Cigarette Smoking Reduction and Health Risks: A Systematic Review and Meta-analysis.

INTRODUCTION: Studies have shown the health benefits of cigarette smoking cessation. However, the literature remains unclear about the relationship between smoking reduction and health risks. This comprehensive review and meta-analysis updates previous reviews with the newest estimates. AIMS AND METHODS: We conducted a systematic review and meta-analysis evaluating the association between smoking reduction and some health risks in observational studies. We defined the following smoking categories: heavy smokers smoked ≥15-20 cigarettes per day (CPD), moderate smokers smoked 10-19 CPD, and light smokers smoked <10 CPD. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effect models. RESULTS: We identified 19 studies including four case-control and 15 cohort studies. Compared with continuing heavy smokers, we found decreased lung cancer risk for those who reduced CPD by more than 50% (RR = 0.72, 95% CI: 0.52, 0.91), from heavy to moderate (RR = 0.66, 95% CI: 0.46, 0.85), and from heavy to light (RR = 0.60, 95% CI: 0.49, 0.72). We also found lower risk of cardiovascular disease (CVD) for those who reduced from heavy to light smoking (RR = 0.78, 95% CI: 0.67, 0.89) but not those who reduced by more than 50% and reduced smoking from heavy to moderate. We did not find any significant difference in all-cause mortality, all-cancer risks, and smoking-/tobacco-related cancer risk among those who reduced. CONCLUSIONS: Substantial smoking reduction may decrease lung cancer risk but results on CVD (coronary heart disease and stroke combined) risk were mixed. The relationships between smoking reduction and other endpoints examined were not significant. IMPLICATIONS: This meta-analysis helps clarify our understanding of various smoking reduction levels on some health risks. While smoking reduction may decrease risks of lung cancer, the relationships between smoking reduction and other endpoints, including all-cause mortality and cardiovascular disease, remain unclear. Although smoking reduction may decrease lung cancer risks, the magnitude of lung cancer risk remain high. Among smokers, complete cessation remains the most effective approach for cancer and CVD prevention.

e-Cigarette Use Among Youth in the United States, 2019.

Importance: The prevalence of e-cigarette use among US youth increased from 2011 to 2018. Continued monitoring of the prevalence of e-cigarette and other tobacco product use among youth is important to inform public health policy, planning, and regulatory efforts. Objective: To estimate the prevalence of e-cigarette use among US high school and middle school students in 2019 including frequency of use, brands used, and use of flavored products. Design, Setting, and Participants: Cross-sectional analyses of a school-based nationally representative sample of 19 018 US students in grades 6 to 12 participating in the 2019 National Youth Tobacco Survey. The survey was conducted from February 15, 2019, to May 24, 2019. Main Outcomes and Measures: Self-reported current (past 30-day) e-cigarette use estimates among high school and middle school students; frequent use (≥20 days in the past 30 days) and usual e-cigarette brand among current e-cigarette users; and use of flavored e-cigarettes and flavor types among current exclusive e-cigarette users (no use of other tobacco products) by school level and usual brand. Prevalence estimates were weighted to account for the complex sampling design. Results: The survey included 10 097 high school students (mean [SD] age, 16.1 [3.0] years; 47.5% female) and 8837 middle school students (mean [SD] age, 12.7 [2.8] years; 48.7% female). The response rate was 66.3%. An estimated 27.5% (95% CI, 25.3%-29.7%) of high school students and 10.5% (95% CI, 9.4%-11.8%) of middle school students reported current e-cigarette use. Among current e-cigarette users, an estimated 34.2% (95% CI, 31.2%-37.3%) of high school students and 18.0% (95% CI, 15.2%-21.2%) of middle school students reported frequent use, and an estimated 63.6% (95% CI, 59.3%-67.8%) of high school students and 65.4% (95% CI, 60.6%-69.9%) of middle school students reported exclusive use of e-cigarettes. Among current e-cigarette users, an estimated 59.1% (95% CI, 54.8%-63.2%) of high school students and 54.1% (95% CI, 49.1%-59.0%) of middle school students reported JUUL as their usual e-cigarette brand in the past 30 days; among current e-cigarette users, 13.8% (95% CI, 12.0%-15.9%) of high school students and 16.8% (95% CI, 13.6%-20.7%) of middle school students reported not having a usual e-cigarette brand. Among current exclusive e-cigarette users, an estimated 72.2% (95% CI, 69.1%-75.1%) of high school students and 59.2% (95% CI, 54.8%-63.4%) of middle school students used flavored e-cigarettes, with fruit, menthol or mint, and candy, desserts, or other sweets being the most commonly reported flavors. Conclusions and Relevance: In 2019, the prevalence of self-reported e-cigarette use was high among high school and middle school students, with many current e-cigarette users reporting frequent use and most of the exclusive e-cigarette users reporting use of flavored e-cigarettes.

