Characterization of Cervical Cancer Screening History Among Patients with Invasive Cervical Cancer: A Population-Based Approach.

•A high proportion of patients with cervical cancer were not up to date on screening at diagnosis.•Histology, age and path to diagnosis were associated with cervical cancer screening history.•Targeted health maintenance and screening guideline adherence are called for.

Sociodemographic and Occupational Characteristics Associated with Early and Continued COVID-19 Vaccine Uptake Among Healthcare Personnel: Monroe County, NY.

OBJECTIVE: Identify characteristics of healthcare personnel (HCP) who did not have timely initiation of the COVID-19 primary series, as well as HCP who did not receive a booster vaccine. METHODS: Characteristics of HCP enrolled in a COVID-19 vaccine effectiveness study between 12/28/2020-12/01/2022 were compared by timing of receipt of 1st mRNA dose, and by receipt of a booster dose. Data for this retrospective cohort analysis came from HCP working at a large healthcare system in Monroe County, New York, and included standardized questionnaires and verified vaccination status. HCP were categorized by whether they received their 1stmRNA COVID-19 vaccine between 12/14/2020-03/30/2021 (earlier) or 04/01/2021-09/28/2021 (later) based on timing of local vaccine eligibility and mandates, and by whether they received a 3rdmRNA booster dose by 12/01/22. Logistic regression models were run to identify characteristics of HCP who had later 1stdose receipt or did not receive a booster. RESULTS: 3,375 HCP were enrolled. Of these, 86.8 % had early initiation of their 1stCOVID-19 vaccine, and 85.0 % received a booster dose. Low education, low household income, younger age (<50), non-White race and public health insurance were all significant predictors of later receipt of 1stdose and lack of uptake of a booster. However, advanced professional role was only found to be a significant predictor of early 1stdose receipt. CONCLUSIONS: Continual monitoring of COVID-19 vaccine uptake among HCP to identify those less likely to receive new booster doses will be crucial to support targeted vaccine campaigns in this important population.

Influence of Community Determinants on Barriers and Facilitators to COVID-19 Vaccine Uptake: Regional Stakeholders' Perspectives.

Our study objective was to explore possible pathways by which neighborhood-level characteristics drive COVID-19 vaccination among communities experiencing health inequity and disparities. To do so, we conducted semi-structured qualitative interviews with stakeholders in the Finger Lakes region of New York between November 2022 through January 2023. Using a pre-developed interview guide informed by the Health Belief Model, we elicited county health commissioner, medical professional and community-health partner's perspectives regarding the impact community determinants have on shaping barriers to and facilitators of COVID-19 vaccine uptake, as well as recommended solutions for ensuring health equity in future vaccination efforts. Fifteen stakeholders were interviewed, of which 40% were county health commissioners, 27% hospital executives and 33% community-health organization partners. We identified diverse perceived and logistical barriers to COVID-19 vaccination that emerged as sub-themes including perceived risks outweighing the benefits of vaccination, concerns of vaccine safety, distrust stemming from changing scientific knowledge surrounding the vaccines, mistrust of the medical system, and challenges with transportation to and registering for vaccine appointments. Stakeholders reported these barriers were linked to the racial diversity, poverty, political conservatism, and availability of health care of the communities where they reported these were experienced. Notable solutions for improving equitable vaccination included facilitating structural access to vaccination and engaging community trusted messengers. Perceived and experienced barriers to COVID-19 vaccination may differ based upon the social, racial and economic composition of neighboring communities. Strategies for ensuring health equity in future vaccination campaigns should specifically target prevalent barriers based upon the community composition.

Immune mechanisms shape the clonal landscape during early progression of prostate cancer.

Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Using multicolor lineage tracing in genetically engineered mouse models and single-cell transcriptomics, we show that slowly progressing tumors contain a multiclonal landscape of relatively homogeneous subpopulations within a well-organized tumor microenvironment. In more advanced and aggressive tumors, however, the multiclonal landscape develops into competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that this dominant/minor landscape is associated with differential immunoediting, in which minor clones are marked by an increased expression of IFNγ-response genes and the T cell-activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNγ pathway can rescue minor clones from elimination. Notably, the immune-specific gene signature of minor clones exhibits a prognostic value for biochemical recurrence-free survival in human prostate cancer. These findings suggest new immunotherapy approaches for modulating clonal fitness and tumor progression in prostate cancer.

