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Objective: Multiple organizations recommend an annual digital anal rectal examination (DARE) for people at highest risk for anal cancer. The authors assessed DARE usage among sexual minority men and transgender women., Methods: Community-recruited and asymptomatic individuals from a mid-sized US city were enrolled into the Prevent Anal Cancer Self-Swab Study, a longitudinal clinical trial of anal cancer screening. Self-reported data from the baseline survey were used to assess usage of DARE in the last year and during the lifetime. Adjusted odds ratios (aORs) and CIs for factors associated with each outcome were determined using multivariable logistic regression., Results: Among 241 participants, median age was 46 years (interquartile range, 33-57 years), 27.0% were living with HIV, and 24.5% reported a previous diagnosis of anal warts. A total of 13.7% (95% CI = 9.4%-18.0%) of individuals reported a DARE in the previous year, whereas 53.9% (95% CI = 47.7%-60.2%) reported a DARE during the lifetime. The following were associated with a DARE in the previous year: increasing age (aOR = 1.04; 95% CI = 1.01-1.08 for each additional year), any previous anal cytology (aOR = 2.62; 95% CI = 1.19-5.80, compared with no previous test or no knowledge of a test), and preferred receptive position during anal sex (aOR = 4.93; 95% CI = 1.17-20.86 compared with insertive)., Conclusions: Despite guidelines recommending an annual DARE, it was uncommonly reported. There is an urgent need to understand barriers to conducting DARE among individuals most vulnerable to anal cancer and their health care providers., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

The human papillomavirus (HPV) vaccine is the most expensive of all routinely recommended pediatric vaccines. Adequate cost reimbursement by 3rd-party payers is a critical enabling factor for clinicians to continue offering vaccines. This study found that net returns from HPV vaccine cost reimbursements are lowest for family physicians ($0.34/dose) and highest for pediatricians ($5.08/dose). Furthermore, a $1 increment in return was associated with an increase in HPV vaccine doses administered (highest for family physicians; 0.08% per dollar). Reimbursement for HPV vaccine costs by private payers is adequate; however, return margins are small for non-pediatric specialties., (© 2023 Annals of Family Medicine, Inc.)

Background and Objective: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors improve progression-free survival when combined with endocrine therapies in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. However, the comparative cost effectiveness of utilizing three US Food and Drug Administration-approved CDK4/6 inhibitors is unknown. Therefore, we aimed to evaluate the cost effectiveness of individual CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) with letrozole versus letrozole monotherapy in the first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in the USA., Methods: We constructed a Markov-based decision-analytic model to evaluate the cost effectiveness of CDK4/6 inhibitors plus endocrine therapies over a 40-year lifetime from a third-party payer perspective. The model incorporated health states (progression-free disease, progressive disease, and death), major adverse events (neutropenia), and cancer-specific and all-cause mortality. Using clinical efficacy and quality-of-life scores (utility) data from clinical trials, we estimated quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios using Medicare charges reported in US dollars per 2022 valuation and a discount rate of 3% applied to costs and outcomes. We performed deterministic and probabilistic sensitivity analyses to evaluate parametric and decision uncertainty., Results: Compared to letrozole, the model estimated an increase of 5.72, 5.87, and 6.39 in QALYs and costs of $799,178, $788,168, and $741,102 in combining palbociclib, ribociclib, and abemaciclib plus letrozole, respectively. Palbociclib or ribociclib plus letrozole were dominated by abemaciclib plus letrozole. Compared with letrozole, abemaciclib plus letrozole resulted in an incremental cost-effectiveness ratio of $457,538 per QALY with an incremental cost of $553,621 and an incremental QALY gain of 1.21. The results were sensitive to the cost of abemaciclib, disease progression utility, and patients' age., Conclusions: At a willingness to pay of $100,000/QALY gained, our model predicts that combining CDK4/6 inhibitors plus letrozole is not cost effective with a marginal increase in QALYs at a high cost. Lowering the cost of these drugs or identifying patients who can receive maximal benefit from CDK4/6 inhibitors would improve the value of this regimen in patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Home-based self-sampling for human papillomavirus (HPV) testing may be an alternative for women not attending clinic-based cervical cancer screening., Methods: We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women aged 30-65 and under-screened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups, and determined statistical significance at p<0.05., Results: Over half of 233 survey participants reported that clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The last two factors were significantly more prevalent among Spanish vs English speakers (66.4% vs 30% (p=0.000) and 69.9 vs 52.2% (p=0.006), respectively). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%), and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish vs English speakers (79.6% vs 53.38%, p=0.001) and among patients with elementary education or below., Conclusions: The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments, and ease of using kits. HPV self-sampling kits may reduce barriers among under-screened women in a safety-net system., Funding: This study is supported by a grant from the National Institute for Minority Health and Health Disparitie s (NIMHD, R01MD013715, PI: JR Montealegre)., Clinical Trial Number: NCT03898167., Competing Interests: SP, AD, BC, DL, MD, SV, JM No competing interests declared, (© 2023, Parker et al.)

Background: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that treat early rectal cancer (ERC). Both are effective treatments, yet there are very few studies comparing them. The aim of our study was to identify ideal candidates for each procedure., Materials and Methods: Between January 2016 and November 2019, 204 ERC patients were managed with either ESD (n=101) or TEM (n=103) at 7 international centers. Data analyzed included clinical success, tumor characteristics, procedure info, and recurrence rates., Results: Median tumor size was 40 mm±23.9 in the ESD group and 56 mm±27.9 in the TEM group, significantly larger in the latter ( P <0.00001). Average procedure time was 131.5±67.9 minutes in ESD group and 104.9±28.4 minutes in TEM group ( P =0.000347). Average hospital stay was 3.3±2.6 days in the ESD group and 4.7±0.7 days in the TEM group ( P <0.00001). Adverse event rate was 6.8% in the ESD group and 24% in the TEM group. There were no significant difference in the rate of en bloc resection, technical success, tumor location, necessity of additional procedures, and tumor recurrence rates., Conclusion: Compared with TEM, ESD is a safer procedure with shorter hospital stay and should be offered for patients who have ERC., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues., Methods: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance system) prevalence were evaluated using Spearman's rank correlation coefficient., Results: Nationally, SCCA incidence and mortality rates (per 100,000) increased among men (incidence, 2.29-3.36, mortality, 0.46-0.74) and women (incidence, 3.88-6.30, mortality, 0.65-1.02) age ≥ 50 years, but decreased among men age < 50 years and were stable among similar-aged women. In state-level analysis, a marked increase in incidence (≥ 1.5-fold for men and ≥ two-fold for women) and mortality (≥ two-fold) for persons age ≥ 50 years was largely concentrated in the Midwestern and Southeastern states. State-level SCCA incidence rates in recent years (2014-2018) among men were correlated ( r = 0.47, P < .001) with state-level AIDS prevalence patterns. For women, a correlation was observed between state-level SCCA incidence rates and smoking prevalence ( r = 0.49, P < .001)., Conclusion: During 2001-2005 to 2014-2018, SCCA incidence and mortality nearly doubled among men and women age ≥ 50 years living in Midwest and Southeast. State variation in AIDS and smoking patterns may explain variation in SCCA incidence. Improved and targeted prevention is needed to combat the rise in SCCA incidence and mitigate magnifying geographic disparities.

Squamous cell carcinoma of the anus (SCCA) is caused by HPV, and is elevated in persons living with HIV (PLWHIV). We aimed to estimate sex- and HIV-stratified SCCA burden at a country, regional and global level. Using anal cancer incidence estimates from 185 countries available through GLOBOCAN 2020, and region/country-specific proportions of SCCA vs non-SCCA from the Cancer Incidence in Five Continents (CI5) Volume XI database, we estimated country- and sex-specific SCCA incidence. Proportions of SCCA diagnosed in PLWHIV, and attributable to HIV, were calculated using estimates of HIV prevalence (UNAIDS 2019) and relative risk applied to SCCA incidence. Of 30 416 SCCA estimated globally in 2020, two-thirds occurred in women (19 792) and one-third among men (10 624). Fifty-three percent of male SCCA and 65% of female SCCA occurred in countries with a very high Human Development Index (HDI). Twenty-one percent of the global male SCCA burden occurred in PLWHIV (n = 2203), largely concentrated in North America, Europe and Africa. While, only 3% of global female SCCA burden (n = 561) occurred in PLWHIV, mainly in Africa. The global age-standardized incidence rate of HIV-negative SCCA was higher in women (0.55 cases per 100 000) than men (0.28), whereas HIV-positive SCCA was higher in men (0.07) than women (0.02). HIV prevalence reached >40% in 22 countries for male SCCA and in 10 countries for female SCCA, mostly in Africa. Understanding global SCCA burden by HIV status can inform SCCA prevention programs (through HPV vaccination, screening and HIV control) and help raise awareness to combat the disease., (© 2022 UICC.)

The objective of our study was to describe oral and genital human papillomavirus (HPV) infection prevalence and concordance by sexual orientation among US men using a nationally representative sample. We conducted a retrospective cross-sectional analysis of the 2013-2016 National Health and Nutrition Examination Survey. The survey conducts a physical examination and collects oral rinse and genital swab specimens; demographic and health behaviors are self-reported. We used descriptive statistics and multivariate regression models to estimate HPV infection prevalence and the likelihood of HPV infection, respectively. All analyses were adjusted for National Health and Nutrition Examination Survey design and weights, and statistical significance was tested at a 2-sided P value of less than .05. Men who have sex with men had a statistically significantly higher prevalence of oral HPV (high-risk, 9-valent, 4-valent, and HPV 16 and 18), genital HPV (9-valent, 4-valent, and HPV 16 and 18), and concordant oral and genital HPV (high-risk and 9-valent) infections compared with heterosexual men. Improved HPV prevention among men is needed., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Persons living with HIV (PLWH) are at high risk of developing anal high-grade squamous intraepithelial lesions (HSIL). We aimed to develop a prediction model for anal HSIL based on individual characteristics of PLWH., Methods: Cross-sectional study of PLWH aged ≥21 years who attended the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center from 2016 to 2022. The primary outcome was biopsy-confirmed anal HSIL. For each sex, relations between potential predictors and HSIL were examined using univariate (ULRM) and multivariable (MLRM) logistic regression models. Risk modelling was performed with MLRM and validated with bootstrapping techniques. The area under the ROC Curves (AUC) was estimated with 95% CI., Findings: HSIL was detected among 45.11% of patients, 68.48% were males, and 59.42% were ≥45 aged. Multivariable analysis showed that, in women, the only significant predictor for HSIL was having a previous abnormal anal cytology (p = 0.01). In men, significant predictors for HSIL were having a previous abnormal anal cytology (p < 0.001) and a history of infection with any gonorrhoea (p = 0.002). Other suggestive predictors for HSIL among women were obesity and smoking. No association between smoking and HSIL among men was observed (p < 0.05). The AUC estimated among women (0.732, 95% CI: 0.651-0.811) was higher than in men (0.689, 95% CI: 0.629-0.748)., Interpretation: Our results support that the inclusion of individual characteristics into the prediction model will adequately predict the presence of HSIL in PLWH., Funding: This work was supported by the NCI (Grants #U54CA096297, #R25CA240120), the NIGMS (Grant #U54GM133807), and the NIMHD (Grant #U54MD007587)., Competing Interests: Declaration of interests MSS reports support from NCI grants and from the AACR (2021 Faculty Scholar Award Minority and Serving Institution) to attend a conference meeting. ES declare no competing interests. TVR declare support from an NCI grant. LP declare no competing interests. JRC reports support from an NCI grant. AAD declare no competing interests. MT declare no competing interests. APO reports support from NCI grants and contracts with Merck, outside the submitted work.

Objectives: Cervical cancer incidence is rising in Puerto Rico (PR). Screening for cervical cancer could prevent the occurrence of the disease or lead to its early detection, translating to survival benefits. In this study, we evaluated the association of cervical cancer screening status with tumor diagnosis and survival among Hispanic women living in PR., Methods: We analyzed data for 506 incident cases of primary cervical cancer diagnosed from the period 2011-2014, identified through the PR Central Cancer Registry. We ascertained screening status 3 years before cervical cancer diagnosis using data from the period 2008-2014 from the PR Central Cancer Registry-Health Insurance Linkage Database. Patients were followed until 2019. Our outcomes of interest were stage at diagnosis and survival., Results: Most women (78.86%) were covered by public insurance (Medicare and/or Medicaid), and 69.57% underwent screening 3 years before their diagnosis. The proportion of cases diagnosed with localized stage was significantly greater among the screened group compared with those unscreened (43.5% vs 33.1%, p < .0001). Multivariate analysis showed that women insured through Medicaid were less likely to have been screened when compared with women with private insurance (odds ratio = 0.29; 95% CI = 0.16-0.52). Five-year survival was significantly greater among screened (72%) than unscreened (54%) women (p log-rank < 0.05). The multivariate Cox proportional hazards model showed that women who received screening had a 39% (hazard ratio [HR] = 0.61; 95% CI = 0.43-0.87) lower risk of death compared with unscreened women., Conclusion: Our findings exemplify survival benefits among women who underwent cervical cancer screening in PR. Interventions to improve screening uptake and adherence are a public health priority., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening., (© 2022 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Despite the overall national decline in Kaposi sarcoma (KS) incidence in the United States among persons living with HIV, previous studies suggest there might be specific subgroups of the US population that are associated with higher KS incidence rates than others. Using the 2001-2018 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program database, we assessed KS incidence trends among young men aged 20-34 years by race and ethnicity and geographic region. Statistical significance is 2-sided. The KS incidence rate increased nationally by 1.5% per year in non-Hispanic Black men, whereas the rate decreased statistically significantly by 3.5% per year in non-Hispanic White men. A statistically significant 3.3% per year increase among young non-Hispanic Black men in the South and no change among those living in non-South regions were observed. Targeted HIV prevention and treatment in young non-Hispanic Black men in the South and further research addressing the increased KS incidence and burden in this vulnerable population are needed., (© The Author(s) 2022. Published by Oxford University Press.)

The Centers for Disease Control and Prevention (CDC) promotes taking a 'bundling approach' (i.e., administering Tetanus, diphtheria toxoids, and acellular pertussis [Tdap] and human papillomavirus [HPV] vaccines in the same way and on the same day) for adolescent vaccinations. Recent trends and patterns in Tdap-HPV vaccination bundling in the USA remain undocumented. In addition, the implications of bundling Tdap-HPV vaccination for HPV vaccine series completion remain unknown. To address these critical knowledge gaps, we performed a retrospective study using a nationwide sample of privately insured adolescents (Optum's de-identified Clinformatics® Data Mart Database). Tdap-HPV vaccination bundling (per 100 Tdap vaccination encounters) during 2014-2018 was estimated overall, for 50 states, and by adolescents' age, sex, and provider specialties. Survival model estimated the likelihood of series completion among 9-14-year-old adolescents. From 2014 to 2018, 560,806 adolescents received a Tdap vaccine of which 172,604 (30.8%) received the HPV vaccines on the same day. Tdap-HPV vaccination bundling (per 100 Tdap vaccinations) increased nationally, from 22.9 in 2014 to 39.1 in 2018 (P trend  < 0.001); bundling was lowest in New York and New Jersey. The likelihood of receiving the Tdap and HPV vaccines bundled was higher for young and female adolescents. Adolescents who received their first HPV vaccine bundled with the Tdap vaccine were more likely to complete the series compared to those who received it alone (Hazards Ratio = 1.45; 1.43-1.48). HPV vaccination bundling has increased in recent years in the USA. The increased likelihood of HPV vaccine series completion provides important evidence supporting the adoption of same-day Tdap-HPV vaccine administration in clinical practice to boost HPV vaccination coverage., Competing Interests: Declaration of Competing Interest Dr. Giuliano received financial support from Merck, outside the submitted work, for her role as a member of several advisory boards and as a speaker at conference symposia. Drs. Ortiz and Deshmukh reported receiving consulting fee from Merck on unrelated projects. Dr. Sonawane has provided consultancy to Value Analytics Labs on unrelated projects. All other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Oropharyngeal cancer (OPC) incidence is rising rapidly among men in the United States of America (USA). We aimed to project the impact of maintaining the current HPV vaccination uptake and achieving 80% national (Healthy People) goal on OPC incidence and burden., Methods: We developed an open-cohort micro-simulation model of OPC natural history among contemporary and future birth cohorts of men, accounting for sexual behaviors, population growth, aging, and herd immunity. We used data from nationally representative databases, cancer registries from all 50 states, large clinical trials, and literature. We evaluated the status quo scenario (the current HPV vaccination uptake remained stable) and alternative scenarios of improvements in uptake rates in adolescents (aged 9-17 years) and young adults (aged 18-26 years) by 2025 to achieve and maintain the 80% goal. The primary outcome was to project OPC incidence and burden from 2009 to 2100. We also assessed the impact of disruption in HPV vaccine uptake during the COVID-19 pandemic., Findings: OPC incidence is projected to rise until the mid-2030s, reaching the age-standardized incidence rate of 9·8 (95% uncertainty interval [UI] 9·5-10·1) per 100 000 men, with the peak annual burden of 23 850 (UI, 23 200-24 500) cases. Under the status quo scenario, HPV vaccination could prevent 124 000 (UI, 117 000-131 000) by 2060, 400 000 (UI, 384 000-416 000) by 2080, and 792 000 (UI, 763 000-821 000) by 2100 OPC cases among men. Achievement and maintenance of 80% coverage among adolescent girls only, adolescent girls and boys, and adolescents plus young adults could prevent an additional number of 100 000 (UI, 95 000-105 000), 118 000 (UI, 113 000-123 000), and 142 000 (UI, 136 000-148 000) male OPC cases by 2100. Delayed recovery of the HPV vaccine uptake during the COVID-19 pandemic could lead to 600 (UI, 580-620) to 6200 (UI, 5940-6460) additional male OPC cases by 2100, conditional on the decline in the extent of the national HPV vaccination coverage and potential delay in rebounding., Interpretation: Oropharyngeal cancer burden is projected to rise among men in the USA. Nationwide efforts to achieve the HPV vaccination goal of 80% coverage should be a public health priority. Rapid recovery of the declined HPV vaccination uptake during the COVID-19 pandemic is also crucial to prevent future excess OPC burden., Funding: National Cancer Institute and National Institute on Minority Health and Health Disparities of the USA., Competing Interests: JC reported Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer and is a partner of Value Analytics Lab. ARG is a member of several Merck & Co, scientific and global advisory boards and her institution receives grants for research from Merck & Co, Inc. All other authors declare no competing interests., (© 2021 Published by Elsevier Ltd.)

Human papillomavirus (HPV)-associated cancer burden is rising in the United States. Trends in the incidence by county-level income and smoking prevalence remain undescribed. We used the Surveillance, Epidemiology, and End Results 21 database to ascertain HPV-associated cancers during 2000-2018. Trends were estimated by county-level income and smoking prevalence quartiles. Anal and vulvar cancer incidence among women and anal cancer incidence among men increased markedly in the lowest-income counties, whereas the increases were slower in the highest-income counties (eg, for vulvar cancer, incidence increased 1.9% per year, 95% confidence interval [CI] = 0.9% to 2.9%, in the lowest-income counties vs 0.8% per year, 95% CI = 0.6% to 1.1%, in the highest-income counties). In recent years, cervical cancer incidence plateaued (0.0% per year [95% CI = -0.5% to 0.5%]) in the highest-income counties; in the lowest-income counties, the annual percentage change was 1.6% per year (95% CI = -0.7% to 4.0%). Counties with high smoking prevalence had marked increases in incidence compared with their counterparts (eg, anal cancer among men increased 4.4% per year [95% CI = 2.7% to 6.0%] for those living in counties with the highest smoking prevalence vs 1.2% per year [95% CI = 0.7% to 1.7%] for those living in counties with the lowest smoking prevalence). Improved and targeted prevention is needed to combat the widening disparities., (© The Author(s) 2022. Published by Oxford University Press.)

Importance: Oropharyngeal cancer (OPC) incidence is rising among men in the US. Comprehensive assessments of nationwide trends in OPC incidence and mortality by demographics, tumor characteristics at diagnosis, and geography are lacking., Objective: We examined secular trends in OPC incidence and mortality rates in all 50 US states and the District of Columbia (DC)., Design, Setting, and Participants: In this cross-sectional study, we used the US Cancer Statistics data set to examine OPC incidence trends from 2001 through 2017. Observed and incidence-based mortality trends were evaluated using data from the National Center for Health Statistics and Surveillance Epidemiology and End Results program, respectively. Data analysis was conducted from January to April 2021., Results: Nationwide, 260 182 OPC cases were identified; 209 297 (80%) occurred in men, 168 674 (65%) with regional stage, and 142 068 (55%) in the Southeast and Midwest regions, during 2001 to 2017. Incidence of OPC increased nationally 2.7% per year among men, with a notable (over 3% per year) rise among non-Hispanic White men and in men aged 65 years and older. Overall, among women, the annual percentage change was 0.5% (95% CI, -0.28% to 1.22%). Among men, with a 3.1% per year rise (95% CI, 2.4% to 3.8%), regional-stage OPC incidence increased nearly 2-fold. Among women, regional-stage OPC incidence increased 1.0% per year (95% CI, 0.3% to 1.7%). Among men, OPC incidence increased in all states and regions except Alaska, DC, and Wyoming. Among men, the most pronounced increases (more than 3.5% per year) were clustered in the Southeast and Midwest regions. Among women, a rise of more than 2% per year was also concentrated in the Southeast and Midwest regions. Among men, OPC incidence-based mortality increased 2.1% per year (95% CI, 1.0% to 3.2%) overall in recent years (from 2006 to 2017). In contrast, among women, the annual percentage change in OPC incidence-based mortality was -1.2% (95% CI, -2.5% to 0.1%)., Conclusions and Relevance: The findings of this cross-sectional study suggest that the incidence of OPC has continued to increase nationally among men in the US, with rapid increases among the elderly population. The notable rise in regional-stage OPC and the concurrent recent rise in mortality among men is troubling and calls for urgent improvements in prevention. Distinct geographic patterns with notable rises in the Midwest and Southeast regions imply the need for improved and targeted prevention as well as future studies to understand etiological reasons for geographic disparities.

Introduction: Current smoking is a risk factor for anal cancer. Yet, its association with anal human papillomavirus infection (HPV) and anal high-grade squamous intraepithelial lesions (HSIL) remains unclear. We assessed the association of smoking with 1) anal high-risk HPV (HR-HPV) infection and 2) anal HSIL., Methods: Data from the baseline visit of patients from the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (May 2015- June 2021) was analyzed. Patients were eligible if they had information on smoking status, complete high-resolution anoscopy (HRA) with biopsy, and HR-HPV testing (n =  427). Logistic regression models estimated the odds ratio (OR) with 95% confidence intervals (CIs) adjusting for covariates., Results: Mean age was 44 ± 13 years, 69% were men, 74% were HIV-infected, and 25% reported being current smokers. 74% had anal HR-HPV infection. HSIL was diagnosed in 40% of patients. Current smokers had significantly higher odds (OR: 1.71, 95% CI: 1.04-2.82) of having HSIL compared to non-smokers after adjusting for age, sexual risk group, lifetime number of sexual partners, HIV status, and HR-HPV infection. Smoking was not associated with HR-HPV infection (OR: 1.56, 95% CI: 0.83-2.95) after adjusting for age, sexual risk group, lifetime number of sexual partners, and HIV status., Conclusions: Current smoking was associated with histologically confirmed HSIL but not with HR-HPV infection among this high-risk Hispanic population. Results highlight the need to explore targeted smoking cessation campaigns among populations at higher risk of developing HSIL, as an anal cancer prevention strategy., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The human papillomavirus (HPV) vaccine is effective at reducing the incidence of cervical cancer caused by HPV. Studies have shown that 1 dose of the HPV vaccine offers comparable protection against genital HPV infection as additional doses; however, it is unknown whether oral HPV prevalence also differs by number of vaccine doses. We examined differences in prevalence of oral HPV by number of doses using the National Health and Nutrition Examination Survey from 2009 to 2016. The prevalence of HPV 6, 11, 16, and 18 infections was statistically significantly lower in individuals who received 1 dose (0.3%, 95% confidence interval [CI] = 0.0% to 0.9%) or 2-3 doses (0.4%, 95% CI = 0.0% to 1.2%) compared with unvaccinated individuals (1.2%, 95% CI = 0.9% to 1.6%). Smokers, individuals who initiated oral sex at age 17 years or younger, and those with more than 2 oral sexual partners had higher rates of oral HPV infection. Ongoing prospective studies are essential to further evaluate the efficacy of a single-dose regimen for prevention of oral HPV., (© The Author(s) 2021. Published by Oxford University Press.)

Flexible large bandgap dielectric materials exhibiting ultra-fast charging-discharging rates are key components for electrification under extremely high electric fields. A polyoxafluoronorbornene ( m -POFNB) with fused five-membered rings separated by alkenes and flexible single bonds as the backbone, rather than conjugated aromatic structure typically for conventional high-temperature polymers, is designed to achieve simultaneously high thermal stability and large bandgap. In addition, an asymmetrically fluorinated aromatic pendant group extended from the fused bicyclic structure of the backbone imparts m -POFNB with enhanced dipolar relaxation and thus high dielectric constant without sacrificing the bandgap. m -POFNB thereby exhibits an unprecedentedly high discharged energy density of 7.44 J/cm 3 and high efficiency at 150 °C. This work points to a strategy to break the paradox of mutually exclusive constraints between bandgap, dielectric constant, and thermal stability in the design of all-organic polymer dielectrics for harsh condition electrifications., Competing Interests: The authors declare no competing interest.

Background: Anal cancer disproportionately affects people with HIV (PWH). High-grade squamous intraepithelial lesions (HSIL) are cancer precursors and treating them might prevent anal cancer. Data on adherence to HSIL treatment and surveillance is limited but needed to identify deficiencies of screening strategies., Methods: We collected data on high-resolution anoscopy (HRA) attendance and outcomes from 2009 to 2019 in a large urban anal cancer-screening program. Patients with an initial HSIL diagnosis were followed for return for HSIL electrocautery ablation within 6 months of index HSIL diagnosis, and follow-up HRA within 18 months of index HSIL diagnosis. We also evaluated predictors of these outcomes in univariable and multivariable analyses., Results: One thousand one hundred and seventy-nine unique patients with an anal HSIL diagnosis were identified and 684 (58%) returned for electrocautery ablation. Of those treated, only 174 (25%) and only 9% of untreated HSIL patients (47 of 495) underwent surveillance HRA within 18 months of index HSIL diagnosis. In multivariable analyses, black patients and PWH regardless of virologic control were less likely to undergo HSIL ablation within 6 months of HSIL diagnosis whereas patients with commercial insurance were more likely to be treated within 6 months of diagnosis. Among treated HSIL patients, PWH with viremia had a lower likelihood of engaging in post-treatment surveillance within 18 months of HSIL diagnosis., Discussion: Even in large specialized anal cancer screening programs adherence to HSIL treatment and surveillance is low. Psychosocial and economic determinants of health may impact retention in care. Addressing both personal and structural barriers to patient engagement may improve the effectiveness of anal cancer screening., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Gastroparesis is a potentially debilitating gastric motility disorder with limited treatment options. Highest efficacy treatments include gastric per-oral endoscopic myotomy (GPOEM) and surgical pyloromyotomy. This study compares the efficacy and safety of GPOEM versus laparoscopic pyloromyotomy for refractory gastroparesis., Methods: Patients who underwent GPOEM or laparoscopic pyloromyotomy for refractory gastroparesis from four centers across the USA and Latin America were included in a dedicated registry. Data collected included patient demographics, imaging, laboratory values, clinical success, gastroparesis cardinal symptom index, procedure time, pre-op and post-op gastric emptying times, adverse events, and hospital length of stay., Results: A total of 102 patients were included (mean age 47; 32.4% male): GPOEM n = 39, surgical pyloromyotomy n = 63.Technical success was 100% in both groups. Clinical success was 92.3% in the GPOEM group and 82.5% in the surgery group (P = 0.164). The GPOEM group had a significantly higher post-op GSCI score reduction by 1.3 units (P < 0.00001), post-op retention reduction at 2 h by 18% (P < 0.00001), post-op retention reduction at 4 h by 25% (P < 0.00001) and a lower procedure time by 20 min (P < 0.00001) as compared with surgery. GPOEM also had a lower hospital length of stay by 2.8 days (P < 0.00001). Adverse events were significantly fewer in the GPOEM group (13%) compared with surgery group (33.3%; P = 0.021). Mean blood loss in the GPOEM group was only 3.6 mL compared with 866 mL in the surgery group., Conclusions: The GPOEM may be a less invasive, safer, and more efficacious procedural treatment for refractory gastroparesis as compared with surgical pyloromyotomy., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Importance: Studies suggest the risk of suicide among people with cancer diagnosis is higher compared with the general population. However, little is known about how suicide risk among people diagnosed with cancer might vary according to area-level income and rurality., Objective: To examine whether the risks and patterns of suicide mortality among people with a cancer diagnosis differ by US county-level median income and rural or urban status., Design, Setting, and Participants: A retrospective, population-based cohort study following up individuals who were diagnosed with cancer between January 1, 2000, and December 31, 2016, was conducted. The Surveillance, Epidemiology, and End Results Program 18 registries (SEER 18) database was used to obtain data on persons diagnosed with a first primary malignant tumor. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were conducted from February 22 to October 14, 2020., Exposures: County-level median household income and urban or rural status., Main Outcomes and Measures: Standardized mortality ratios (SMRs) of suicide deaths and annual percentage changes (APCs) of SMRs., Results: The SEER 18 database included 5 362 782 persons with cancer diagnoses living in 635 counties. Most study participants were men (51.2%), White (72.2%), and older than 65 years (49.7%). Among them, 6357 persons died of suicide (SMR, 1.41; 95% CI, 1.38-1.44). People with cancer living in the lowest-income counties had a significantly higher risk (SMR, 1.94; 95% CI, 1.76-2.13) than those in the highest-income counties (SMR, 1.30; 95% CI, 1.26-1.34). Those living in rural counties also had significantly higher SMR than those in urban counties (SMR, 1.81; 95% CI, 1.70-1.92 vs SMR, 1.35; 95% CI, 1.32-1.39). For all county groups, the SMRs were the highest within the first year following cancer diagnosis. However, among people living in the lowest-income counties, the risk remained significantly high even after 10 or more years following cancer diagnosis (SMR, 1.83; 95% CI, 1.31-2.48). The comparative risk of suicide mortality within 1 year following cancer diagnosis significantly decreased over the years but then plateaued in the highest-income (2005-2015: APC, 2.03%; 95% CI, -0.97% to 5.13%), lowest-income (2010-2015: APC, 4.80%; 95% CI, -19.97% to 37.24%), and rural (2004-2015: APC, 1.83; 95% CI, -1.98% to 5.79%) counties., Conclusions and Relevance: This cohort study showed disparities in suicide risks and their patterns among people diagnosed with cancer by county-level income and rural or urban status. The findings suggest that additional research and effort to provide psychological services addressing these disparities among people with cancer may be beneficial.

In the present work, investigation of structural evolution of Cu 33 Zr 67 specimen during the cooling process from 2500 down to the 300 K, 200 K, 150 K, 100 K, 50 K, and 10 K has been performed at cooling rate of 5 K/ps using molecular dynamics simulation. The pair distribution function (PDF) reveals that Zr‒Zr pair causes the splitting of the first peak of the Cu 33 Zr 67 glass at a lower temperature with an increase in height. Splitting of the first and second peaks supports the presence of the inhomogeneous structure with a statistical average of crystal-like and disordered structural regions in the Cu 33 Zr 67 glass. Voronoi cluster analysis indicated that quasi icosahedral clusters such as < 284 > , < 0285 > , and < 0282 > ; mixed-type cluster such as < 0364 > ; and crystal-like clusters such as < 0446 > are responsible for stabilization of glassy phase at 300 K, 200 K, 150 K, 100 K, 50 K, and 10 K. Similarly, the maximum population of the Cu-centered and Zr-centered < 0286 > quasi icosahedral clusters support the stability of the glassy phase over the studied temperature range. Besides, the maximum population of Cu-centered < 0367 > and Zr-centered < 0364 > , < 0367 > , < 0363 > , and < 0365 > mixed-type clusters and Cu-centered < 0448 > and Zr-centered < 0448 > , < 0445 > , < 0446 > , and < 0444 > crystal-like clusters support the possibility of the presence of intermediate phase of CuZr 2 at lower temperatures as observed from PDFs. Mean square displacement (MSD) for the Cu 33 Zr 67 glass shows that the diffusion coefficient of Cu and Zr atoms reduces with decreasing temperature from 300 to 10 K. Diversity parameter (d) was found to decrease with decreasing temperature., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations., Methods: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive)., Results: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36)., Conclusions: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: In the US, safety concern has been identified as a primary barrier to initiating the human papillomavirus (HPV) vaccine. It is unclear if the public's sentiment concerning HPV vaccine safety aligns with postmarketing vaccine safety surveillance data., Objective: To perform a parallel assessment of trends in HPV vaccine safety concerns and HPV vaccine adverse event (AE) reporting., Design, Setting, and Participants: This study was a cross-sectional analysis of the National Immunization Survey (NIS) and Vaccine Adverse Event Reporting System (VAERS). Participants in the NIS were adolescents aged 13 to 17 years. AEs were reported to VAERS by patients, health care clinicians, or other sources. Statistical analysis was performed from October 2020 to May 2021., Main Outcomes and Measures: Secular trends in HPV vaccine safety concerns and spontaneous AE reporting for HPV vaccination from 2015 to 2018., Results: Caregivers of 39 364 unvaccinated adolescents with a mean (SD) age of 15.57 (0.08) years (26 996 White adolescents [62.9%], 22 707 male adolescents [56.1%], 11 392 privately insured [62.6%], and 32 674 above the poverty level [79.3%]) reported their reasons for not initiating the HPV vaccine series in the 2015-2018 NIS. Citing safety concerns as the primary reason for not initiating the HPV vaccine series increased from 13.0% (95% CI, 12.1%-14.0%) in 2015 to 23.4% (95% CI, 21.8%-25.0%) in 2018 (P for trend < .001), equating to a change from 170 046 to 259 157 US adolescents not initiating the vaccine because of safety concerns. The proportion of parents citing safety concerns as the main reason for HPV vaccine hesitancy increased in 30 states. The largest increases (more than 200%) were observed in California, Hawaii, South Dakota, and Mississippi. During 2015 to 2018, 16 621 AE reports following HPV vaccination were reported to VAERS. The AE reporting rate per 100 000 doses distributed decreased from 44.7 in 2015 to 29.4 in 2018 (P for trend < .001). The serious AE reporting rate, including those leading to hospitalizations, disability, life-threatening condition, or death did not change., Conclusions and Relevance: In this descriptive cross-sectional study, a rise in citing safety concerns was observed among parents with HPV vaccine hesitancy, contrary to the nonserious and serious AE reporting trends. These findings suggest an urgent need to combat the rising sentiment of safety concerns among caregivers to increase HPV vaccine confidence.

