Histopathological biomarkers for predicting the tumour accumulation of nanomedicines.

The clinical prospects of cancer nanomedicines depend on effective patient stratification. Here we report the identification of predictive biomarkers of the accumulation of nanomedicines in tumour tissue. By using supervised machine learning on data of the accumulation of nanomedicines in tumour models in mice, we identified the densities of blood vessels and of tumour-associated macrophages as key predictive features. On the basis of these two features, we derived a biomarker score correlating with the concentration of liposomal doxorubicin in tumours and validated it in three syngeneic tumour models in immunocompetent mice and in four cell-line-derived and six patient-derived tumour xenografts in mice. The score effectively discriminated tumours according to the accumulation of nanomedicines (high versus low), with an area under the receiver operating characteristic curve of 0.91. Histopathological assessment of 30 tumour specimens from patients and of 28 corresponding primary tumour biopsies confirmed the score's effectiveness in predicting the tumour accumulation of liposomal doxorubicin. Biomarkers of the tumour accumulation of nanomedicines may aid the stratification of patients in clinical trials of cancer nanomedicines.

Exploratory Analysis of Concordance Between Clinician-Collected and Self-Sampled Human Papillomavirus Tests in a Small Cohort of Average- and High-Risk Patients.

Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n = 35) and high-risk (n = 12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n = 2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

Rural/Urban differences in uptake of preventive healthcare services: Variability in observed relationships across measures of rurality.

Rural residents are generally less likely to receive preventive healthcare than are urban residents, but variable measurement of rurality introduces inconsistency to these findings. We assessed the relationships between perceived and objective measures of rurality and uptake of preventive healthcare. In our sample, rural participants generally had equal or higher uptake of healthcare (i.e. private health insurance, check-up in the past year, being up-to-date on colorectal and cervical cancer screening) than urban participants. Importantly, the perceived measure of rurality performed similarly to the objective measures, suggesting that participant report could be a valid way to assess rurality in health studies. Significance for Public Health The ability to access routine preventive healthcare is a key component of public health. Comparing uptake of cancer screening in rural versus urban areas is one way to assess equity of healthcare access. Generally, rural areas have a higher burden of cancer than urban areas. The built environment, socioeconomic status, and patient perceptions can impact an individual's access to routine cancer screening. Preventive healthcare is of great importance to public health as a whole because screening can facilitate earlier diagnosis and more successful treatment for many preventable cancers, which may ultimately increase the quality and quantity of life.

Capivasertib combines with docetaxel to enhance anti-tumour activity through inhibition of AKT-mediated survival mechanisms in prostate cancer.

BACKGROUND/OBJECTIVE: To explore the anti-tumour activity of combining AKT inhibition and docetaxel in PTEN protein null and WT prostate tumours. METHODS: Mechanisms associated with docetaxel capivasertib treatment activity in prostate cancer were examined using a panel of in vivo tumour models and cell lines. RESULTS: Combining docetaxel and capivasertib had increased activity in PTEN null and WT prostate tumour models in vivo. In vitro short-term docetaxel treatment caused cell cycle arrest in the majority of cells. However, a sub-population of docetaxel-persister cells did not undergo G2/M arrest but upregulated phosphorylation of PI3K/AKT pathway effectors GSK3ß, p70S6K, 4E-BP1, but to a lesser extent AKT. In vivo acute docetaxel treatment induced p70S6K and 4E-BP1 phosphorylation. Treating PTEN null and WT docetaxel-persister cells with capivasertib reduced PI3K/AKT pathway activation and cell cycle progression. In vitro and in vivo it reduced proliferation and increased apoptosis or DNA damage though effects were more marked in PTEN null cells. Docetaxel-persister cells were partly reliant on GSK3ß as a GSK3ß inhibitor AZD2858 reversed capivasertib-induced apoptosis and DNA damage. CONCLUSION: Capivasertib can enhance anti-tumour effects of docetaxel by targeting residual docetaxel-persister cells, independent of PTEN status, to induce apoptosis and DNA damage in part through GSK3ß.

Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation.

More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling.

Addressing Social Risks to Accelerate Health Equity in Cancer Prevention and Control.

Addressing social risks in cancer prevention and control presents a new opportunity for accelerating cancer health equity. As members of the American Society of Preventive Oncology (ASPO) Cancer Health Disparities Special Interest Group, we describe the current state of science on social risks in oncology research and practice. To reduce and eliminate the unjust burden of cancer, we also provide recommendations for multilevel research examining social risks as contributors to inequities and the development of social risks-focused interventions. Suggestions for research and practice are provided within levels of the socio-ecological model, including the interpersonal, organizational, community, and policy levels.

Patterns of Cancer-Related Healthcare Access across Pennsylvania: Analysis of Novel Census Tract-Level Indicators of Persistent Poverty.

BACKGROUND: Persistent poverty census tracts have had ≥20% of the population living below the federal poverty line for 30+ years. We assessed the relationship between persistent poverty and cancer-related healthcare access across census tracts in Pennsylvania. METHODS: We gathered publicly available census tract-level data on persistent poverty, rurality, and sociodemographic variables, as well as potential access to healthcare (i.e., prevalence of health insurance, last-year check-up), realized access to healthcare (i.e., prevalence of screening for cervical, breast, and colorectal cancers), and self-reported cancer diagnosis. We used multivariable spatial regression models to assess the relationships between persistent poverty and each healthcare access indicator. RESULTS: Among Pennsylvania's census tracts, 2,789 (89.8%) were classified as non-persistent poverty, and 316 (10.2%) were classified as persistent poverty (113 did not have valid data on persistent poverty). Persistent poverty tracts had lower prevalence of health insurance [estimate = -1.70, standard error (SE) = 0.10], screening for cervical cancer (estimate = -4.00, SE = 0.17) and colorectal cancer (estimate = -3.13, SE = 0.20), and cancer diagnosis (estimate = -0.34, SE = 0.05), compared with non-persistent poverty tracts (all P < 0.001). However, persistent poverty tracts had higher prevalence of last-year check-up (estimate = 0.22, SE = 0.08) and screening for breast cancer (estimate = 0.56, SE = 0.15; both P < 0.01). CONCLUSIONS: Relationships between persistent poverty and cancer-related healthcare access outcomes differed in direction and magnitude. Health promotion interventions should leverage data at fine-grained geographic units (e.g., census tracts) to motivate focus on communities or outcomes. IMPACT: Future studies should extend these analyses to other states and outcomes to inform public health research and interventions to reduce geographic disparities.

Examining the roles of travel distance, medical mistrust, and cancer fatalism in the uptake of clinical cancer prevention among women in rural and urban US communities: A secondary data analysis.

Introduction: Rural adults are less likely to receive cancer screening than urban adults, likely due to systematic differences in community- and individual-level factors. The purpose of this study was to analyze the relative contributions of rurality, travel time, medical mistrust, and cancer fatalism in explaining uptake of clinical cancer prevention services. Methods: We conducted a secondary data analysis of 2019-2020 survey data from women, ages 45-65, in rural and urban counties in central Pennsylvania, examining rurality, travel time to a primary care provider, medical mistrust, and cancer fatalism, as well as uptake of guideline-recommended colorectal cancer screening, cervical cancer screening, and preventive check-up. Final models used multivariable logistic regression to assess the relationships among study variables, controlling for participant demographics. Results: Among 474 participants, 48.9 % resided in rural counties. Most participants had received clinical cancer prevention services (colorectal cancer screening: 55.4 %; cervical cancer screening: 82.8 %; preventive check-up in the last year: 75.4 %). Uptake of services was less common among participants with higher medical mistrust (colorectal cancer screening: adjusted odds ratio [aOR] = 0.87, 95 % confidence interval [CI] = 0.76-1.00; cervical cancer screening: aOR = 0.79, 95 % CI = 0.63-1.00; last-year check-up: aOR = 0.74, 95 % CI = 0.63-0.88). Conclusions: Patient attitudes, particularly medical mistrust, may contribute to rural/urban disparities in clinical cancer prevention among women. Community- and individual-level interventions are needed to improve cancer outcomes in rural areas.

Self-sampling tools to increase cancer screening among underserved patients: a pilot randomized controlled trial.