Bolstering the Measurement of Racial Inequity of COVID-19 Vaccine Uptake.

Inequities in COVID-19 vaccine uptake by racialized groups have been persistent throughout the vaccine rollout, leading to disparate burdens of COVID-19 outcomes. A cross-sectional study was conducted to determine COVID-19 vaccine uptake across racialized groups within the nine-county Finger Lakes region of New York State in December 2021. Cross-matching and validation were performed across multiple health information systems for the region to reduce the percentage of vaccine records with missing race information. Additionally, imputation techniques were applied to address the remaining missing values. Uptake of ≥1 dose of the COVID-19 vaccine by race was then examined. By December 2021, 828,551 individuals in our study region had received ≥1 dose of the COVID-19 vaccine, with ~25% having missing race values. Cross-matching and validation within existing records reduced this to ~7%. Uptake of ≥1 dose of a COVID-19 vaccine was greatest among individuals identifying as White, followed by those identifying as Black. The application of imputation techniques reduced the percent of missing race values to <1%; however, this reduction did not significantly change the distribution of vaccine uptake across race groups. Utilization of relevant health information systems, accompanied by imputation techniques, stands to greatly reduce the burden of missing race data within vaccine registries, facilitating accurate targeted interventions to mitigate inequities in COVID-19 vaccination.

A luminal intermediate cell state maintains long-term prostate homeostasis and contributes to tumorigenesis.

Cellular heterogeneity poses tremendous challenges for developing cell-targeted therapies and biomarkers of clinically significant prostate cancer. The origins of this heterogeneity within normal adult and aging tissue remain unknown, leaving cellular states and transcriptional programs that allow expansions of malignant clones unidentified. To define cell states that contribute to early cancer development, we performed clonal analyses and single cell transcriptomics of normal prostate from genetically-engineered mouse models. We uncovered a luminal transcriptional state with a unique "basal-like" Wnt/p63 signaling ( luminal intermediate , LumI) which contributes to the maintenance of long-term prostate homeostasis. Moreover, LumI cells greatly expand during early stages of tumorigenesis in several mouse models of prostate cancer. Genetic ablation of p63 in vivo in luminal cells reduced the formation of aggressive clones in mouse prostate tumor models. Finally, the LumI cells and Wnt signaling appear to significantly increase in human aging prostate and prostate cancer samples, highlighting the importance of this hybrid cell state for human pathologies with potential translational impact.

Racial Differences of Psychosocial Characteristics, HIV Risk-Taking and HIV Prevention Uptake between Men Who Have Sex with Men Only and Men Who Have Sex with Men and Women: A Community-Based Study in Two US Cities.

Bisexual behavior preference plays an important role in shaping HIV risks among men who have sex with men (MSM), yet few studies have examined the racial differences in the patterns of sexual risk and HIV prevention uptake between men who have sex with men and women (MSMW) and men who have sex with men only (MSMO). We conducted a community-based study to identify and compare psychosocial characteristics, sexual risks, HIV testing frequency, and pre-exposure prophylaxis (PrEP) engagement between Black and White MSMW and MSMO in two US cities. Findings indicate that White MSMW were most likely to engage in HIV risk-taking behaviors (e.g., alcohol/drug use before sex, condomless/group sex), while Black MSMW were least likely to recently test for HIV or report awareness (aPR: 0.32, 95% CI: 0.17-0.61), willingness (aPR: 0.58, 95% CI: 0.30-0.98), and use (aPR: 0.59, 95% CI: 0.31-0.93) of PrEP. Findings from our study supplement salient information for designing culturally tailored HIV prevention interventions for specific MSM subgroups in the US.

Assessing the Determinants of Quality of Life and the Impact on HIV Prevention Measures among HIV-Negative and Status-Unknown Young Men Who Have Sex with Men: A Study in Two U.S. Metropolitan Areas.