Background: Racial/ethnic minorities generally have a lower knowledge of human papillomavirus (HPV) and the HPV vaccine than non-Hispanic Whites. They are also less likely to have a regular healthcare provider (HCP). Given the role of HCPs in disseminating health information, we evaluated whether racial/ethnic disparities in HPV knowledge are moderated by regular HCP status., Methods: Data from the Health Information National Trends Survey Five (HINTS 5) Cycles One and Two (2017-2018) were analyzed. HPV and HPV vaccine knowledge were compared by regular HCP status across race/ethnicities. Independent partially-adjusted multivariable logistic regression models were used to assess the association between race/ethnicity and knowledge after controlling for sociodemographic characteristics. The resulting adjusted odds ratios were compared to those from fully-adjusted models that included HCP status., Results: After adjusting for regular HCP status, differences in knowledge persisted between racial/ethnic groups. Compared to Whites, Hispanics and Other race/ethnicities had significantly lower odds of having heard of HPV. Blacks, Hispanics, and Other race/ethnicities had significantly lower odds of having heard of the HPV vaccine., Conclusion: Racial/ethnic minorities had significantly lower levels of knowledge despite HCP status. These data suggest the need to address disparities in health information and strengthen provider-patient communication regarding HPV and the HPV vaccine.

Introduction: Squamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of anal precancers. Our objective is to determine compliance with annual anal canal self-sampling or clinician-sampling for human papillomavirus (HPV) DNA., Methods and Analysis: This is a prospective, randomised, two-arm clinical study to evaluate compliance with annual home-based versus clinic-based HPV DNA screening of anal canal exfoliated cells. The setting is primary care community-based clinics. Recruitment is ongoing for 400 HIV-positive and HIV-negative sexual minority men and transgender persons, aged > 25 years, English or Spanish speaking, no current use of anticoagulants other than nonsteroidal anti-inflammatory drugs and no prior diagnosis of anal cancer. Participants are randomised to either receive a swab in the mail for home-based collection of an anal canal specimen at 0 and 12 months (arm 1) or attend a clinic for clinician collection of an anal canal specimen at 0 and 12 months (arm 2). Persons will receive clinic-based Digital Anal Rectal Examinations and high-resolution anoscopy-directed biopsy to assess precancerous lesions, stratified by study arm. Anal exfoliated cells collected in the study are assessed for high-risk HPV persistence and host/viral methylation. The primary analysis will use the intention-to-treat principle to compare the proportion of those who comply with 0-month and 12-month sampling in the home-based and clinic-based arms. The a priori hypothesis is that a majority of persons will comply with annual screening with increased compliance among persons in the home-based arm versus clinic-based arm., Ethics and Dissemination: The study has been approved by the Medical College of Wisconsin Human Protections Committee. Results will be disseminated to communities where recruitment occurred and through peer-reviewed literature and conferences., Trial Registration Number: NCT03489707., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Proton beam therapy (PBT) is associated with less toxicity relative to conventional photon radiotherapy for head-and-neck cancer (HNC). Upfront delivery costs are greater, but PBT can provide superior long-term value by minimizing treatment-related complications. Cost-effectiveness models (CEMs) estimate the relative value of novel technologies (such as PBT) as compared with the established standard of care. However, the uncertainties of CEMs can limit interpretation and applicability. This review serves to (1) assess the methodology and quality of pertinent CEMs in the existing literature, (2) evaluate their suitability for guiding clinical and economic strategies, and (3) discuss areas for improvement among future analyses., Materials and Methods: PubMed was queried for CEMs specific to PBT for HNC. General characteristics, modeling information, and methodological approaches were extracted for each identified study. Reporting quality was assessed via the Consolidated Health Economic Evaluation Reporting Standards 24-item checklist, whereas methodologic quality was evaluated via the Philips checklist. The Cooper evidence hierarchy scale was employed to analyze parameter inputs referenced within each model., Results: At the time of study, only 4 formal CEMs specific to PBT for HNC had been published (2005, 2013, 2018, 2020). The parameter inputs among these various Markov cohort models generally referenced older literature, excluding many clinically relevant complications and applying numerous hypothetical assumptions for toxicity states, incorporating inputs from theoretical complication-probability models because of limited availability of direct clinical evidence. Case numbers among study cohorts were low, and the structural design of some models inadequately reflected the natural history of HNC. Furthermore, cost inputs were incomplete and referenced historic figures., Conclusion: Contemporary CEMs are needed to incorporate modern estimates for toxicity risks and costs associated with PBT delivery, to provide a more accurate estimate of value, and to improve their clinical applicability with respect to PBT for HNC., Competing Interests: Conflicts of Interest: Steven J. Frank, MD, is an Associate Editor of the International Journal of Particle Therapy. Outside of the submitted work, Dr Frank reports receiving personal fees as a consultant and advisory board member of Varian Medical Systems, Inc; grants and personal fees as director and founder of C4 Imaging, LLC; grants and honoraria as an advisor for Hitachi; honoraria from Boston Scientific; grants from Eli Lilly; grants from Elekta; honoraria from Augmenix; personal fees as a member of the board of directors of the National Comprehensive Cancer Center (NCCN); and other support as a scientific advisory board member for Breakthrough Chronic Care. Ashish A. Deshmukh PhD, MPH, reports receiving consulting fees from Merck on unrelated projects outside the submitted work. The authors have no additional conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Human papillomavirus (HPV)-associated anal and oropharyngeal cancer incidence has increased in recent years among US women. However, trends in incidence and burden (annual number of cases) of noncervical HPV-associated cancers relative to cervical cancer remain unclear. Using the 2001-2017 US cancer statistics dataset, we evaluated contemporary incidence trends and burden (annual number of cases) of HPV-associated cancers among women by anatomic site, race or ethnicity, and age. Overall, cervical cancer incidence plateaued among White women but continued to decline among Black and Hispanic women. Anal cancer incidence surpassed cervical cancer incidence among White women aged 65-74 years of age (8.6 and 8.2 per 100 000 in 2015) and 75 years or older (6.2 and 6.0 per 100 000 in 2014). The noncervical cancer burden (n  =  11 871) surpassed the cervical cancer burden (n  =  11 527) in 2013. Development of efficacious screening strategies for noncervical cancers and continued improvement in cervical cancer prevention are needed to combat HPV-associated cancers among women., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Human papillomavirus (HPV) and HPV vaccine knowledge and awareness are known to be lower among Hispanics compared to non-Hispanic whites. However, Hispanics in the US are a non-homogenous population, with significant differences by nativity, particularly between the US-and foreign-born individuals. We examined HPV and HPV vaccine awareness among foreign-born Hispanics, US-born Hispanics, and US-born non-Hispanic whites., Methods: We analyzed data from the Health Information National Trends Survey (HINTS) 5, cycles 1 (2017) and 2 (2018), the most recent HINTS datasets including nativity information. We used descriptive statistics and multivariable regression to compare awareness of HPV and the HPV vaccine among ethnicity/nativity subgroups., Results: Over 50% of foreign-born Hispanics had not heard of HPV, compared to 32% of US-born Hispanics (P < 0.01) and 33% of non-Hispanic whites (p < 0.01). Lack of HPV vaccine awareness among foreign-born Hispanics was not significantly different from US-born Hispanics (52% vs. 44%, p = 0.12), but was significantly lower compared to non-Hispanic whites (52% vs. 32%, p < 0.01). In multivariable analyses, non-Hispanic whites had over twice the odds of having heard of HPV than foreign-born Hispanics (p < 0.05), while US-born Hispanics had 75% higher odds (p < 0.05). Regarding HPV awareness, non-Hispanic whites had 95% higher odds of having heard of the HPV vaccine than foreign-born Hispanics (p < 0.05), while differences between US and foreign-born Hispanics were not significant., Conclusion: There are significant nativity-related differences in HPV and HPV vaccine awareness and knowledge among US-born Hispanics. Over 50% of foreign-born Hispanic adults are unaware of HPV and the HPV vaccine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Deshmukh received consulting fees from Merck on unrelated projects; the other authors have indicated they have no potential conflicts of interest to disclose.

