks. METHOD: We used daily language and ecological momentary assessment on 908 US restaurant workers (12692 days) over two-week intervals. Participants were asked up to three times a day to "describe your current feelings", rate their emotions, and report their alcohol behavior in the past 24 hours, including if they were drinking alone or with others. RESULTS: Both between and within individuals, language-based subjective well-being predicted alcohol behavior more accurately than corresponding rating scales. Individuals self-reported being happier on days when drinking more, with language characteristic of these days predominantly describing socializing with friends. Between individuals (over several weeks), subjective well-being correlated much more negatively with drinking alone (r = -.29) than it did with total drinking (r = -.10). Aligned with this, people who drank more alone generally described their feelings as sad, stressed and anxious and drinking alone days related to nervous and annoyed language as well as a lower reported subjective well-being. CONCLUSIONS: Individuals' daily subjective well-being, as measured via language, in part, explained the social aspects of alcohol drinking. Further, being alone explained this relationship, such that drinking alone was associated with lower subjective well-being.
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Avaliação Momentânea Ecológica , Etanol , Humanos , Consumo de Bebidas Alcoólicas , Idioma , AutorrelatoRESUMO
BACKGROUND: The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fail. In other fields such as depression, brief measures to address these tasks combined with an action plan-so-called measurement-based care (MBC)-have been associated with better outcomes. This workgroup aimed to determine whether brief measures can be identified for using MBC for optimizing dosing or informing treatment decisions in OUD. METHODS: The National Institute on Drug Abuse Center for the Clinical Trials Network (NIDA CCTN) in 2022 convened a small workgroup to develop consensus about clinically usable measures to improve the quality of treatment delivery with MBC methods for OUD. Two clinical tasks were addressed: (1) to identify the optimal dose of medications for OUD for each patient and (2) to estimate the effectiveness of a treatment for a particular patient once implemented, in a more granular fashion than the binary categories of early or sustained remission or no remission found in The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). DISCUSSION: Five parameters were recommended to personalize medication dose adjustment: withdrawal symptoms, opioid use, magnitude (severity and duration) of the subjective effects when opioids are used, craving, and side effects. A brief rating of each OUD-specific parameter to adjust dosing and a global assessment or verbal question for side-effects was viewed as sufficient. Whether these ratings produce better outcomes (e.g., treatment engagement and retention) in practice deserves study. There was consensus that core signs and symptoms of OUD based on some of the 5 DSM-5 domains (e.g., craving, withdrawal) should be the basis for assessing treatment outcome. No existing brief measure was found to meet all the consensus recommendations. Next steps would be to select, adapt or develop de novo items/brief scales to inform clinical decision-making about dose and treatment effectiveness. Psychometric testing, assessment of acceptability and whether the use of such scales produces better symptom control, quality of life (QoL), daily function or better prognosis as compared to treatment as usual deserves investigation.
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Transtornos Relacionados ao Uso de Opioides , Qualidade de Vida , Humanos , Consenso , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Analgésicos Opioides/uso terapêutico , Tratamento de Substituição de Opiáceos/métodosRESUMO
BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. RESULTS: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12-3.50, P-value = 4.13 × 10-15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99-2.49, P-value = 5.70 × 10-46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72-0.74). CONCLUSIONS: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.
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Estratificação de Risco Genético , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Teorema de Bayes , Estudo de Associação Genômica Ampla , Incerteza , Medição de Risco , Fatores de Risco , Predisposição Genética para DoençaRESUMO
BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Fumantes , Estudo de Associação Genômica Ampla , Projetos de Pesquisa , Fumar/efeitos adversosRESUMO
A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Papillomavirus Humano 16 , Papillomavirus Humano , Neoplasias de Cabeça e Pescoço/diagnósticoRESUMO
BACKGROUND: People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. METHODS: We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers. RESULTS: We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship. CONCLUSIONS: These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms.