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Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.

BACKGROUND: Early detection of HPV-associated oropharyngeal squamous cell carcinoma, the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. HPV circulating tumor DNA (ctDNA) is a sensitive and specific biomarker for HPV-associated oropharyngeal squamous cell carcinoma at diagnosis. It is unknown if ctDNA HPV is detectable prior to diagnosis, and thus its potential as an early detection test is also unknown. METHODS: Plasma samples from the Mass General Brigham Biobank collected 1.3-10.8 years prior to diagnosis from HPV-associated oropharyngeal squamous cell carcinoma patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multifeature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay. RESULTS: HPV ctDNA results were positive in 22 of 28 prediagnostic samples from HPV-associated oropharyngeal squamous cell carcinoma cases (sensitivity 79%) with a maximum lead time of 7.8 years. HPV ctDNA results were negative in all controls (0 of 28, 100% specificity). Diagnostic accuracy was highest within 4 years of cancer diagnosis and was higher than HPV Ab detection within the same timeframe (P = .004). Application of a machine-learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27 of 28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years. CONCLUSIONS: HPV ctDNA can be detected in the blood years prior to diagnosis with HPV-associated oropharyngeal squamous cell carcinoma, with high specificity, in a case-control cohort of 56 participants. HPV ctDNA detection alone, or in combination with previously identified serological biomarkers, may be a feasible approach to early detection of HPV-associated oropharyngeal squamous cell carcinoma.

Humans

[Diagnosis of cancer and early detection. Clinical methods].

The etiology of cancer--as one of the most important causes of death--remains unknown. Therapy seems promising only in its early stages and if the exact diagnosis of carcinoma is possible. Diagnostic procedures today have gained a high standard demonstrated on malignancies of the gastrointestinal tract and the lung. The whole spectrum of methods can be employed only after having selected the patients according to "high risk" groups and methods of early cancer detection respectively. Effective and pragmatic progress has been made but is not fully utilized yet. Future trends in the diagnostic development are discussed.

Adult

[Early cancer detection in the oro-pharyngo-laryngeal area: analysis of a regional screening project (author's transl)].

During a six months lasting screening project 6866 persons were examined free of cost. Inspection of the mouth, endoscopy of the naso-hypopharynx and larynx with the Wolf-endoscope after v. Stuckrad, and palpation of the neck were included. Every sixth person required further diagnosis or treatment. Precanceroses were found in almost 3%, and up to now malignomas were found in 0.3% of the screened persons. Among these 14 cases of cancer were 9 carcinomas of the larynx. This comparatively high percentage of precanceroses and cancer favors the endoscopic screening of patients with organ-related symptoms and of high risk groups.

Adult

Beyond mutations: epigenetic and fragmentomic landscapes of cfDNA in lung cancer.

INTRODUCTION: Lung cancer is the most frequently diagnosed cancer worldwide and the leading cause of cancer-related mortality. Cell-free DNA (cfDNA) has emerged as a powerful biomarker in cancer detection. Early diagnostics efforts often leverage cancer-associated mutations present in cfDNA, but beyond such mutation-based assays, recent advances have shed light on other non-mutational features. The analysis of cfDNA epigenetic profiles and fragmentation patterns, known as 'fragmentomics,' has revealed a wealth of data to explore in noninvasive lung cancer diagnosis. AREAS COVERED: This review will explore this new narrative, summarizing the current understanding and use of cfDNA epigenetic modifications and fragmentomic patterns, while integrating findings to illustrate their vast potential in early-stage detection and therapeutics. By considering a range of epigenetic and fragmentomic features, cfDNA methylation (5mC, 5hmC), histone modifications, size profiles, and end signatures, this review highlights how the multidimensional integration of such signals shows promise in refining early-stage lung cancer and guiding therapeutic decisions. EXPERT OPINION: cfDNA epigenetic and fragmentomic analyses represent a transformative frontier in lung cancer diagnostics and monitoring. While these approaches demonstrate significant potential, most studies are limited by modest cohort sizes and reports of survival benefits, underscoring the need for large-scale validation and deeper mechanistic understanding.

Humans

Detecting early colon cancer.

Techniques enabling detection of early colon cancer already exist, but to be more productive in terms of improving survival they must be applied in a meaningful sequence and repeated regularly in high-risk patients. Positive findings in specific screening steps based on well-known risk factors in colon cancer always call for aggressive follow-up. The advantages and disadvantages of the various techniques are discussed.

Barium Sulfate

Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium.