Young men who have sex with men (YMSM) in the United States (U.S.) are disproportionally burdened by HIV and experience adverse social determinants of health. Minimal research has examined quality of life (QoL) and psychosocial/behavioral determinants among HIV-negative or status-unknown YMSM. We conducted a study with YMSM from two U.S. cities to assess their QoL scores, and whether specific QoL domains (e.g., physical, psychological, social, and environment) were associated with their demographics, psychosocial determinants, behavioral risk factors, and HIV prevention measures. Black YMSM, YMSM of low socioeconomic status (below high school education, income < $20,000, and lack of health insurance), and YMSM who did not disclose their sexual orientation had the lowest QoL scores across all domains. Substance use and unprotected anal intercourse were negatively associated with men's physical/psychosocial health. Housing/food instability and perceived stress were among the strongest predictors of lower QoL in all domains. Higher physical/psychological and environment QoL scores were associated with a higher likelihood of HIV testing and PrEP use. The identification of YMSM within these demographic, behavioral, and psychosocial sub-groups is important for targeted intervention to enhance their well-being and engagement with HIV prevention.

Pre-Exposure Prophylaxis Care Continuum, Barriers, and Facilitators among Black Men Who Have Sex with Men in the United States: A Systematic Review and Meta-Analysis.

Pre-exposure prophylaxis (PrEP) represents a viable HIV prevention tool for black men who have sex with men (BMSM). However, aggregated evidence regarding the presentations and determinants of the PrEP continuum (e.g., awareness, willingness, intention, uptake and adherence) remains absent to empirically inform future intervention efforts. We meta-analytically summarized the prevalence and qualitatively synthesized key barriers/facilitators of the stages of the PrEP continuum among a pooled sample of 42,870 BMSM aggregated from 56 published studies. Our random-effect models indicated a pooled prevalence of PrEP awareness (50.8%, 95% CI: 43.6-58.0%, willingness/intention (58.2%, 95% CI: 52.0-68.1%) and uptake (15.5%, 95% CI: 12.8-18.2%). Qualitative summary revealed that perception of HIV risk, intersectional/PrEP-related stigma and medical mistrust were among the most quoted factors that influence PrEP use. BMSM remain underrepresented in key stages of the PrEP continuum. Futures interventions are continuously needed to target multilevel barriers/facilitators to enhance the PrEP continuum among BMSM.

Missed Opportunities for HPV Vaccination Among Vaccine-Eligible Women with High Grade Cervical Lesions.

BACKGROUND: Incidence of high-grade cervical lesions (HGCL) has declined in the U.S following the introduction of the human papillomavirus (HPV) vaccine in 2006. However, many women continue to be diagnosed with HGCLs, including those eligible to receive the vaccine but did not. We determined self-reported barriers to and correlates of HPV vaccination in vaccine-eligible women diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, 3 and adenocarcinoma in situ (CIN2+). METHODS: Data from a statewide surveillance system in Connecticut for CIN 2+ during 2008-2015 were used for this analysis. Enhanced surveillance data were collected for women residing in New Haven County, including HPV vaccine history and demographic factors, through chart review and patient interviews. Women who reported being unvaccinated were asked why they did not receive the vaccine. We evaluated trends in reasons for not receiving the vaccine using a two-sided Cochran Armitage trend test. Log-binomial analysis was used to assess associations between sociodemographic characteristics and vaccination status. RESULTS: Between 2008 and 2015, 1625 vaccine-eligible women were diagnosed with CIN2+, with 882 of these women reporting never receiving the HPV vaccine. The proportion of unvaccinated vaccine-eligible women did not significantly change from 2008 to 2015 (p = 0.18, range 49.1% to 60.0%). The most commonly reported reason for being unvaccinated was age/too old, followed by previous HPV diagnosis and no provider recommendation. Women who had public or no insurance were significantly more likely than privately insured women to report being unvaccinated (p = <0.001, p = 0.0034). CONCLUSIONS: Commonly cited barriers to vaccination, such as age/too old and previous HPV diagnosis, are not contraindications for vaccination. Furthermore, frequent reporting of no provider recommendation underscores the important role providers play in the immunization of their patients. These results indicate the need for greater efforts by providers to dispel myths about HPV vaccine eligibility and to promote vaccination for all of their eligible patients.