• MeSH
• Delusions * diagnosis   etiology   therapy   MeSH
• Therapies, Investigational * methods   utilization   MeSH
• Cognitive Behavioral Therapy methods   trends   MeSH
• Humans MeSH
• Logic MeSH
• Memory physiology   MeSH
• Psychological Phenomena MeSH
• Psychotherapy methods   trends   MeSH
• Schizophrenia * therapy   MeSH
• Knowledge MeSH
• Check Tag
• Humans MeSH

• Keywords
• Dotazník hodnotící věrohodnost škály haklucinací,
• MeSH
• Behavioral Research MeSH
• Diagnosis, Differential MeSH
• Emotions classification   MeSH
• Expressed Emotion classification   MeSH
• Hallucinations * diagnosis   etiology   classification   MeSH
• Cognitive Behavioral Therapy * classification   methods   trends   MeSH
• Humans MeSH
• Perception classification   MeSH
• Surveys and Questionnaires MeSH
• Schizophrenia * diagnosis   therapy   MeSH
• Statistics as Topic MeSH
• Awareness classification   MeSH
• Consciousness classification   MeSH
• Check Tag
• Humans MeSH

• MeSH
• COVID-19 * MeSH
• Humans MeSH
• Nuclear Medicine * MeSH
• Pandemics MeSH
• SARS-CoV-2 MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

• MeSH
• Time Factors MeSH
• Adult MeSH
• Smoking adverse effects   epidemiology   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Head and Neck Neoplasms epidemiology   etiology   MeSH
• Laryngeal Neoplasms epidemiology   etiology   MeSH
• Oropharyngeal Neoplasms epidemiology   etiology   MeSH
• Mouth Neoplasms epidemiology   etiology   MeSH
• Alcohol Drinking adverse effects   epidemiology   pathology   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

• MeSH
• Adult MeSH
• Cigarette Smoking adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Head and Neck Neoplasms etiology   pathology   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

• MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Risk Assessment MeSH
• Polymorphism, Single Nucleotide * MeSH
• Smoking adverse effects   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Head and Neck Neoplasms genetics   MeSH
• Odds Ratio MeSH
• Alcohol Drinking adverse effects   epidemiology   MeSH
• BRCA2 Protein genetics   MeSH
• Risk Factors MeSH
• Aged MeSH
• Carcinoma, Squamous Cell genetics   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

• MeSH
• Early Detection of Cancer * MeSH
• Global Health MeSH
• HIV Seropositivity MeSH
• Papillomavirus Infections diagnosis   epidemiology   virology   MeSH
• Humans MeSH
• Human papillomavirus 16 isolation & purification   MeSH
• Anus Neoplasms diagnosis   virology   MeSH
• Uterine Cervical Neoplasms diagnosis   virology   MeSH
• Prevalence MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Systematic Review MeSH

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

• MeSH
• Demography MeSH
• Rad52 DNA Repair and Recombination Protein genetics   MeSH
• Physical Chromosome Mapping MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Loci * MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Chromosomes, Human, Pair 12 genetics   MeSH
• Quantitative Trait Loci genetics   MeSH
• Head and Neck Neoplasms genetics   MeSH
• Lung Neoplasms genetics   MeSH
• Computer Simulation MeSH
• Risk Factors MeSH
• Carcinoma, Squamous Cell genetics   MeSH
• Case-Control Studies MeSH
• Germ Cells MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

• MeSH
• Genome-Wide Association Study * MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Variation genetics   MeSH
• Genetic Markers genetics   MeSH
• Haplotypes genetics   MeSH
• HLA Antigens MeSH
• Papillomavirus Infections genetics   virology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Pharyngeal Neoplasms genetics   virology   MeSH
• Mouth Neoplasms genetics   virology   MeSH
• Papillomaviridae isolation & purification   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Mouth metabolism   pathology   virology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

BACKGROUND: Cigarette smoking is a major risk factor for head and neck cancer (HNC). To our knowledge, low cigarette smoking (<10 cigarettes per day) has not been extensively investigated in fine categories or among never alcohol drinkers. METHODS: We conducted a pooled analysis of individual participant data from 23 independent case-control studies including 19 660 HNC cases and 25 566 controls. After exclusion of subjects using other tobacco products including cigars, pipes, snuffed or chewed tobacco and straw cigarettes (tobacco product used in Brazil), as well as subjects smoking more than 10 cigarettes per day, 4093 HNC cases and 13 416 controls were included in the analysis. The lifetime average frequency of cigarette consumption was categorized as follows: never cigarette users, >0-3, >3-5, >5-10 cigarettes per day. RESULTS: Smoking >0-3 cigarettes per day was associated with a 50% increased risk of HNC in the study population [odds ratio (OR) = 1.52, 95% confidence interval (CI): (1.21, 1.90). Smoking >3-5 cigarettes per day was associated in each subgroup from OR = 2.01 (95% CI: 1.22, 3.31) among never alcohol drinkers to OR = 2.74 (95% CI: 2.01, 3.74) among women and in each cancer site, particularly laryngeal cancer (OR = 3.48, 95% CI: 2.40, 5.05). However, the observed increased risk of HNC for low smoking frequency was not found among smokers with smoking duration shorter than 20 years. CONCLUSION: Our results suggest a public health message that low frequency of cigarette consumption contributes to the development of HNC. However, smoking duration seems to play at least an equal or a stronger role in the development of HNC.

• MeSH
• Adult MeSH
• Cigarette Smoking epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Head and Neck Neoplasms epidemiology   MeSH
• Odds Ratio MeSH
• Alcohol Drinking epidemiology   MeSH
• Risk Factors MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Public Health MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH