Leveraging COVID-era innovation for cervical cancer screening: Clinician awareness and attitudes toward self-sampling and rapid testing for HPV detection.

Cervical cancer screening rates are declining in the US, with persistent disparities among vulnerable populations. Strategies to better reach under-screened communities are needed. The COVID pandemic sparked major shifts in healthcare delivery, including the accelerated development and adoption of rapid diagnostic testing, broadened access to remote care, and growing consumer demand for self-testing, which could be leveraged for cervical cancer. Rapid tests for the detection of Human Papillomavirus (HPV) have the potential to improve cervical cancer screening coverage, and if coupled with patient-collected cervicovaginal samples, create an opportunity for self-testing. The objectives of this study were: 1) to examine whether COVID influenced clinician perspectives of rapid testing as a screening modality; and 2) to assess clinician awareness, perceived benefits and limitations, and willingness to adopt point-of-care HPV testing, patient self-sampling, and rapid HPV self-testing with self-collected samples. The methodology adopted consisted of an online cross-sectional survey (n = 224) and in-depth interviews (n = 20) were conducted with clinicians who perform cervical cancer screening in Indiana, ranked in the top ten states for cervical cancer mortality and with marked disparities across socio-demographic groups. The main findings show that about half the clinicians reported that the COVID pandemic had influenced their views on rapid testing as a screening modality both positively (greater public acceptability of rapid testing and impact on patient care) and negatively (concerns regarding accuracy of rapid tests). The majority of clinicians (82%) were willing to adopt rapid HPV testing at the point-of-care, while only 48% were willing to adopt rapid HPV self-testing with self-collected samples. In-depth interviews revealed provider concerns around patients' ability to collect their own sample, report results correctly, and return to the clinic for follow-up and other preventive care. Addressing clinician concerns about self-sampling and rapid HPV testing, such as ensuring that rapid tests include sample adequacy controls, is necessary to mitigate barriers to adoption for cervical cancer screening.

Clinician practices, knowledge, and attitudes regarding primary human papillomavirus testing for cervical cancer screening: A mixed-methods study in Indiana.

Primary human papillomavirus (HPV) testing, in which a high-risk HPV test is administered without cytology, was first included in 2018 US cervical cancer screening guidelines. Subsequent guidelines endorsed primary HPV testing as the preferred method for cervical cancer screening following evidence of its clinical and economic benefits, although many sources still indicate it as an option along with cytology and HPV/Pap co-testing. Primary HPV testing could be key to improving the declining cervical cancer screening rates in the US; however its adoption has been slow as clinicians are hesitant to make the change. Indiana ranks in the top ten states for cervical cancer mortality, with marked race-ethnic disparities in cervical cancer screening and low HPV vaccination rates. To examine clinician practices, knowledge, and attitudes regarding primary HPV testing, in 2021 we conducted an online cross-sectional survey (n = 224) and in-depth interviews (n = 20) with Indiana clinicians practicing cervical cancer screening. Only 3 % reported using primary HPV testing for eligible patients, and only 50 % were willing to adopt it as the preferred cervical cancer screening method for the recommended patient group. In a multivariable logistic regression model, knowledge of the effectiveness (aOR 2.58 [1.41-4.72]) and perceived benefit (aOR 7.35 [3.65-14.81]) of primary HPV testing predicted willingness to adopt. In-depth interviews revealed knowledge gaps, uncertainty, and perceived limitations of this method as the reasons for limited uptake of primary HPV testing. Targeted messages about the benefits and effectiveness may enhance clinician knowledge, acceptance, and adoption.

Completion of Social Drivers of Health Screenings in Pediatric Practices Participating in a Quality Improvement Initiative.

