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

In the current landscape of clinical studies, the concept of statistically significant association is often mixed up with the expectation of improved prediction performance. We discuss the two concepts, association and prediction, and present the epidemiologic principles and statistical constructs that underlie the discrepancy between statistically significant associations and the rationale for their lack of impact on improving prediction in terms of discrimination. This issue is illustrated using an existing breast cancer dataset. The concept of statistically significant association should not be mixed up with the expectation of improved discrimination performance. Although some markers may not markedly improve discrimination, they can still have substantial clinical relevance by identifying critical biological pathways that inform novel treatment or prevention strategies. Development of models for both association and prediction assessments should be directly tied to clinical translation to move adoption forward to advance precision medicine.

Prevention relevance: Development of models for both association and prediction assessments should be directly tied to clinical translation to move adoption forward to advance precision medicine.

Although the majority of gastric cancer research has focused on the treatment of late-stage tumor masses, intervention at precancerous stages represents a far more amenable strategy to achieve long-term prevention of cancer. In contrast with preventative strategies focusing on lifestyle changes and nutritional alterations, few efforts have evaluated the ability to use short-term therapeutic interventions to reverse precancer and thereby reduce risk for developing cancer. The distinct advantage of this approach lies in the recognition that precancerous lesions are far more homogeneous with fewer, if any, driver mutations that can lead to therapy resistance. Our recent studies have demonstrated that a limited 2- to 4-week course of MEK inhibitor in rodent models, and now in a human phase I trial, reduced intestinal metaplasia and increased normal acid-secreting parietal cells in the gastric mucosa. These findings demonstrate the efficacy of targeting the precancerous metaplasia with limited duration treatments that allow recrudescence of normal gastric lineages. Further progress to bring these approaches to clinical utility will require a major change in the outlook of pharmaceutical companies and physicians for initiatives to target precancer.

This study examined trends in colorectal cancer screening modality utilization across the United States from 2016 to 2022, leveraging a large national claims database. The purpose was to identify national, regional, and demographic patterns in screening behavior during a period that encompassed the introduction of multitarget stool DNA testing (mt-sDNA) and the COVID-19 pandemic. Among 6.9 million colorectal cancer screenings analyzed, overall utilization increased through 2019, dipped in 2020 due to pandemic disruptions, and rebounded by 2022. Colonoscopy remained the dominant modality, with its utilization increasing in both relative and absolute terms. mt-sDNA testing experienced rapid adoption, increasing from less than 1% to 17% of all screenings, whereas fecal occult blood testing and fecal immunochemical testing declined. Multinomial logistic regression revealed that utilization patterns varied significantly by region, rurality, sex, age, and year. The Midwest and rural patients exhibited higher uptake of both colonoscopy and mt-sDNA compared with other groups, whereas the West maintained the highest reliance on fecal occult blood testing and fecal immunochemical testing. Findings highlight the nonuniform adoption of screening modalities across regions, urban and rural patients, categories of sex, and age cohorts. Understanding these patterns can inform and improve future resource allocation with the goal of increasing colorectal cancer screening uptake and adherence.

Prevention relevance: This study informs cancer prevention by revealing regional and demographic variation in colorectal cancer screening modality use. Understanding these evolving patterns can inform and improve targeted strategies and allocation of resources to improve screening uptake and adherence.

Health education can improve cervical cancer screening uptake; however, evidence from randomized controlled trials in the general population of Addis Ababa is limited. The aim of this study is to assess the effect of health education on screening uptake and knowledge among women aged 30 to 49 years in Addis Ababa, Ethiopia. A randomized controlled trial was conducted involving 1,300 women who had never been screened before. The intervention group received home-based health education about cervical cancer, supplemented by brochures. The χ2 test, independent sample t test, and paired t tests were used to assess pre- and pos-tintervention differences. The impact of the intervention was measured using the differences-in-differences approach. Three months after the intervention, 1,154 (88.8%) were interviewed. Screening uptake was significantly higher in the intervention group, with 241 (41.8%) of women screened compared with 93 (16.1%) in the control group. After the intervention, awareness increased by 42.2%, knowledge of symptoms increased by 23.1%, knowledge of risk factors increased by 15.2%, positive attitudes improved by 26.7%, and overall knowledge increased by 19.5% among the intervention group, indicating that the change is statistically significant. The differences-in-differences analysis indicated that 51% of the change in overall knowledge was due to the intervention. Age, occupation, and income were significantly associated with the uptake of screening, whereas the lack of time was a common barrier. Structured home-based education significantly increases cervical cancer knowledge and screening uptake. Scaling up home-based health education can significantly improve screening uptake.

