Cancer prevention research (Philadelphia, Pa.)最新文献

Vaginal dysbiosis is implicated in persistent human papillomavirus (HPV) infection and cervical cancer. Yet, there is a paucity of data on the vaginal microbiome in Native American communities. Here, we aimed to elucidate the relationships between microbiome, HPV, sociodemographic, and behavioral risk factors to better understand an increased cervical cancer risk in Native American women. In this pilot study, we recruited 31 participants (16 Native American and 15 non-Native women) in Northern Arizona and examined vaginal microbiota composition, HPV status, and immune mediators. We also assessed individuals' sociodemographic information and physical, mental, sexual, and reproductive health. Overall, microbiota profiles were dominated by common Lactobacillus species (associated with vaginal health) or a mixture of bacterial vaginosis-associated bacteria. Only 44% of Native women exhibited Lactobacillus dominance, compared with 58% of non-Native women. Women with vaginal dysbiosis also had elevated vaginal pH and were more frequently infected with high-risk HPV. Furthermore, we observed associations of multiple people in a household, lower level of education, and high parity with vaginal dysbiosis and abundance of specific bacterial species. Finally, women with dysbiotic microbiota presented with elevated vaginal levels of proinflammatory cytokines. Altogether, these findings indicate an interplay between HPV, vaginal microbiota, and host defense, which may play a role in the cervical cancer disparity among Native American women. Future longitudinal studies are needed to determine the mechanistic role of vaginal microbiota in HPV persistence in the context of social determinants of health toward the long-term goal of reducing health disparities between non-Hispanic White and Native American populations. Prevention Relevance: Cervical cancer disproportionally affects Native American women. Sociodemographic and behavioral factors might contribute to this disparity via alteration of vaginal microbiota. Here, we show the association between these factors and vaginal dysbiosis and immune activation, which can be implicated in high-risk HPV infection among Native American and other racial/ethnic populations.

In October 2023, Nigeria integrated the single-dose human papillomavirus (HPV) vaccine into its routine immunization program, aiming to protect 7.7 million girls aged 9 to 14 years. This milestone in the fight against HPV-related cancers, especially cervical cancer, faces significant challenges due to high vaccine rejection rates driven by misinformation and cultural barriers. Despite the vaccine's proven safety and efficacy, uptake remains low. This communication highlights the urgent need for a comprehensive public health education campaign to address these barriers. Proposed strategies include leveraging digital health technologies, integrating HPV education into school curricula, training community health workers, engaging religious and cultural leaders, and launching media campaigns featuring personal narratives. Implementing these evidence-based interventions is crucial for dispelling myths, misconceptions, and skepticism surrounding HPV vaccines. This will enhance acceptance and uptake, ultimately reducing cervical cancer mortality in Nigeria.

Currently, eight million people in the United States suffer from cancer and it is a major global health concern. Early detection and interventions are urgently needed for all cancers, including colorectal cancer. Colorectal cancer is the third most common type of cancer worldwide. Based on the diagnostic efforts to general awareness and lifestyle choices, it is understandable why colorectal cancer is so prevalent today. There is a notable lack of awareness concerning the impact of this cancer and its connection to lifestyle elements, as well as people sometimes mistaking symptoms for a different gastrointestinal condition. Artificial intelligence (AI) may assist in the early detection of all cancers, including colorectal cancer. The usage of AI has exponentially grown in healthcare through extensive research, and since clinical implementation, it has succeeded in improving patient lifestyles, modernizing diagnostic processes, and innovating current treatment strategies. Numerous challenges arise for patients with colorectal cancer and oncologists alike during treatment. For initial screening phases, conventional methods often result in misdiagnosis. Moreover, after detection, determining the course of which colorectal cancer can sometimes contribute to treatment delays. This article touches on recent advancements in AI and its clinical application while shedding light on why this disease is so common today.

