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Professionals and public alike believe in the benefits of early cancer detection. Yet screening programs have encountered serious problems in engaging their clients to seek prompt medical follow-up. If benefits of early detection are to be achieved, and fear and mistrust overcome, a more reliable connection between screening and treatment must be forged.
DNA methylation is a critical epigenetic modification that regulates gene expression and plays a significant role in cancer development. This methylation signature can be detected in cancer-derived DNA from non-invasive samples, such as plasma, urine or Pap smears. However, in early-stage cancers-when detection is most critical-the concentration of cancer DNA is often low, limiting the sensitivity of current detection methods. Traditional DNA methylation detection techniques, which rely on methylation ratio-based measurements, may obscure subtle variations in methylation patterns, further reducing detection sensitivity. In this study, we analyzed cervical scraping specimens and examined whether detecting cancer-specific methylation patterns in cervical cancer could be enhanced using a Highly Methylated Haplotype (HMH) approach. This novel approach captures highly methylated haplotypes at single-molecule resolution using next-generation sequencing, providing greater detail than conventional methods. HMHs in specific DNA regions are a hallmark of cancer and stand out in contrast to sporadic methylation commonly observed in non-cancerous tissues. We applied HMH profiling to a gene panel of four biomarkers (CA10, DPP10, FMN2, and HAS1) previously validated in cervical cancer studies. At pre-specified cutoffs (99th percentile of normals), haplotype-based scoring achieved 89.9% sensitivity for invasive cancer at high specificity (~ 94-98%), outperforming median (78.0%) and single-CpG (71.6%) methods. For clinically relevant endpoints, the combined panel detected 51-52% of CIN2 + and 66-67% of CIN3 + cases, again exceeding the performance of median- and single-CpG-based scoring methods.These findings demonstrate the potential of HMH to substantially enhance sensitivity in cervical cancer detection, offering a promising approach for non-invasive diagnostics.
Approximately 8000 cigarette-smoking men over the age of 45 have entered into a lung cancer detection program in New York City. Cytologic examinations of sputum were carried out on 4000 subjects and lung cancer was found by this technique in nine men with normal chest x-rays. Seven had in situ or incipient invasive epidermoid carcinoma confined to the bronchus. These seven cases were studied by detailed histologic examinations of the bronchial tree in the resected specimens through sixth generation subsegmental bronchi. It was concluded that: 1) invasive epidermoid carcinoma arises from carcinoma in situ of bronchial surface epithelium or an extension of that neoplastic epithelium in bronchial glands; 2) the site of origin is a segmental bronchus in most instances; and 3) each carcinoma should be considered as unifocal in origin even though there is a continuing risk of another primary lung cancer. It seems unlikely that squamous metaplasia or basal hyperplasia is an essential step in carcinogenesis; rather, we believe that carcinoma may arise in bronchial epithelium without regard to the presence or absence of basal hyperplasia or squamous metaplasia, which should be considered nonspecific reactions to injury that may or may not accompany carcinogenesis.
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.
BACKGROUND: Early cancer diagnosis in patients with non-specific symptoms is limited by the lack of discriminatory tests. Within the Oxfordshire Suspected CANcer (SCAN) pathway, exploratory biomarker work showed that serum 1H NMR-based metabolomics can identify cancer with high accuracy. SCAN2 evaluated whether integrating metabolomics with glycomics provides complementary molecular information and improves discrimination in a clinically complex, real-world population. METHODS: Serum from 369 SCAN patients (59 cancers) was analysed using AXINON® System-derived NMR metabolomics and HPLC-MS glycomics. Machine-learning models were trained to predict cancer status, with performance assessed by receiver operating characteristic (ROC) analysis of pooled cross-validated predictions. To place cancer risk in a broader clinical context, a second classifier modelling alternative non-cancer diagnosis was incorporated, and mean predicted probabilities from both models were jointly projected into a two-dimensional space, maintaining strict separation of training and test data. FINDINGS: In the full cohort, integration of glycomics with metabolomics achieved an AUC of 0.814 (95% CI 0.808-0.820). In a refined sub-cohort excluding major comorbidities and selected cancer types (32 cancers, 277 non-cancers), performance improved to an AUC of 0.884 (95% CI 0.879-0.890). Discriminatory features included cancer-associated biantennary fucosylated glycans alongside amino acid metabolites (glutamate, histidine) and lipoprotein-related measures. A classifier distinguishing metastatic from non-metastatic disease (n = 29 vs. 30) achieved an AUC of 0.80. Joint probability analysis in the full cohort preserved cancer-associated signatures across comorbidity burden, with projection-based classification achieving an accuracy of 89.2% (95% CI 85.7-92.6). INTERPRETATION: These findings validate the SCAN1 metabolomic signature in a more clinically complex cohort and indicate that integrating glycomics with metabolomics provides complementary biological information for cancer discrimination. Joint probability analysis provides an interpretable framework for cancer risk stratification within multimorbid diagnostic pathways, supporting the clinical potential of scalable multi-omics blood testing. FUNDING: EPSRC, EU Horizon 2020, Wellcome/MLSTF, Novo Nordisk Foundation.