BACKGROUND: Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients. METHODS: We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated counties in Pennsylvania. Participants in the standard-of-care arm (n = 24) received screening reminder letters. Participants in the self-sampling arm (n = 24) received self-sampling tools for fecal immunochemical tests and human papillomavirus testing. We assessed uptake of screening (10-week follow-up), self-sampling screening outcomes, and psychosocial variables. Analyses used Fisher exact tests to assess the effect of study arm on outcomes. RESULTS: Cancer screening was higher in the self-sampling arm than the standard-of-care arm (colorectal: 75% vs 13%, respectively, odds ratio = 31.32, 95% confidence interval = 5.20 to 289.33; cervical: 79% vs 8%, odds ratio = 72.03, 95% confidence interval = 9.15 to 1141.41). Among participants who returned the self-sampling tools, the prevalence of abnormal findings was 24% for colorectal and 18% for cervical cancer screening. Cancer screening knowledge was positively associated with uptake (P < .05). CONCLUSIONS: Self-sampling tools can increase colorectal and cervical cancer screening among unscreened, underserved patients. Increasing the use of self-sampling tools can improve primary care and cancer detection among underserved patients. CLINICAL TRIALS REGISTRATION NUMBER: STUDY00015480.

We are all in this together: Rurality, Social cohesion, and COVID-19 prevention behaviors.

BACKGROUND: Social cohesion refers to an individual's sense of belonging to their community and correlates with health outcomes. Rural communities tend to have higher social cohesion than urban communities. Social cohesion is relatively understudied as a factor impacting COVID-19 prevention behaviors. This study explores the associations between social cohesion, rurality, and COVID-19 prevention behaviors. METHODS: Participants completed a questionnaire assessing rurality; social cohesion (subscales of (1) attraction to neighborhood, (2) acts of neighboring, and (3) sense of community); COVID-19 behaviors; and demographics. Chi-square tests were used to characterize participant demographics and COVID-19 behaviors. Bivariate and multivariable logistic regression models were used to analyze the relationship between COVID-19 outcomes and rurality, social cohesion, and demographics. RESULTS: Most participants (n = 2,926) were non-Hispanic White (78.2%) and married (60.4%); 36.9% were rural. Rural participants were less likely than urban participants to practice social distancing (78.7% vs 90.6%, P<.001) or stay home when sick (87.7% vs 93.5%, P<.001). Social distancing was more common among participants with higher "attraction to neighborhood" scores (adjusted odds ratio [aOR] = 2.09; 95% confidence interval [CI] = 1.26-3.47) but was less common among participants with higher "acts of neighboring" scores (aOR = 0.59; 95% CI = 0.40-0.88). Staying home when sick was also more common among participants with higher scores on "attraction to neighborhood" (aOR = 2.12; 95% CI = 1.15-3.91), and less common among participants with higher scores on "acts of neighboring" (aOR = 0.53; 95% CI = 0.33-0.86). CONCLUSIONS: Efforts to maximize COVID-19 behavioral prevention, particularly among rural communities, should emphasize the importance of protecting the health of one's neighbors and how to support one's neighbors without face-to-face interactions.

Impact of the physical-chemical properties of poly(lactic acid)-poly(ethylene glycol) polymeric nanoparticles on biodistribution.

Nanoparticle (NP) formulations are inherently polydisperse making their structural characterization and justification of specifications complex. It is essential, however, to gain an understanding of the physico-chemical properties that drive performance in vivo. To elucidate these properties, drug-containing poly(lactic acid) (PLA)-poly(ethylene glycol) (PEG) block polymeric NP formulations (or PNPs) were sub-divided into discrete size fractions and analyzed using a combination of advanced techniques, namely cryogenic transmission electron microscopy, small-angle neutron and X-ray scattering, nuclear magnetic resonance, and hard-energy X-ray photoelectron spectroscopy. Together, these techniques revealed a uniquely detailed picture of PNP size, surface structure, internal molecular architecture and the preferred site(s) of incorporation of the hydrophobic drug, AZD5991, properties which cannot be accessed via conventional characterization methodologies. Within the PNP size distribution, it was shown that the smallest PNPs contained significantly less drug than their larger sized counterparts, reducing overall drug loading, while PNP molecular architecture was critical in understanding the nature of in vitro drug release. The effect of PNP size and structure on drug biodistribution was determined by administrating selected PNP size fractions to mice, with the smaller sized NP fractions increasing the total drug-plasma concentration area under the curve and reducing drug concentrations in liver and spleen, due to greater avoidance of the reticuloendothelial system. In contrast, administration of unfractionated PNPs, containing a large population of NPs with extremely low drug load, did not significantly impact the drug's pharmacokinetic behavior - a significant result for nanomedicine development where a uniform formulation is usually an important driver. We also demonstrate how, in this study, it is not practicable to validate the bioanalytical methodology for drug released in vivo due to the NP formulation properties, a process which is applicable for most small molecule-releasing nanomedicines. In conclusion, this work details a strategy for determining the effect of formulation variability on in vivo performance, thereby informing the translation of PNPs, and other NPs, from the laboratory to the clinic.