Prevention relevance: Cervical cancer is the second leading cause of cancer-related morbidity and mortality among women in Ethiopia. Increasing awareness, improving access to screening, and promoting timely preventive interventions are critical to reducing the disease burden and increases life saving among women.

Germline and somatic alterations in the EGFR gene contribute to the pathogenesis and therapeutic response of non-small cell lung cancer (NSCLC). This retrospective single-center study analyzed 507 Azerbaijani NSCLC patients genotyped for EGFR mutations between 2009 and 2024. Real-time PCR identified somatic EGFR mutations in 137 cases (27.0%), while next-generation sequencing confirmed germline EGFR T790M variants in 11 patients (2.1%). Among these, nine carried concurrent somatic EGFR alterations and two harbored only germline variants; the latter are excluded from the present analysis and will be reported separately. All germline carriers had a positive family history of lung cancer. Germline carriers were more often diagnosed at early stages (I-II, 45.5% vs. 18.2% in non-carriers; p = 0.03), and four developed tyrosine kinase inhibitor (TKI) resistance within 6-8 months of treatment. Kaplan-Meier and Cox regression analyses revealed no significant survival difference between hereditary and somatic mutation groups (median OS 24.9 vs. 24.0 months; log-rank p = 0.69; HR = 1.19; 95% CI, 0.52-2.73). These findings indicate that germline EGFR T790M represents a measurable hereditary variant within the South Caucasus population and emphasize the need to integrate germline testing into diagnostic workflows and familial risk assessment strategies for EGFR-driven NSCLC.

Early detection efforts in gastric carcinoma (GC) focus on identifying those with gastric premalignant conditions (GPMC), as they may benefit from secondary prevention. Non-invasive identification of persons with GPMC is an ideal avenue, but currently, no such strategy exists. While persons with CagA (the most well-known virulence factor in Helicobacter pylori (HP) infection) may be more prone to GPMC, CagA has traditionally been limited to research settings. Recently, a novel point of care test for CagA was developed. Here, we report on the clinical utility of this test. We evaluated samples from adults undergoing pre-planned endoscopy between 2023-2025 for benign indications to evaluate the association between GPMC and CagA antibody positivity. Among 95 persons, we found that 40% had HP infection, 14% had GPMC, and 41% had CagA antibody positivity. There was a non-significant association between CagA antibody positivity and GPMC (OR 1.68, 95% CI: 0.48-5.85, p=0.42). In those without active HP, OR for CagA antibody positivity was 0.78, 95% CI: 0.13-4.73, p=0.79, while in those with HP, OR for CagA antibody positivity was 3.46, 95% CI: 0.29-41.52, p=0.33. We find non-significant associations between CagA antibody positivity and GPMC, and that active HP infection may represent an important effect modifier. Our data suggest that while larger scale validation is needed, a risk-guided screening strategy could include first, testing for active HP infection (e.g. breath or stool test), and if positive, POC testing for CagA antibodies.

While chemoprevention medications including selective estrogen receptor modulators and aromatase inhibitors are recommended for women at high-risk for breast cancer, their uptake remains low. In contrast, statin use for atherosclerotic cardiovascular disease (ASCVD) risk reduction is widely adopted. We conducted a retrospective cohort study amongst a population of women, age 40-79 who underwent screening mammograms at Columbia University Medical Center in 2014-2016. For each woman, we calculated breast cancer risk using the Breast Cancer Surveillance Consortium (BCSC) v3 risk calculator and ASCVD risk using the American Heart Association (AHA) risk calculator. High-risk using the BCSCv3 calculator was defined as ≥5% invasive breast cancer risk at 10-years and high-risk using the AHA calculator was defined as >7.5% ASCVD risk at 10-years. Average 10-year risk of invasive breast cancer was lower than that for ASCVD (2.47% vs 7.53%, p<0.001). Based on disease risk, 4.7% and 34.4% of participants met high-risk criteria for breast cancer and ASCVD, respectively. Chemoprevention uptake among women at high-risk for breast cancer was lower than statin uptake among women at high-risk for ASCVD (4.6% vs 72.9%). Numerous barriers likely contribute to this discrepancy in uptake including provider familiarity with and knowledge of chemoprevention, patient concerns for medication safety, absence of routine breast cancer risk assessment, and lack of intermediate biomarkers to monitor treatment response. Given the increased acceptance and uptake of statins relative to chemoprevention, there is potential value in putting chemoprevention in the context of statins to promote awareness and uptake.