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Various biophysical methods have been utilized in the diagnosis of breast cancer. To date the best results have been obtained with x-ray mammography. Ultrasound and thermography have great appeal as non-destructive techniques but, in the present state of development, are of limited use. The spatial resolution presently obtainable in ultrasonograms is inadequate for the detection of subclinical cancer and thermography is also of questionable reliability. While an overall true positive rate of 70% to 75% may be anticipated with thermography, the bulk of false negatives would seem to occur in those tumors most amenable to therapy, i.e., subclinical cancers. The "false positive" rate of thermography is also excessive, but would be acceptable for establishing a high risk group if true positive rates could be improved. At present thermography finds its greatest use as an adjunct to mammography and physical examination; it should not be used as the sole modality in a screening program. The efficacy of mammography can be readily demonstrated but the propriety of its use as a screening device has been questioned. This is primarily related to the possible carcinogenic effect of radiation at diagnostic levels. Although the carcinogenic effect is unproven, the dose in radiologic procedures should be kept to a minimum consistent with adequate images. The present state of the art would indicate that the risk, if any, is minimal as contrasted with the natural incidence of breast cancer and the results of early diagnosis and treatment.
Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.
The records of the district offices for cancer control in Berlin and Königs Wusterhausen were used in order to analyse changes in the detection and management of female breast cancer between 1955 and 1974. The proportion of new cases younger than 45 years has increased from 8 percent to about 13 percent. Since 1970 there has been an increase in stage I and a decrease of stage IV. From 1960 to 1969 only 71 percent of all patients were radically operated upon, but in 1973/74 the proportion rose to nearly 75 percent. The tendency to extend the indication for radical surgery affects elderly women (65 to 74 years) more than younger patients. Survival rate depends on clinical stage, age and mode of treatment. It can be expected that the survival rate will increase with more radical surgery.
The family physician, more than most other physicians, is faced with rapidly increasing demands for breast cancer screening. The old standby, physical examination, is now accompanied by mammography, xeromammography, and, more recently, thermography. In this paper, we present our opinion, based on the collective experience at the Mayo Clinic, regarding the use and effectiveness of the several modalities, including mammography, xeromammography, and thermography, available for detection of breast cancer today.
In Berlin, capital of the G.D.R., more than 8,600 cases of bronchial cancer were observed in the period 1955 to 1969 and in 1973/4. Number of cases has increased from one 5-years period to the following period. Incidence of lung cancer in men increased especially in higher age groups whereas in female a rising incidence can be seen in all age groups. Duration of history is no good measure of health behaviour and of diagnostic quality. Distribution of clinical stages gives reliable information on the situation of detection. With rising age, the proportion of advanced stages increases. Stage distribution has not changed during the observation period and no measurable progress towards earlier detection of lung cancer has been achieved. In the same time, proportion of elderly lung cancer patients rose considerably and the chances of radical surgical treatment grew worse. Nevertheless the resection rate has increased. It seems that the quality of specialized surgical care has made some progress. Some conclusions can be drawn for cancer control: Prophylactic examinations are to be concentrated on high risk groups. Patients with suspicion of lung cancer shall be admitted to the specialist without delay. Development of nonsurgical methods of therapy for cancer of the lung is an important goal.