Hospital- and county-level characteristics explain geographic variability in prices of cancer-related procedures: Implications for policy and interventions.

BACKGROUND: Healthcare costs in the U.S. are high and variable, which can hinder access and impact health outcomes across communities. This study examined hospital- and county-level characteristics to identify factors that explain geographic variation in prices for four cancer-related procedures. METHODS: Data sources included Turquoise Health, which compiles publicly-available price data from U.S. hospitals. We examined list prices for four procedures: abdominal ultrasound, diagnostic colonoscopy, brain MRI, and pelvis CT scan, which we linked to characteristics of hospitals (e.g., number of beds) and counties (e.g., metropolitan status). We used multilevel linear regression models to assess multivariable relationships between prices and hospital- and county-level characteristics. Supplementary analyses repeated these models using procedures prices for commercial insurance plans. RESULTS: For each procedure, list prices varied across counties (intraclass correlation: abdominal ultrasound = 23.2%; colonoscopy = 17.1%; brain MRI = 37.2%; pelvis CT = 50.9%). List prices for each procedure were associated with hospital ownership (all p < 0.001) and percent of population without health insurance (all p < 0.05). For example, list prices for abdominal ultrasound were higher for proprietary versus Government-owned hospitals (ß = 539.10, 95% confidence interval [CI]: 256.12, 822.08, p < 0.001) and for hospitals in counties with more uninsured residents (ß = 23.44, 95% CI: 2.55, 44.33, p = 0.03). Commercial insurance prices were negatively associated with metropolitan status. CONCLUSIONS: Prices for cancer-related healthcare procedures varied substantially, with considerable heterogeneity associated with county location as well as county-level social determinants of health (e.g., health insurance coverage). Interventions and policy changes are needed to alleviate the financial burden of cancer care among patients, including geographic variation in prices for cancer-related procedures.

The Impact of the COVID-19 Pandemic on Cancer Mortality in Pennsylvania: A Retrospective Study with Geospatial Analysis.

BACKGROUND: We sought to quantify the impact of the COVID-19 pandemic on cancer mortality and identify associated factors in Pennsylvania. METHODS: The retrospective study analyzed cross-sectional cancer mortality data from CDC WONDER for 2015 through 2020 for Pennsylvania and its 67 counties. The spatial distributions of 2019, 2020, and percentage change in age-adjusted mortality rates by county were analyzed via choropleth maps and spatial autocorrelation. A Wilcoxon Signed Rank Test was used to analyze whether the rates differed between 2019 and 2020. Quasi-Poisson and geographically weighted regression at the county level were used to assess the association between the 2019 rates, sex (percent female), race (percent non-White), ethnicity (percent Hispanic/Latino), rural-urban continuum codes, and socioeconomic status with the 2020 rates. RESULTS: At the state level, the rate in 2020 did not reflect the declining annual trend (-2.7 per 100,000) in the rate since 2015. Twenty-six counties had an increase in the rate in 2020. Of the factors examined, the 2019 rates were positively associated with the 2020 rates, and the impact of sociodemographic and geographic factors on the 2020 rates varied by county. CONCLUSIONS: In Pennsylvania, the 2020 cancer mortality rates did not decline as much as reported before the COVID-19 pandemic. The top five cancer types by rate were the same type for 2019 and 2020. Future cancer control efforts may need to address the impact of the COVID-19 pandemic on trends and geospatial distribution in cancer mortality.