Frequency of Use Among Middle and High School Student Tobacco Product Users - United States, 2015-2017.

Tobacco product use during adolescence increases the risk for lifelong nicotine addiction and immediate adverse health effects (1,2). During 2011-2017, current use of cigarettes, cigars, smokeless tobacco, and pipe tobacco decreased significantly among middle and high school students, but current use of e-cigarettes increased significantly from 1.5% to 11.7% (3). In 2017, an estimated 19.6% of high school students (2.95 million) and 5.6% of middle school students (0.67 million) were current users of any tobacco product; e-cigarettes were the most commonly used tobacco product for both middle (3.3%) and high (11.7%) school students (3). The Food and Drug Administration (FDA) and CDC analyzed combined data from the 2015-2017 National Youth Tobacco Surveys (NYTS) to determine past 30-day (current) frequency of use of cigarettes, e-cigarettes, cigars, smokeless tobacco, and hookahs among U.S. high school and middle school students. During 2015-2017, the proportion of students currently using tobacco products who used a product for ≥20 of the past 30 days ranged from 14.0% of cigar smokers to 38.7% of smokeless tobacco users among high school students and from 13.1% of e-cigarette users to 24.5% of hookah smokers among middle school students. Among current users, use of two or more tobacco products ranged from 76.7% (e-cigarettes) to 90.9% (hookahs) among those using the product ≥20 of the preceding 30 days, from 68.0% (e-cigarettes) to 84.2% (hookahs) among those using the product for 6 to 19 of the preceding 30 days, and from 48.8% (e-cigarettes) to 77.2% (cigarettes) among those using the product for 1 to 5 of the preceding 30 days. Sustained implementation of proven tobacco control strategies focusing on all types of tobacco products, in coordination with the regulation of tobacco products by FDA, are needed to reduce tobacco product initiation and use among U.S. youths.

Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES.

BACKGROUND: Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias. OBJECTIVE: We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES). DESIGN: Testosterone, oestradiol, sex hormone-binding globulin (SHBG), androstanediol glucuronide, and 25-hydroxyvitamin D (25(OH)D) were measured in serum from men aged 20 and older participating in NHANES III (n = 1315) and NHANES 2001-2004 (n = 318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4013 men from NHANES 2001-2006. RESULTS: In NHANES III, higher testosterone (quintile (Q) 1 = 17·2, 95% confidence interval (CI) = 16·1-18·6; Q5 = 19·6, 95% CI = 18·7-20·6 nmol/l, P-trend = 0·0002) and SHBG (Q1 = 33·8, 95% CI = 30·8-37·0; Q5 = 38·4, 95% CI = 35·8-41·2 nmol/l, P-trend = 0·0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001-2004. PSA concentration was not associated with serum 25(OH)D (P-trend = 0·34). CONCLUSION: Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk, and suggest the link to prostate cancer is not due to PSA-detection bias.

Inherited variation in the PARP1 gene and survival from melanoma.

We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p = 0.005, eleven cohorts) and MSS (HR = 1.20 per allele, 95% CI 1.01-1.39, p = 0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS.

Circadian pathway genes in relation to glioma risk and outcome.

PURPOSE: There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case-control study. METHODS: Subjects were genotyped for 17 candidate single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant, and recessive). Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 441 patients with high-grade tumors. Survival associations were validated using The Cancer Genome Atlas (TCGA) dataset. RESULTS: A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR 0.80; 95 % CI 0.66-0.97; p trend = 0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR 2.41; 95 % CI 1.31-4.42; p = 0.005), though not other glioma subtypes (p for heterogeneity = 0.0033). The association remained significant after false discovery rate adjustment (p = 0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in glioblastoma multiforme versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients. CONCLUSION: This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.

Reproductive factors and risk of primary brain tumors in women.