Ovarian cancer is the leading cause of death among gynecological cancers due to its late diagnosis, but risk stratification for targeted prevention can improve outcomes. To identify women at risk of ovarian cancer, pathogenic variant testing is used, especially for those with a family history of the disease. However, high-risk genetic variants are rare, accounting for < 20% of ovarian cancer cases overall. More recently, clinical models that help identify ovarian cancer cases incorporate polygenic risk for improved risk stratification. Herein, we cross-validate a polygenic risk integrated clinical model called the refined risk model, in a nested case-control population from the Nurses' Health Study. The refined risk model is compared with a clinical risk score and polygenic risk score model respectively. The odds ratios per standard deviation were 1.26 (1.01, 1.48), 1.13 (0.96, 1.33) and 1.22 (1.04, 1.43) with corresponding AUCs of 0.56 (0.51, 0.61), 0.54 (0.49, 0.59), 0.55 (0.50, 0.60) for the refined risk, clinical risk, and polygenic risk models, respectively. Population screening has been assessed over the years, and while stage shifting in the screened population has occurred, the mortality benefit was not evident. However, as treatments for ovarian cancer improve, the benefits of a risk-stratified approach to screening are expected to grow.

Anal cytology and human papillomavirus (HPV) testing are the most common tools for anal cancer screening. We conducted an exploratory survey on the use of anal cytology in Italy. The Italian Society of Cytology (SICi) disseminated a questionnaire to its members and contacts on screened populations, departments collecting the samples, devices used, type of cytology (conventional or liquid based), professionals evaluating cytology, reporting system, use of anal cytology alone or in combination-test modality, diagnostic procedure for screen-positive individuals, and departments involved. Eighteen centers participated in the survey. In 15 centers (83.3%), anal cytology is performed on more than one at-risk population: men who have sex with men (MSM)/transgender women (TW) living with human immunodeficiency virus (LWH 13 centers, 72.2%), women with a history of gynecologic (pre)cancer (10 centers, 55.6%), women LWH (nine centers, 50.0%), men who have sex with women LWH, and MSM/TW not LWH (eight centers, 44.4%). Samples mostly come from infectious disease (nine, 50.0%) and sexually transmitted infection units (seven, 38.9%). A median of 140 samples (IQR, 30-500) are collected per year, with 13 centers (72.2%) using a cytobrush. Cytology is generally conventional (11 centers, 61.1%) and is mainly interpreted by histopathologists (66.7%) and biologists (55.6%). All centers use the Bethesda System for reporting cytology. Most of the centers use cytology in co-testing with HPV (10, 55.6%). Twelve centers (66.7%) perform high-resolution anoscopy, and the diagnostic procedure is frequently performed in general surgery (eight, 44.6%). Most of the centers employ anal cytology in people LWH and perform conventional cytology. Screening modality is variable, with more than half of the centers using cytology in co-testing with HPV. The use of high-resolution anoscopy is still suboptimal.

Prevention relevance: Screening for anal cancer prevention in Italy relies on heterogeneous and not fully satisfactory tools. Further efforts should be made to implement the optimal strategies in order to address the needs of the populations with the highest anal cancer risk.

Cervical cancer screening and its implementation have evolved tremendously since the first method, cytology using the Papanicolaou stain, was introduced in the 1950s. New screening methods, such as human papillomavirus testing, have been discovered, and evidence-based changes have been made to official screening guidelines set forth by various US organizations. With the advent of a human papillomavirus vaccine in 2006 and with more recent research into populations carrying disparate burdens of cervical disease, the effectiveness of current cervical cancer screening programs is being called into question as the disease incidence has not decreased as expected in the past 20 years. This review highlights where cervical cancer screening in the United States started, the current clinical methods, and promising developments on the frontiers of screening research to introduce new screening options or improve current screening programs and outcomes. We also highlight certain population factors that hinder effective screening in high-risk groups, based on research aimed at ensuring that population-wide screening continues to be an effective strategy for reducing cervical cancer incidence and mortality.