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance.

Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for estrogen receptor-positive (ER+) breast cancer, as they achieve greater inhibition of ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated the preclinical pharmacology and efficacy of the next-generation oral SERD camizestrant (AZD9833) and assessed ER-co-targeting strategies by combining camizestrant with CDK4/6 inhibitors (CDK4/6i) and PI3K/AKT/mTOR-targeted therapy in models of progression on CDK4/6i and/or ET. Camizestrant demonstrated robust and selective ER degradation, modulated ER-regulated gene expression, and induced complete ER antagonism and significant antiproliferation activity in ESR1 wild-type (ESR1wt) and mutant (ESR1m) breast cancer cell lines and patient-derived xenograft (PDX) models. Camizestrant also delivered strong antitumor activity in fulvestrant-resistant ESR1wt and ESR1m PDX models. Evaluation of camizestrant in combination with CDK4/6i (palbociclib or abemaciclib) in CDK4/6-naive and -resistant models, as well as in combination with PI3Kαi (alpelisib), mTORi (everolimus), or AKTi (capivasertib), indicated that camizestrant was active with CDK4/6i or PI3K/AKT/mTORi and that antitumor activity was further increased by the triple combination. The response was observed independently of PI3K pathway mutation status. Overall, camizestrant shows strong and broad antitumor activity in ER+ breast cancer as a monotherapy and when combined with CDK4/6i and PI3K/AKT/mTORi. SIGNIFICANCE: Camizestrant, a next-generation oral SERD, shows promise in preclinical models of ER+ breast cancer alone and in combination with CDK4/6 and PI3K/AKT/mTOR inhibitors to address endocrine resistance, a current barrier to treatment.

Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models.

Combining the selective AKT inhibitor, capivasertib, and SERD, fulvestrant improved PFS in a Phase III clinical trial (CAPItello-291), treating HR+ breast cancer patients following aromatase inhibitors, with or without CDK4/6 inhibitors. However, clinical data suggests CDK4/6 treatment may reduce response to subsequent monotherapy endocrine treatment. To support understanding of trials such as CAPItello-291 and gain insight into this emerging population of patients, we explored how CDK4/6 inhibitor treatment influences ER+ breast tumour cell function and response to fulvestrant and capivasertib after CDK4/6 inhibitor treatment. In RB+, RB- T47D and MCF7 palbociclib-resistant cells ER pathway ER and Greb-1 expression were reduced versus naïve cells. PI3K-AKT pathway activation was also modified in RB+ cells, with capivasertib less effective at reducing pS6 in RB+ cells compared to parental cells. Expression profiling of parental versus palbociclib-resistant cells confirmed capivasertib, fulvestrant and the combination differentially impacted gene expression modulation in resistant cells, with different responses seen in T47D and MCF7 cells. Fulvestrant inhibition of ER-dependent genes was reduced. In resistant cells, the combination was less effective at reducing cell cycle genes, but a consistent reduction in cell fraction in S-phase was observed in naïve and resistant cells. Despite modified signalling responses, both RB+ and RB- resistant cells responded to combination treatment despite some reduction in relative efficacy and was effective in vivo in palbociclib-resistant PDX models. Collectively these findings demonstrate that simultaneous inhibition of AKT and ER signalling can be effective in models representing palbociclib resistance despite changes in pathway dependency.

Increasing the adoption of evidence-based communication practices for HPV vaccination in primary care clinics: The HPV ECHO study protocol for a cluster randomized controlled trial.