This study examined the association among cancer history, social support, and up-to-date colorectal cancer (CRC) screening among four racial/ethnic groups. We conducted a cross-sectional analysis using data on respondents aged 45 to 75 years from the 2022 Behavioral Risk Factor Surveillance System. Our outcome of interest was CRC screening and exposures of interest were race/ethnicity, cancer history, and social support. Weighted multivariable logistic regression was performed. Among 73,869 adults, the CRC screening rate was 66.8% with the highest rate in non-Hispanic (NH), Whites (72.2%), and the lowest in Hispanics (52.6%). Screening rates were higher in adults with a cancer history (81.9%) and those having social support (69%). Hispanic adults with a cancer history had lower screening use (50.9% vs. 77.4% in the no cancer history group; P value < 0.001). Regardless of race/ethnicity, adults without social support had lower screening utilization (P value < 0.05). In effect modification, NH White adults who reported no cancer history and lack of social support were 12% less likely to have CRC screening than those with social support but without cancer history (OR, 0.88; 95% confidence intervals, 0.79-0.98). Similar results were observed among Hispanic adults without a cancer history and social support, with 37% less likely to have CRC screening than those with social support but no cancer history (OR, 0.63; 95% confidence intervals, 0.42-0.93). NH White and Hispanic adults without a cancer history and limited social support were less likely to have CRC screening uptake. By implementing culturally tailored interventions that address social support needs, greater CRC screening compliance may be increased among these populations. Prevention Relevance: Adherence to CRC screening recommendations reduces cancer incidence and mortality. Effective implementation of culturally tailored interventions that address social support needs and consider cancer history have the potential for improving CRC screening compliance among NH White and Hispanic adults without a cancer history.

Head and neck squamous cell carcinoma (HNSCC) is a spectrum of heterogeneous malignancies. A variety of genetic, environmental, and lifestyle factors contribute to the development of HNSCC. Carcinogenesis is a multistep process in which cell proliferation-associated oncogenes and cell-cycle regulation-associated tumor suppressor genes are dysregulated, resulting in premalignant lesions. Immune evasion is a critical step in the progression of benign lesions to advanced cancer. This review discusses the advances that have been made in chemoprevention strategies for HNSCC. The rationale for the use of chemopreventive agents to inhibit head and neck cancer development is highlighted by the positive outcomes of several clinical trials. We discuss the potential of some of the commonly studied agents including vitamin A analogs, EGFR inhibitors, COX-2 inhibitors, metabolic modulators, and natural compounds such as green tea, as well as immunotherapy and photodynamic therapy to prevent HNSCC. Our review provides insight into the potential benefits of these agents and the gaps that remain to be addressed. The published results reaffirm the promise of chemoprevention in head and neck cancer and suggest that continued exploration is needed to overcome the limitations. Because the current focus on chemopreventive agents is limited, major efforts in precision oncology approaches and substantial increase in funding will promote research into chemoprevention, which will eventually decrease the incidence of HNSCC.

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery 3 days/week at 10 mg/kg, beginning when the mice were 2 months old and lasting 3 months. We euthanized the mice at 5 months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single-cell RNA sequencing (scRNA-seq) of pancreata of AB-680-treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment. Prevention Relevance: Previous studies found PanIN lesions in healthy pancreata. Not all progress to PDAC, suggesting a window for enhanced antitumor immunity through immunoprevention therapy. CD73 inhibition in our study prevents PanIN progression, reduces immune-suppressive macrophages and expands TCR and BCR unique clonotypes, highlighting an encouraging therapeutic avenue for high-risk individuals.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.

In this secondary analysis of specimens from the CANTOS trial, the investigators find that patients with clonal hematopoiesis mutations, particularly in the TET2 gene, predict a benefit of decreased cancer risk with the administration of the anti-IL1β agent canakinumab. Despite small numbers and the need for prospective validation, the findings are exciting as they demonstrate the potential for personalized chemoprevention approaches. Such personalized approaches can potentially enhance the feasibility of cancer prevention trials. See related article by Woo et al., p. 429.