Gender-specific incidence patterns and the presence of hormonal receptors on tumor cells suggest that sex hormones may play a role in the onset of primary brain tumors. However, epidemiological studies on the relation of hormonal risk factors to the risk of brain tumors have been inconsistent. We examined the role of reproductive factors in the onset of glioma and meningioma in a case-control study conducted in the Southeastern US that included 507 glioma cases, 247 meningioma cases, and 695 community-based and friend controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) adjusting for age, race, US state of residence, and education. An older age at menarche was associated with an increased risk of glioma (≥ 15 vs. ≤ 12 years: OR 1.65; 95% CI 1.11-2.45), with a stronger association observed in pre-menopausal (OR 2.22; 95% CI 1.12-4.39) than post-menopausal (OR 1.55; 95% CI 0.93-2.58) women. When compared to controls, meningioma cases were more likely to have undergone natural menopause (OR 1.52; 95% CI 1.04-2.21) whereas glioma cases were less likely to be long term users of oral contraceptives (OR 0.47; 95% CI 0.33-0.68). Increasing parity was not related to the risk of either tumor. Current findings are consistent with a limited role for hormones in the onset of brain tumors in women. Results contribute to a growing body of evidence that a later age at menarche increases the risk of glioma in women.

Toenail iron, genetic determinants of iron status, and the risk of glioma.

PURPOSE: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case-control study. METHODS: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th-90th percentile, range: 10-44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. RESULTS: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 µg/g) vs. low (<6 µg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. CONCLUSION: The results do not support a role for body iron stores as a determinant of glioma risk.

Concordance of human papillomavirus types detected on the surface and in the tissue of genital lesions in men.

Swabbing the surface of a genital lesion to obtain a sample for HPV DNA testing is less invasive than a biopsy, but may not represent HPV types present in the lesion tissue. The objective of this study was to examine the concordance of HPV types detected in swab and biopsy samples from 165 genital lesions from men ages 18-70. Lesions included 90 condyloma, 10 penile intraepithelial neoplasia (PeIN), 23 non-condyloma with a known histology, and 42 lesions with an undetermined histology. All lesions were sampled by swabbing the surface of the lesion with a pre-wetted Dacron swab and taking a shave biopsy. HPV genotyping was performed using Linear Array for swab samples and INNO-LiPA for biopsy samples. The kappa and McNemar statistics were used to compare the concordance of detecting HPV types in swab and biopsy samples. Both sampling methods had high agreement for detection of HPV DNA in condyloma (87.8% agreement) and PeIN (100% agreement). There was also high concordance for detection of HPV16 (kappa = 1.00) and HPV18 (kappa = 1.00) in PeIN, however, agreement was low to moderate for detecting HPV6 (kappa = 0.31) and HPV11 (kappa = 0.56) in condyloma. Low to moderate agreement was also observed between sampling methods for detecting individual HPV types in the non-condyloma and lesions with an indefinite histology. The results suggest that obtaining a biopsy in addition to swabbing the surface of a lesion may provide additional information about specific HVP types associated with male genital lesions.

Early life exposures and the risk of adult glioma.

Exposure to common infections in early life may stimulate immune development and reduce the risk for developing cancer. Birth order and family size are proxies for the timing of exposure to childhood infections with several studies showing a reduced risk of glioma associated with a higher order of birth (and presumed younger age at infection). The aim of this study was to examine whether birth order, family size, and other early life exposures are associated with the risk of glioma in adults using data collected in a large clinic-based US case-control study including 889 glioma cases and 903 community controls. A structured interviewer-administered questionnaire was used to collect information on family structure, childhood exposures and other potential risk factors. Logistic regression was used to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between early life factors and glioma risk. Persons having any siblings were at significantly lower risk for glioma when compared to those reporting no siblings (OR=0.64; 95% CI 0.44-0.93; p=0.020). Compared to first-borns, individuals with older siblings had a significantly lower risk (OR=0.75; 95% CI 0.61-0.91; p=0.004). Birth weight, having been breast fed in infancy, and season of birth were not associated with glioma risk. The current findings lend further support to a growing body of evidence that early exposure to childhood infections reduces the risk of glioma onset in children and adults.

Risk factors for incident condyloma in a multinational cohort of men: the HIM study.

Identifying factors associated with condyloma are necessary for prevention efforts. Risk factors for incident condyloma were examined in a cohort of 2487 men from the United States, Brazil, and Mexico and were followed up every 6 months (median, 17.9 months). Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78-40.77]), age (HR, 0.43 [95% CI, .26-.77]; 45-70 vs 18-30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80-17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68-12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

Race and prevalence of human papillomavirus infection among men residing in Brazil, Mexico and the United States.