OBJECTIVES: The Indiana Chapter of the American Academy of Pediatrics (INAAP) participated in a national quality improvement project led by the AAP called Addressing Social Health and Early Childhood Wellness, which sought to screen for and address social drivers of health (SDoH), socioemotional development, and perinatal depression in pediatric practices through practice and system improvement. This project aims to evaluate positive SDoH screenings and subsequent referrals from participating Indiana practices. METHODS: Ten pediatric practices in mid-central Indiana participated in this collaboration between July 2020 and July 2021 and submitted information about clinic resources, patient demographics, and process measures. Monthly chart reviews of well-child visits assessed completion of SDoH screenings, discussion of screening results with families, and referrals for positive screens. Composite measures of performance were developed from chart review. RESULTS: Measures showed significant improvements in SDoH screening and identified opportunities for improvement in the care continuum. SDoH screenings of eligible patients significantly increased from 21% to 62% on average ( p = 0.0002). Needed referrals fulfilled increased from 37% to 57% ( p = 0.003) on average. Interestingly, no significant improvement was seen in referring patients who screened positive (81% vs 89%, p = 0.0949). CONCLUSION: This project provided a framework for successful development and efficient integration of screening and referral processes into clinic workflow. Implementing Plan-Do-Study-Act cycles, monthly chart reviews, and collaborative meetings facilitated increased documentation of screening, counseling, and referral for positive SDoH screens in participating practices. Future analysis should measure health outcomes and social and community capital derived by health systems and patients from such interventions.

Obstetrician/gynecologists' HPV vaccination recommendations among women and girls 26 and younger.

Background: Obstetrician/gynecologists (OB/GYNs) are well poised to vaccinate girls and young women against HPV, however little is known about if and how they recommend the HPV vaccine. This study aims to understand factors associated with strong and frequent HPV vaccine recommendations among OB/GYNs for patients 26 years and younger. Methods: 224 practicing U.S. OB/GYNs were surveyed for how strongly and frequently they recommend the HPV vaccine to patients 26 and younger. Provider beliefs, knowledge, and preferences surrounding the vaccine, as well as clinic and patient-level variables were examined as covariates. We then examined the relationships using multivariable logistic regression analyses. Results: Of the 224 respondents, 205 were included in the analysis, with 57% (n = 116) reporting strongly and frequently recommending the HPV vaccination to eligible patients 26 and younger. The regression showed two provider beliefs and two clinic-level attributes to be strongly associated with strong and frequent recommendations. Being a strong and frequent recommender was positively associated with believing other gynecologists frequently recommend the vaccine (aOR 24.33 95%CI[2.56-231.14]) and believing that 50% or more of their patients are interested in receiving the vaccine (aOR 2.77 95%CI[1.25-6.13]). The clinic-level attributes were having the vaccine stocked (aOR 2.66 95%CI[1.02-6.93]) and suburban (aOR 3.31 95%CI[1.07-10.19]) or urban (aOR 3.54 95%CI[1.07-11.76]) location versus rural. Conclusions: These findings suggest that OB/GYN peer support and educating OB/GYN about patients' interest in HPV vaccination may improve HPV vaccination. This work can inform clinic-level interventions including stocking the vaccine and focusing improvement efforts on rural clinics.

Pancreatic Cancer-Related Mutational Burden Is Not Increased in a Patient Cohort With Clinically Severe Chronic Pancreatitis.

INTRODUCTION: Chronic pancreatitis is associated with an increased risk of developing pancreatic cancer, and patients with inherited forms of pancreatitis are at greatest risk. We investigated whether clinical severity of pancreatitis could also be an indicator of cancer risk independent of etiology by performing targeted DNA sequencing to assess the mutational burden in 55 cancer-associated genes. METHODS: Using picodroplet digital polymerase chain reaction and next-generation sequencing, we reported the genomic profiles of pancreases from severe clinical cases of chronic pancreatitis that necessitated palliative total pancreatectomy with islet autotransplantation. RESULTS: We assessed 57 tissue samples from 39 patients with genetic and idiopathic etiologies and found that despite the clinical severity of disease, there was no corresponding increase in mutational burden. The average allele frequency of somatic variants was 1.19% (range 1.00%-5.97%), and distinct regions from the same patient displayed genomic heterogeneity, suggesting that these variants are subclonal. Few oncogenic KRAS mutations were discovered (7% of all samples), although we detected evidence of frequent cancer-related variants in other genes such as TP53, CDKN2A, and SMAD4. Of note, tissue samples with oncogenic KRAS mutations and samples from patients with PRSS1 mutations harbored an increased total number of somatic variants, suggesting that these patients may have increased genomic instability and could be at an increased risk of developing pancreatic cancer. DISCUSSION: Overall, we showed that even in those patients with chronic pancreatitis severe enough to warrant total pancreatectomy with islet autotransplantation, pancreatic cancer-related mutational burden is not appreciably increased.