In the present work, extended X-ray absorption fine-structure (EXAFS) investigations of Co 69 Fe x Si 21-x B 10 (x = 3, 5, 7) glassy ribbons were performed at the Co K-edge. The magnitude of the first peak of the Fourier transforms of the EXAFS signals is found to increase monotonically with increasing Si concentrations indicating the formation of the localized ordered structure at the atomic scale. The Co-Si coordination number (CN) increases at the expense of the CN of Co/Fe. Smaller interatomic distances are observed in the glassy phase compared with that in the crystalline phase which promotes the stability of the glassy phase. Calculations of the thermodynamic parameter (P HSS ), cohesive energy (E C ) and the atomic radius difference (δ) parameter show that the alloy composition Co 69 Fe 3 Si 18 B 10 has a good glass-forming ability (GFA) with the highest CN of Si compared with other compositions. A linear correlation of CN with that of the GFA parameter (P HSS ) exists and the CN also plays a crucial role in the GFA of the glassy alloys. This parameter should be considered in developing different GFA criteria.

Purpose: Squamous cell carcinoma of the anus (SCCA) is common among persons living with HIV (PLWH). We described SCCA incidence and survival among the general population and among PLWH in Puerto Rico (PR), along with mortality of anal cancer., Methods: PR HIV/AIDS Surveillance Program and the PR Central Cancer Registry databases were linked (2000-2016). Incidence rates (IRs) and trends (annual percent change [APC]) in SCCA and mortality rates and trends for anal cancer were estimated. Relative survival and relative excess risk (RER) of death were calculated., Results: From 2000 to 2016, 991 individuals in PR were diagnosed with anal cancer; 73% of cases were SCCA 9.1% of SCCA and 1.5% of non-SCCA cases were in PLWH ( P < .0001). SCCA incidence was higher among PLWH than the general population (IR = 27.7/100,000). Among PLWH, SCCA incidence (per 100,000) was the highest among men who have sex with men (IR = 60.5). From 2001-2016, SCCA incidence increased among the general population (APC: 4.90, P < .05); however, no significant change was observed among PLWH (APC = 0.19 and P = .96). The APC for anal cancer mortality in the general population was positive (3.9%) from 2000 to 2016, but not significant ( P > .05). The 5-year relative survival of SCCA was 56.9% among PLWH and 66.8% among the general population. In multivariate analysis, the RER of death for SCCA 5 years postdiagnosis was affected by stage at diagnosis (distant: RER = 7.6, 95% CI, 2.36 to 24.25) but not by PLWH status (RER = 1.4, 95% CI, 0.67 to 3.01)., Conclusion: Our findings highlight the relevance of anal cancer screening in PLWH and HPV vaccination in both PLWH and the general population in PR, which could have an impact on the disease trend in the next few decades.

Objective: The purpose of this study was to assess knowledge of human papillomavirus (HPV) as a cause of anal cancer among at-risk gay, bisexual, and other men who have sex with men (GBM)., Materials and Methods: Secondary analysis was conducted of cross-sectional data from 3 cycles of the Health Information National Trends Survey (2017, 2018, 2019). Results were reported for the subset of adults who identified as GBM (N = 212). Knowledge that HPV can cause anal cancer was the main outcome. Differences in knowledge were evaluated (using χ2 and multiple logistic regression) by demographic, health information factors, and access to care., Results: Sixty-eight percent of GBM were aware of HPV. Knowledge that HPV causes anal cancer was low (<20%) in the overall sample and sample of GBM (17.9%; 95% CI = 11.0-24.7). Gay, bisexual, and other men who have sex with men were no more knowledgeable that HPV causes anal cancer than heterosexual men (14.8%; 95% CI = 12.9-16.9; p = .376). College-educated GBM had higher odds (adjusted odds ratio = 3.50; 95% CI = 1.02-11.97) of knowing HPV causes anal cancer than GBM with no college degree. No other factors were associated with knowledge., Conclusions: Gay, bisexual, and other men who have sex with men are largely unaware that HPV can cause anal cancer, despite high awareness of HPV itself. This is concerning given that GBM are at increased risk of HPV-associated anal cancer than the general population. Our findings suggest that information about anal cancer and health information about the benefits of HPV vaccination for anal cancer prevention are only reaching a small subset of college-educated GBM. Targeted anal cancer education programs are needed., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020, ASCCP.)

Diabetes is a chronic metabolic disorder of the endocrine system characterized by an increase in blood glucose level. Several factors, such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction, play a vital role in the pathogenesis of diabetes, which further leads to serious diabetic complications. The diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors, such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. The process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol, and fructose. Therefore, diabetic wound requires more time to heal as compared to the normal wound. Healing time is delayed in diabetic wound due to many factors, such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wounds includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents are also one way to manage the diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV., Design: Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies., Methods: Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone., Results: 83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively., Conclusion: Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.

Background: Almost 20% of U.S. women remain at risk for cervical cancer due to their inability or unwillingness to participate in periodic clinic-based screening. Self-sampling has been shown to be an effective strategy for screening women for high-risk human papillomavirus (HR-HPV) infection in specific contexts. However, its effectiveness among medically underserved women in safety net health systems has not been evaluated. Furthermore, it is also unclear whether implementation strategies such as patient navigation can be used to improve the success of self-sample screening programs by addressing patient-level barriers to participation., Methods/design: The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) trial is a hybrid type 2 effectiveness-implementation pragmatic randomized controlled trial of mailed self-sample HPV testing. The aim is to assess the effectiveness of mailed self-sample HPV testing kits to improve cervical cancer screening participation among patients in a safety net health system who are overdue for clinic-based screening, while simultaneously assessing patient navigation as an implementation strategy. Its setting is a large, urban safety net health system that serves a predominantly racial/ethnic minority patient population. The trial targets recruitment of 2268 participants randomized to telephone recall (enhanced usual care, n = 756), telephone recall with mailed self-sample HPV testing kit (intervention, n = 756), or telephone recall with mailed self-sample HPV testing kit and patient navigation (intervention + implementation strategy, n = 756). The primary effectiveness outcome is completion of primary screening, defined as completion and return of mailed self-sample kit or completion of a clinic-based Pap test. Secondary effectiveness outcomes are predictors of screening and attendance for clinical follow-up among women with a positive screening test. Implementation outcomes are reach, acceptability, fidelity, adaptations, and cost-effectiveness., Discussion: Hybrid designs are needed to evaluate the clinical effectiveness of self-sample HPV testing in specific populations and settings, while incorporating and evaluating methods to optimize its real-world implementation. The current manuscript describes the rationale and design of a hybrid type 2 trial of self-sample HPV testing in a safety net health system. Trial findings are expected to provide meaningful data to inform screening strategies to ultimately realize the global goal of eliminating cervical cancer., Trial Registration: ClinicalTrials.gov NCT03898167 . Registered on 01 April 2019., Trial Status: Study start data: February 13, 2020. Recruitment status: Enrolling by invitation. Estimated primary completion date: February 15, 2023. Estimated study completion date: May 31, 2024. Protocol version 1.6 (February 25, 2020).