Human papillomavirus (HPV) causes anal, penile and oropharyngeal cancers in men. Genital HPV prevalence in men appears to vary by world region with men residing in Asia having among the lowest prevalence. Unfortunately, there is little information on prevalence of HPV infection in men by race. The purpose of this study was to examine HPV prevalence by race across three countries. 3,909 men ages 18-70 years enrolled in an ongoing prospective cohort study of the natural history of HPV in men (The HIM Study) were included in the analysis. Participants completed risk factor questionnaires and samples were taken from the penile epithelium and scrotum for HPV detection. HPV testing of the combined DNA extract was conducted using PCR and genotyping. Asian/Pacific Islanders had the lowest HPV prevalence of 42.2% compared to Blacks (66.2%), and Whites (71.5%). The Asian/Pacific Islander race was strongly protective in univariate analysis (prevalence ratio (PR) = 0.59; 95% confidence interval (CI): 0.48-0.74) and multivariate analysis for any HPV infection (PR = 0.65; 95% CI: 0.52-0.8). Stratified analysis by lifetime number of female partners also showed strong inverse associations with the Asian/Pacific Islander race. We consistently observed the lowest prevalence of HPV infection among Asian/Pacific Islanders with moderate inverse associations even after various adjustments for potential confounding factors. Unmeasured behavioral factors, sexual mixing with low risk women, and/or race-specific differences in the frequency of germline variations among immune regulating genes may underlie these associations. Further studies among Asian populations that incorporate measures of immuno-genetics are needed to understand this phenomenon.

Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study.

BACKGROUND: Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. METHODS: Men (aged 18-70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0-31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. FINDINGS: In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3-43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38-4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46-4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80-8·61) for any HPV and 12·19 months (7·16-18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31-0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56-0·91) and Mexico (0·73, 0·57-0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01-1·03). INTERPRETATION: The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. FUNDING: National Cancer Institute.

An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome.

PURPOSE: Experimental and epidemiological evidence shows a beneficial role of vitamin D in cancer. In vitro evidence is consistent with a similar protective function in glioma; however, no study has yet examined the potential role of vitamin D in glioma. METHODS: We evaluated the association between common genetic variants in the vitamin D pathway and glioma risk and patient outcome in 622 newly diagnosed glioma cases and 628 healthy controls enrolled in a clinic-based case-control study. Subjects were genotyped for 7 candidate and tagging single nucleotide polymorphisms in the vitamin D receptor and 8 additional variants in NADSYN1, GC, CYP24A1, CYP2R1, and C10ORF88 linked in genome-wide association studies to serum concentrations of vitamin D. Unconditional logistic regression was used to estimate age- and gender-adjusted odds ratios and 95 % confidence intervals for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 320 patients diagnosed with high-grade tumors. P values were uncorrected for multiple comparisons. RESULTS: Risk of astrocytic tumors was associated with variant alleles in rs3829251 (NADSYN1), rs10741657 (CYP2R1), rs2228570 (Fok1, VDR), and rs731236 (Taq1, VDR). No risk associations were found among oligodendroglial tumors. Survival associations were observed according to variant status for rs1544410 (Bsm1, VDR) and rs6013897 (CYP24A1). CONCLUSION: This exploratory analysis provides limited evidence of a role for genetic variation in vitamin D pathway genes with glioma risk and survival.

Incidence and human papillomavirus (HPV) type distribution of genital warts in a multinational cohort of men: the HPV in men study.

BACKGROUND: Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. METHODS: Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. RESULTS: Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%-21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). CONCLUSIONS: HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Electronic Nicotine Delivery System (ENDS) Device Types and Flavors Used by Youth in the PATH Study, 2016-2019.