Individuals with hereditary cancer syndromes are born with germline genetic variants that significantly increase their lifetime risk of developing multiple cancers. Cancer rates and overall mortality can be reduced with intensive surveillance to facilitate early cancer detection. However, participating in diagnostic imaging and endoscopy surveillance programs is often time-consuming, overwhelming, inconvenient, and anxiety-inducing. To improve this, multi-cancer early detection tests are being developed using cell-free DNA (cfDNA) sequencing analysis to detect cancers with more sensitivity than conventional screening methods. Our community (the CHARM consortium: Cell-free DNA in Hereditary And high-Risk Malignancies) has been exploring the use of cfDNA sequencing in hereditary cancer, and has launched the CHARM2 prospective randomized controlled trial, which is enrolling 1000 participants with Hereditary Breast and Ovarian Cancer, Lynch syndrome, Li-Fraumeni syndrome, Neurofibromatosis type 1 and Hereditary Diffuse Gastric Cancer to improve equitable access, early detection and surveillance for high-risk individuals. All participants will have screening as per conventional syndrome-specific surveillance recommendations. Half the participants (experimental cohort) will also have cfDNA analysis at least three times a year, with abnormal results triggering dedicated clinical imaging and diagnostic evaluation, and heightened surveillance. Vetted by our patient advisors, validated patient-reported outcome and experience measures assessing participant psychosocial outcomes, engagement, and test preferences will be administered to both arms. Our goal is to inform if and how cfDNA analysis could be implemented into routine clinical care and offer a path to equitable and more convenient cancer screening for all high-risk Canadians.

Female

Radiographic screening in the early detection of lung cancer.

A prospective study designed to detect early lung cancer in a high risk outpatient volunteer population is in progress. At present all 10,362 volunteers have been recruited into the project. A review of the radiographs of patients with lung cancer identified on the initial screen, or in retrospect, has led to the following conclusions: (1) Independent double reading is important in a screening project. (2) There are no reliable radiographic criteria to distinguish early lung cancer from benign disease. (3) The lateral chest radiograph is useful in the high risk patient. From these conclusions the authors have three recommendations for the practicing radiologist. (1) Since double reading improves sensitivity, attempt to doubly read a chest radiograph by removing your eyes from the film and look at it a second time before finalizing your report. (2) Consider any newly appearing, noncalcified lesion in the chest radiograph of a high risk individual as primary lung cancer until proven otherwise. (3) Consider the "routine chest radiograph" in a high risk patient as a challenge to detect early lung cancer rather than the drudgery of day to day clinical practice.

Aged

[Psychological aspects of the fear of cancer (author's transl)].

The fear of cancer was investigated in 423 women in our policlinic by means of a questionnaire. Psychological and sociological data, knowledge of the genital organs and experience of gynecological events were recorded. Of the women questioned, 16% said that they "often" feared suffering from cancer, 57% "sometimes" and 27% "seldom/never". The fear of cancer increased with age (P 5%). Women with higher education expressed fear of cancer more rarely (P 1%). The greater the knowledge of the genital organs, the less the fear of caner (P 5% and P 1%). Women with unpleasant experience or expectation of gynecological procedures frequently expressed fear of cancer. Of 12 with FPI recorded personality dimensions, 8 had a statistically significant relationship to fear of cancer. The fear of cancer had an effect on the attitude to investigation for early detection of cancer (P 10%) and to the curability of cancer detected early (P 1%).

Adult

Mass screening for early breast cancer detection.

In 1969 the Center for Social Diseases of Florence started a screening program for early breast cancer detection. The female population over 40 years of age of a group of outlying towns of the District was invited. From January 1969 till March 1977, 21,725 women have been examined in the program. Mammography was the diagnostic procedure of choice, followed by physical examination if necessary. Negative cases were controlled with biennial mammography. This paper summarizes and evaluates the results of this screening program. At first mammography, 67 cancers were detected, 37% of which were clinically unapparent, 62.3% staged T1A, and 52% N--. The average stage at diagnosis is certainly better than the average stage of cancers diagnosed in unscreened women, thus a better prognosis is expected. Actuarial survival rate of detected cancers was 94 +/- 3.7% at 5 years. False negative and false positive cases are reported. The possibility of hazards in the use of repeated mammography in mass screening is discussed. According to reported data the value of this screening program in terms of secondary prevention (early diagnosis) is confirmed.

Adult

Roentogenographic chest screening in the detection and survival of patients with lung cancer. Cooperative Study Group for Early Detection of Lung Cancer in the German Democratic Republic.

In the German Democratic Republic (GDR), annual mass roentgenographic screening of the chest was introduced twenty years ago. To ascertain its value in the detection of lung cancer, data were collected about treatment results at the country's main chest clinics. The study cover 13,283 operations and 10,838 resections, accounting for nearly 90% of all patients with lung cancer treated surgically in the GDR from 1949-1974. From 1965 to 1968, the five-year survival was more favorable in patients who were screened than in those who were diagnosed after clinical symptoms had appeared (36% for the former, 29% for the latter). For improvement of overall results, we recommend differentiated regular chest roentgenographic screening of men 40 to 70 years of age, individualized on the basis of tobacco usage, and full exploitation of all diagnostic and surgical tools now available.

Adult

Accuracy of chest film screening by technologists in the New York early lung cancer detection program.

A study of the feasibility of using specially trained radiologic technologists to screen chest radiographs was undertaken as part of an early lung cancer detection program. In their initial examination, 8,000 men had posteroanterior and lateral chest films which were prepared and evaluated by two specially trained technologists prior to interpretation by a radiologist. The technologists' accuracy in screening was subsequently assessed by comparison with the radiologist's interpretation and with clinical follow-up information. There were differences in the level of suspicion of the two technologists, but both were effective in selecting a subset of the screened population that contained the men with radiologically identifiable lung cancer.

Humans