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Summary: Background: Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30 mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. Methods: Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25–81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020–2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. Findings: Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32–54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3 mm in diameter. Sensitivity and specificity of the ASE/ACE was 59.6% (95% CI 53.5–65.7%) and 80.2% (95% CI 76.6–83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70–0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p = 0.02). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. Interpretation: Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30 mm. Funding: National Cancer Institute.

Summary: 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).

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 treatmentrelated 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.

Summary: 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.

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.

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

Hormesis is a dose response phenomenon of cells and organisms to various types of stressors. Mild stress stimulates prosurvival pathways and makes the cells adaptive to stressful conditions. It is a widely used fundamental dose-response phenomenon in many biomedical and toxicological sciences, radiation biology, health science etc. Mild heat stress is an easily applicable hormetic agent that exerts consistent results. In the present investigations mouse cerebrocortical prefrontal neurons from E17 mouse embryos were grown in the laboratory on poly-L-lysine coated glass cover slips. The cells from the mild heat stressed group were subjected to a hyperthermic stress of 38 °C for 30 min every alternate day (i.e. mild heat stress was repeated after 48 h) up to the sixth day. After completion of twenty four hours of the final i.e. third exposure of the mild heat stress, the neurons were fixed for the cytochemical studies of neurofibrillary tangles, senile plaques, lipofuscin granules and Nissl substance. There was highly significant decrease in the neuropathological alterations (viz. deposition of Neurofibrillary tangles, deposition of senile plaques, accumulation of Lipofuscin granules) in the neurons from the mild heat stressed group as compared to control. Moreover, the Nissl substance was significantly preserved in the mild heat stressed group as compared to control. The results indicate that the applied mild heat stress (38 °C for 30 min) exerts beneficial effects on the prefrontal cerebrocortical neurons by slowing down the neuropathological alterations, suggesting the hormetic effect of the mild heat stress. Keywords: Hormesis, Mild heat stress, Neurofibrillary tangles, Senile plaques, Lipofuscin granules, Nissl substance

Despite the significant increase in the risk of colorectal cancer (CRC), one-third of individuals with diabetes who met screening recommendations, reported not being up-to-date on CRC screening in the United States. We determined the means through which individuals with type 2 diabetes (T2DM) learned about diabetes care; we further examined their associations with CRC screening uptake. This was a retrospective study of US adults aged 50–75 years diagnosed with T2DM (sample n = 5595, representing 14,724,933 Americans). Data from the 2011–2014 Medical Expenditure Panel Survey were analyzed to compare CRC screening uptake in four learning groups for diabetes care: (1) did not learn, (2) learning from health providers only, (3) learning from other sources (including online sources and group class), and (4) learning from health providers and other sources together (combined learning group). Overall, 70.4% individuals with T2DM were up-to-date with CRC screening during 2011–2014. In multivariate logistic regression analysis, the combined learning group had 1.32 (95% confidence interval, 1.01–1.74) times higher odds of being up-to-date on CRC screening than those who did not learn about diabetes care. The odds of being up-to-date on CRC screening were not significant for other learning groups. Our findings suggest that combined ways of health information delivery for diabetes care is associated with increased odds of being up-to-date on CRC screening among individuals with T2DM. Multimodal health information delivery has the potential to result in unintended, positive consequences in preventive care services use.