The evolving electronic nicotine delivery system (ENDS) marketplace and recent regulatory actions may influence youth ENDS device preferences. Using data from Waves (W) 4, 4.5, and 5 (2016-2019) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study, this study estimated the prevalence of open and closed system primary ENDS use by youth (12-17 years) current (past 30-day) ENDS users, and compared demographics, tobacco use characteristics, and patterns of ENDS use, including flavors, by device type. Among current ENDS users, closed system use was significantly higher than open system use in W4.5 (68.3% vs. 31.7%) and W5 (60.5% vs. 39.5%). In W5, closed system users were more likely to have a regular ENDS brand, believe their ENDS had nicotine, and use tobacco and mint or menthol flavors in the past 30 days compared to open system users. In W5, users of closed systems were less likely to use fruit, non-alcoholic drink, and candy, desserts, or other sweets flavors in the past 30 days than users of open systems. Youth were more likely to use closed over open system ENDS in 2017-2019. Differences were observed between device types, particularly with flavor use, reflecting recent changes in flavored product availability.

Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013-2015.

Limited data are available for how biomarkers of tobacco exposure (BOE) change when cigarette smokers transition to using electronic nicotine delivery systems (ENDS). Using biomarker data from Waves 1 (2013-2014) and 2 (2014-2015) of the PATH Study, we examined how mean BOE concentrations, including metabolites of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC) and metals, changed when 2475 adult smokers transitioned to using ENDS or quit tobacco products. Exclusive smokers who transitioned to dual use had a significant decrease in NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), but not nicotine metabolites, most PAHs, metals, or VOCs. Exclusive smokers who became dual users had significant reductions in total nicotine equivalents, NNAL, and 2CyEMA (acrylonitrile metabolite), but only in those who reduced cigarettes per day (CPD) by >=50%. Smokers who transitioned to exclusive ENDS use had significant reductions in most TSNAs, PAHs, and VOCs; however, nicotine metabolites did not decrease in dual users who became exclusive ENDS users. Smokers who quit tobacco use had significant decreases in nicotine metabolites, all TSNAs, most PAHs, and most VOCs. Cigarette smokers who became dual users did not experience significant reductions in most BOEs. Reductions were impacted by changes in CPD. However, transitioning from smoking to no tobacco or exclusive ENDS use was associated with reduced exposure to most BOEs measured. Future analyses could incorporate additional waves of PATH data and examine changes in biomarker exposure by ENDS device type and CPD.

Genital HPV infection and related lesions in men.

Human papillomavirus (HPV) is highly prevalent in men and there is an interest in further understanding the relationship between HPV infection and disease in men, including the development of genital warts, penile intraepithelial neoplasia and invasive penile carcinomas. Genital warts are caused by HPV 6/11 and are the most common clinical manifestation of HPV in men. Though they are benign and not associated with mortality, they are a source of psychosocial distress and physical discomfort. HPV infection can also develop into invasive penile carcinoma which is associated with morbidity and mortality. Approximately 40% of invasive penile carcinomas are attributable to HPV with HPV 16, 18, and 6/11 being the genotypes most commonly detected in penile tumors. Penile carcinomas of the basaloid and warty histologic subtypes are most likely to test positive for HPV. In addition to HPV infection, the risk factors most strongly associated with penile cancer are lack of neonatal circumcision, phimosis (the inability of uncircumcised men to fully retract the foreskin), and anogenital warts. Male vaccination with the quadrivalent HPV vaccine that protects against HPV 6/11/16/18 has been shown to significantly reduce HPV-associated anogenital infection and disease in men. If the quadrivalent vaccine is successfully disseminated to large segments of the young male population, there is the potential for substantial reduction in genital HPV infection and related lesions in men.

Tobacco Product Use and Associated Factors Among Middle and High School Students - United States, 2019.