Background: Human papillomavirus (HPV) vaccine uptake among US adolescents is primarily dependent on the intent of their parents. To the best of our knowledge, an analysis quantifying parental intent to initiate and complete the HPV vaccine series in the USA at both the national and state level has not been done. We aim to estimate parental intent to initiate and complete the HPV vaccine series at the national-level and state-level and to identify reasons for lack of intent to initiate and complete the vaccine series., Methods: This cross-sectional study uses data from the adolescent component of the 2017-18 National Immunization Survey (NIS-Teen). Study participants were parents or caregivers of US adolescents aged 13-17 years, who were most knowledgeable about the immunisation status of the adolescents. The primary outcome was parental intent to vaccinate the adolescent in the next 12 months. The secondary outcomes were (1) the prevalence of reasons given for lack of intent to initiate and complete the HPV vaccine series, and (2) the relationship between receiving a recommendation from a health-care provider to vaccinate and intent to initiate the vaccination series. We computed national-level and state-level estimates for parental lack of intent to initiate and to complete the vaccine series; population-level estimates were derived using survey weights. A survey design-adjusted Wald F test was used for bivariate analysis. A multivariate logistic regression model was used to examine the association between health-care provider recommendation and parental intent to initiate the series. Analyses were stratified by history of health-care provider recommendation to initiate the HPV vaccine series., Findings: In 2017-18, the parent or caregiver of 82 297 US adolescents aged 13-17 years completed the NIS-Teen survey. 30 558 (37·1%) were unvaccinated and 9073 (10·8%) received only one HPV vaccine dose. Parents of 58·0% (17 171/29 086) of unvaccinated adolescents with data available on parental intent had no intention to initiate the HPV vaccine series. More than 65% of parents of unvaccinated adolescents in Idaho, Kansas, Michigan, Montana, Nebraska, North Dakota, Oklahoma, and Utah had no intention to initiate the HPV vaccine series. Parents of 23·5% (2166/9072) of initiators with data available on parental intent had no intention to complete the HPV vaccine series. More than 30% of parents in Arkansas, Florida, Georgia, Hawaii, Idaho, Utah, and West Virginia did not intend to complete the HPV vaccine series, whereas in the District of Columbia (11·2% [22/166]) and Rhode Island (20·4% [21/112]) parental lack of intent was relatively low (both regions have an HPV vaccine mandate). The most common reason for lack of intent among parents to initiate the vaccine for unvaccinated adolescents was safety concerns (22·8% [4182/16 455]); lack of a recommendation from a health-care provider (22·2% [440/1944]) was the most frequently cited reason for absence of intent to complete the series among parents of adolescents who received only one HPV vaccine dose. Receipt of a recommendation from a health-care provider was associated with greater odds of parental intent to initiate the HPV vaccine series (odds ratio 1·11, 95% CI 1·01-1·22). 45·5% (13 156/29 086) of parents of unvaccinated adolescents had reportedly received an HPV vaccine recommendation. Parents of 60·6% (7938/13 156) of unvaccinated adolescents with a recommendation from a health-care provider and data available on parental intent had no intention to initiate the series., Interpretation: Lack of parental intent to initiate and complete the HPV vaccine series for adolescents is a major public health concern in the USA. Combating vaccine safety concerns and strong recommendations from health-care providers could improve the currently suboptimal HPV vaccination coverage., Funding: US National Cancer Institute., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Squamous cell carcinoma of the anus (SCCA) incidence is rising in the United States. Study of incidence trends by stage at diagnosis, age-specific and birth cohort patterns, and trends in mortality could provide evidence for a true increase and etiological clues for the increase in incidence., Methods: Using the US Cancer Statistics dataset, we examined trends in SCCA incidence (2001-2015) and mortality (2001-2016) rates. Join-point regression was used to compute annual and average annual percentage change (AAPC). Incidence patterns by 5-year age group and birth cohort were evaluated using incidence rate ratios (IRRs) and age-period-cohort modeling., Results: SCCA incidence increased 2.7% per year (95% confidence interval [CI] = 2.1% to 3.3%), with pronounced increases in age groups 50 years and older. Distant-stage SCCA incidence tripled (AAPC = 8.6%, 95% CI = 5.4% to 12.0%, among men and AAPC = 7.5%, 95% CI = 4.8% to 10.2%, among women) and regional-stage SCCA incidence nearly doubled (AAPC = 4.7% for men and women) in both sexes; the AAPC for localized stage was 1.3% (95% CI = 0.6% to 2.0%) in men and 2.3% (95% CI = 1.8% to 2.8%) in women. Compared with adults born circa 1946, recently born black men (born circa 1986) had a nearly fivefold higher risk (IRR = 4.7, 95% CI = 2.1 to 10.2) of SCCA, and the risk doubled among white men (IRR = 2.0, 95% CI = 1.7 to 2.2) and white women (IRR = 2.1, 95% CI = 1.9 to 2.3) born after circa 1960. Anal cancer mortality rates increased 3.1% per year (95% CI = 2.6% to 3.5%) with statistically significant increases in age groups 50 years and older. SCCA incidence-based mortality increased 1.9% annually (95% CI = 0.5% to 3.4%), with a notable (4.9%, 95% CI = 2.4% to 7.3%, per year) rise in adults ages 60-69 years., Conclusion: The increase in SCCA incidence, particularly advanced-stage disease, and a similar increase in mortality suggest a true increase in the occurrence of SCCA. Future research and improved prevention are urgently needed to mitigate the increasing disease burden., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this study, firstly favorable glass-forming composition for the binary Co-Ni alloy is identified as Co 50 Ni 50 based on statistically evaluated thermodynamic parameters such as mixing enthalpy (∆H mix ), mixing entropy (∆S mix ), and topological parameter such as atomic size difference (δ). Secondly, molecular dynamics (MD) simulations have been performed to investigate the glass-forming ability (GFA) and cluster evolution during the rapid solidification (7.67 K/ps) of Co 50 Ni 50 under hydrostatic pressure (0, 0.25, 0.50, 1, 1.25, 2, 3, 5 GPa). It has been observed that with increasing pressure, glass transition temperature (T g ) also increases thereby increasing the GFA of Co 50 Ni 50 . Moreover, Voronoi cluster analysis reveals that quasi-icosahedral type clusters such as <0281> and <0282>, mixed types of cluster such as <0363>, <0364>, <1254>, and <0372> and crystal type clusters such as <0443> and <0444> have maximum population among the other clusters at different pressures at Co as well as Ni-centered atoms.