BACKGROUND: The safe, highly-effective human papillomavirus (HPV) vaccine remains underused in the US. The Announcement Approach Training (AAT) has been shown to effectively increase HPV vaccine uptake by training providers to make strong vaccine recommendations and answer parents' common questions. Systems communications, like recall notices, can further improve HPV vaccination by reducing missed clinical opportunities for vaccination. Never tested in supporting HPV vaccination, the ECHO (Extension for Community Healthcare Outcomes) model is a proven implementation strategy to increase best practices among healthcare providers. This trial uses a hybrid effectiveness-implementation design (type II) to evaluate two ECHO-delivered interventions intended to increase HPV vaccination rates. METHODS: This 3-arm cluster randomized controlled trial will be conducted in 36 primary care clinics in Pennsylvania. Aim 1 evaluates the impact of HPV ECHO (AAT to providers) and HPV ECHO+ (AAT to providers plus recall notices to vaccine-declining parents) versus control on HPV vaccination (≥1 dose) among adolescents, ages 11-14, between baseline and 12-month follow-up (primary outcome). Using a convergent mixed-methods approach, Aim 2 evaluates the implementation of the HPV ECHO and HPV ECHO+ interventions. Aim 3 explores exposure to and impact of vaccine information from providers and other sources (e.g., social media) on secondary acceptance among 200 HPV vaccine-declining parents within 12 months. DISCUSSION: We expect to demonstrate the effectiveness and evaluate the implementation of two highly scalable interventions to increase HPV vaccination in primary care clinics. Our study seeks to address the communication needs of both providers and parents, increase HPV vaccination, and, eventually, prevent HPV-related cancers. TRIAL REGISTRATION: ClinicalTrials.govNCT04587167. Registered on October 14, 2020.

Behaviors and Advocacy Related to COVID-19 among Cancer Patients: The Health Belief Model and Opportunities for Messaging and Education.

Cancer patients have an increased risk of severe COVID-19 outcomes and were recommended to be vaccinated, wear a mask, practice social distancing, and increase hand hygiene. We used the Health Belief Model (HBM) to identify constructs that were associated with the likelihood of adhering to and advocating for CDC COVID-19 prevention recommendations. We surveyed adult cancer patients who had an onsite appointment at the Penn State Cancer Institute or at the Hematology and Oncology Associates of Northeastern Pennsylvania. Survey measures included adherence to and informing others of COVID-19 recommendations as well as HBM constructs. Relationships between HBM constructs and outcomes were assessed with Spearman's correlation and multivariable ordinal logistic regression. Of the 106 participants who completed the survey for our objectives of interest, 76% always wore a mask, 29% always practiced social distancing, and 24% washed their hands at least 10 times a day. Limited advocacy behaviors were captured for the COVID-19 vaccine (30%), social distancing (36%), and wearing masks (27%). Perceived benefits, perceived barriers, and cues-to-action were positively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients, whereas perceived susceptibility and self-efficacy were negatively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients. Perceived benefits may be the strongest predictor for adherence and advocacy for specific COVID-19 guidelines. Future messaging and educational campaigns focused on improving adherence to or advocacy of specific health behaviors should be informed by the HBM and originate from multiple outlets.

The role of social cohesion in explaining rural/urban differences in healthcare access and health status among older adults in the mid-Atlantic United States.

Social cohesion can influence health. It is higher among rural versus urban residents, but the burden of chronic disease is higher in rural communities. We examined the role of social cohesion in explaining rural/urban differences in healthcare access and health status. Rural (n = 1080) and urban (n = 1846) adults (ages 50+) from seven mid-Atlantic U.S. states completed an online, cross-sectional survey on social cohesion and health. We conducted bivariate and multivariable analyses to evaluate the relationships of rurality and social cohesion with healthcare access and health status. Rural participants had higher social cohesion scores than did urban participants (rural: mean = 61.7, standard error[SE] = 0.40; urban: mean = 60.6, SE = 0.35; adjusted beta = 1.45, SE = 0.54, p < .01). Higher social cohesion was associated with greater healthcare access: last-year check-up: adjusted odds ratio[aOR] = 1.25, 95% confidence interval[CI] = 1.17-1.33; having a personal provider: aOR = 1.11, 95% CI = 1.03-1.18; and being up-to-date with CRC screening: aOR = 1.17, 95% CI = 1.10-1.25. In addition, higher social cohesion was associated with improved health status: higher mental health scores (adjusted beta = 1.03, SE = 0.15, p < .001) and lower body mass index (BMI; beta = -0.26, SE = 0.10, p = .01). Compared to urban participants, rural participants were less likely to have a personal provider, had lower physical and mental health scores, and had higher BMI. Paradoxically, rural residents had higher social cohesion but generally poorer health outcomes than did urban residents, even though higher social cohesion is associated with better health. These findings have implications for research and policy to promote social cohesion and health, particularly for health promotion interventions to reduce disparities experienced by rural residents.