PROBLEM/CONDITION: Tobacco use is the leading cause of preventable disease, disability, and death in the United States. Most tobacco product use begins during adolescence. In recent years, tobacco products have evolved to include various smoked, smokeless, and electronic products. PERIOD COVERED: 2019. DESCRIPTION OF SYSTEM: The National Youth Tobacco Survey (NYTS) is an annual, cross-sectional, school-based, self-administered survey of U.S. middle school (grades 6-8) and high school (grades 9-12) students. A three-stage cluster sampling procedure is used to generate a nationally representative sample of U.S. students attending public and private schools. NYTS is the only nationally representative survey of U.S. middle and high school students that focuses exclusively on tobacco use patterns and associated factors. NYTS is designed to provide national data on tobacco product use and has been conducted periodically during 1999-2009 and annually since 2011. Data from NYTS are used to support the design, implementation, and evaluation of comprehensive tobacco use prevention and control programs and to inform tobacco regulatory activities. Since its inception in 1999 through 2018, NYTS had been conducted via paper and pencil questionnaires. In 2019, NYTS for the first time was administered in schools using electronic data collection methods. CDC's Office on Smoking and Health, in collaboration with the U.S. Food and Drug Administration's (FDA's) Center for Tobacco Products, analyzed data from the 2019 NYTS to assess tobacco product use patterns and associated factors among U.S. middle and high school students. Overall, 19,018 questionnaires were completed and weighted to represent approximately 27.0 million students. On the basis of self-reported grade level, this included 8,837 middle school questionnaires (11.9 million students) and 10,097 high school questionnaires (15.0 million students); 84 questionnaires with missing information on grade level were excluded from school-level analyses. RESULTS: In 2019, an estimated 53.3% of high school students (8.0 million) and 24.3% of middle school students (2.9 million) reported having ever tried a tobacco product. Current (past 30-day) use of a tobacco product (i.e., electronic cigarettes [e-cigarettes], cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis [small brown cigarettes wrapped in a leaf]) was reported by 31.2% of high school students (4.7 million) and 12.5% of middle school students (1.5 million). E-cigarettes were the most commonly cited tobacco product currently used by 27.5% of high school students (4.1 million) and 10.5% of middle school students (1.2 million), followed in order by cigars, cigarettes, smokeless tobacco, hookahs, and pipe tobacco. Tobacco product use also varied by sex and race/ethnicity. Among current users of each tobacco product, the prevalence of frequent tobacco product use (on ≥20 days of the preceding 30 days) ranged from 16.8% of cigar smokers to 34.1% of smokeless tobacco product users. Among current users of each individual tobacco product, e-cigarettes were the most commonly used flavored tobacco product (68.8% of current e-cigarette users). Among students who reported ever having tried e-cigarettes, the three most commonly selected reasons for use were "I was curious about them" (55.3%), "friend or family member used them" (30.8%), and "they are available in flavors, such as mint, candy, fruit, or chocolate" (22.4%). Among never users of each individual tobacco product, curiosity and susceptibility (a construct that can help to identify future tobacco product experimentation or use) was highest for e-cigarettes (39.1% and 45.0%, respectively) and cigarettes (37.0% and 45.9%, respectively). Overall, 86.3% of students who reported contact with an assessed potential source of tobacco product advertisements or promotions (going to a convenience store, supermarket, or gas station; using the Internet; watching television or streaming services or going to the movies; or reading newspapers or magazines) reported exposure to marketing for any tobacco product; 69.3% reported exposure to e-cigarette marketing and 81.7% reported exposure to marketing for cigarettes or other tobacco products. Among all students, perceiving no harm or little harm from intermittent tobacco product use (use on some days but not every day) was 28.2% for e-cigarettes, 16.4% for hookahs, 11.5% for smokeless tobacco products, and 9.5% for cigarettes. Among current users of any tobacco product, 24.7% reported experiencing cravings to use tobacco products during the past 30 days and 13.7% reported wanting to use a tobacco product within 30 minutes of waking. Moreover, 57.8% of current tobacco product users reported they were seriously thinking about quitting the use of all tobacco products and 57.5% reported they had stopped using all tobacco products for ≥1 day because they were trying to quit. INTERPRETATION: In 2019, approximately one in four youths (23.0%) had used a tobacco product during the past 30 days. By school level, this represented approximately three in 10 high school students (31.2%) and approximately one in eight middle school students (12.5%). Since 2014, e-cigarettes have been the most commonly used tobacco product among youths. Importantly, more than half of current youth tobacco product users reported seriously thinking about quitting all tobacco products in 2019. However, established factors of use and initiation, including the availability of flavors, exposure to tobacco product marketing, curiosity and susceptibility, and misperceptions about harm from tobacco product use, remained prevalent in 2019 and continue to promote tobacco product use among youths. PUBLIC HEALTH ACTION: The continued monitoring of all forms of youth tobacco product use and associated factors through surveillance efforts including NYTS is important to the development of public health policy and action at national, state, and community levels. Everyone, including public health professionals, health care providers, policymakers, educators, parents, and others who influence youths, can help protect youths from the harms of all tobacco products. In addition, the comprehensive and sustained implementation of evidence-based tobacco control strategies, combined with FDA's regulation of tobacco products, is important for reducing all forms of tobacco product use among U.S. youths.

Methylmercury exposure, genetic variation in metabolic enzymes, and the risk of glioma.

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 µg/g and 0.069 µg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 µg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.