Squaramide-Based Self-Associating Amphiphiles for Anion Recognition.

The synthesis and characterisation of two novel self-assembled amphiphiles (SSAs) SQS-1 and SQS-2 are reported. Both compounds, based on the squaramide motif, were fully soluble in a range of solvents and were shown to undergo self-assembly through a range of physical techniques. Self-assembly was shown to favour the formation of crystalline domains on the nanoscale but also fibrillar film formation, as suggested by SEM analysis. Moreover, both SQS-1 and SQS-2 were capable of anion recognition in DMSO solution as demonstrated using 1 H NMR and UV/Vis absorption spectroscopy, but displayed lower binding affinities for various anions when compared against other squaramide based receptors. In more competitive solvent mixtures SQS-1 gave rise to a colourimetric response in the presence of HPO42- that was clearly visible to the naked eye. We anticipate that the observed response is due to the basic nature of the HPO42- anion when compared against other biologically relevant anions.

Extracellular Trap-Mimicking DNA-Histone Mesostructures Synergistically Activate Dendritic Cells.

Extracellular traps (ETs), such as neutrophil extracellular traps, are a physical mesh deployed by immune cells to entrap and constrain pathogens. ETs are immunogenic structures composed of DNA, histones, and an array of variable protein and peptide components. While much attention has been paid to the multifaceted function of these structures, mechanistic studies of ETs remain challenging due to their heterogeneity and complexity. Here, a novel DNA-histone mesostructure (DHM) formed by complexation of DNA and histones into a fibrous mesh is reported. DHMs mirror the DNA-histone structural frame of ETs and offer a facile platform for cell culture studies. It is shown that DHMs are potent activators of dendritic cells and identify both the methylation state of DHMs and physical interaction between dendritic cells and DHMs as key tuning switches for immune stimulation. Overall, the DHM platform provides a new opportunity to study the role of ETs in immune activation and pathophysiology.

Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer.

BACKGROUND: Physical activity is associated with a lower risk of disease recurrence among colon cancer patients. Circulating tumor cells (CTC) are prognostic of disease recurrence among stage I-III colon cancer patients. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in CTCs. METHODS: Participants included 23 stage I-III colon cancer patients randomized into one of three groups: usual-care control, 150 min∙wk-1 of aerobic exercise (low-dose), and 300 min∙wk-1 of aerobic exercise (high-dose) for six months. CTCs from venous blood were quantified in a blinded fashion using an established microfluidic antibody-mediated capture device. Poisson regression models estimated the logarithmic counts of CTCs. RESULTS: At baseline, 78% (18/23) of patients had ≥1 CTC. At baseline, older age (-0.12±0.06; P = 0.04), lymphovascular invasion (0.63±0.25; P = 0.012), moderate/poor histology (1.09±0.34; P = 0.001), body mass index (0.07±0.02; P = 0.001), visceral adipose tissue (0.08±0.04; P = 0.036), insulin (0.06±0.02; P = 0.011), sICAM-1 (0.04±0.02; P = 0.037), and sVCAM-1 (0.06±0.03; P = 0.045) were associated with CTCs. Over six months, significant decreases in CTCs were observed in the low-dose (-1.34±0.34; P<0.001) and high-dose (-1.18±0.40; P = 0.004) exercise groups, whereas no significant change was observed in the control group (-0.59±0.56; P = 0.292). Over six months, reductions in body mass index (-0.07±0.02; P = 0.007), insulin (-0.08±0.03; P = 0.014), and sICAM-1 (-0.07±0.03; P = 0.005) were associated with reductions in CTCs. The main limitations of this proof-of-concept study are the small sample size, heterogenous population, and per-protocol statistical analysis. CONCLUSION: Exercise may reduce CTCs among stage I-III colon cancer patients. Changes in host factors correlated with changes in CTCs. Exercise may have a direct effect on CTCs and indirect effects through alterations in host factors. This hypothesis-generating observation derived from a small pilot study warrants further investigation and replication.