In Bucharest, district 6, of the 1 151 313 radiophotographies performed, 261 revealed bronchopulmonary cancers (22.6 per 10 000) of which 73% males and 27% females, the 50--70 years age group being the most affected (181 cases, i.e. 70%). The 85% deaths occurred within 2 years after detection. In 68% (177 cases) cancer was peripheral and in 32% centrohillar. The peripheral localization in 68% of the cases opens prospects for an early detection by dynamic follow up of the pulmonary radiophotography at shorter intervals, especially in the age group with a higher cancer risk (50--70 years), indicating in some cases immediate admission to a surgical department.
A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.
Peripheral blood leukocytes from patients with gastric cancer and various other malignant and nonmalignant diseases and peripheral blood leukocytes from apparently healthy volunteers were tested in the leukocyte migration inhibition test with the use of 4-5 different 3 M KCl extracts of gastric cancer tissue. An operational criterion for defining sensitization of patients' leukocytes was developed; i.e., evidence in an individual sample of leukocytes of either decreased or increased migration areas (migration index less than or equal to 0.79 and larger than or equal to 1.20, respectively) with 3 or more antigen extracts. With this as an indicator of sensitization, it was found that 91% of patients with gastric cancer (39/43), comparto 5% (5/94) and 3% (1/32) of patients with nonmalignant, nongastric diseases and normal controls, respectively, were reactive. Patients with various nongastric cancers were sensitized in 36% (49/135) of cases. Gastritis and gastric, as well as duodenal, ulcer did not influence the reactivity of patients' leukocytes, but considerable sensitization was found in patients with atrophic gastritis or intestinalization. When classified in the usual manner, i.e., by considering the reaction with individual tumor extracts, the specificity and the sensitivity of the test was markedly diminished: More false negative determinations were found in the group of gastric cancer patients, and the percentage of false positives in the group of nonmalignant diseases increased. The results gave evidence of tumor-associated antigens in gastric cancer patients, against which the host elicited a cellular immune response. The high incidence of positive reactivity of leukocytes from patients with gastric cancer, together with the considerable cross-reactivity of leukocytes from patients with nongastric cancer, pointed to the expression of antigens with organ-related and widespread specificities.
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The Mayo Lung Project was established to develop and evaluate a screening program for early lung cancer in high-risk subjects. Men who are more than 45 years of age and who smoke one package of cigarettes or more daily are screened by the use of thoracic roentgenograms, three-day pooled sputum cytology, and lung health questionnaires at four-month intervals. These data are compared with data from similar subjects screened only on entry into the project. During the past three years, 34 patients who had no roentgenoraphic evidence of lung cancer were identified and examined because of carcinoma cells in sputum. Of these 34 patients, 27 have had bronchoscopic localization of their tumors and definitive treatment and 3 had upper respiratory tract neoplasms and also have been treated. Of the remaining four, one patient died suddenly after myocardial infarction and three patients have not had localization or treatment because of other severe complicating medical problems. Localization of roentgenographically occult lung cancer is reliable by the use of bronchofiberoscopy and meticulous, thorough sampling from the tracheobronchial tree. A search must be made for upper airway cancers in the same high-risk population, and the possibility of second primary bronchogenic tumors also must be considered. Although follow-up is short, 22 of the 27 treated lung cancer patients were found with stage I disease. The outlook for 19 of these 27 is encouraging an average of 16 months after surgical resection.
Data from a Colposcopy Clinic have been presented in which endocervical and cervical smears were evaluated in singly and in combination for accuracy and effectiveness. In patients with marked dysplasia, carcinoma in situ and early invasive cancer, false negative results rarely occurred using either cervical or endocervical smears; more false negatives were encountered in the minimal to moderate dysplasia group of lesions. Endocervical smears were found to be unreliable in determining the distribution of cervical neoplasia when correlated with endocervical curettage specimens. These smears contributed little as supplemental screening procedures for early cervical neoplasia since less procedures for early cervical neoplasia since less than three per cent of lesions would have been missed had only a cervical scrape smear been performed. It should be pointed out, however, that this was a young population in which cervical eversion with exposure of endocervical tissue and the neoplastic lesions was the rule. The accuracy of endocervical aspiration and endocervical swab techniques was similar although there was a much higher proportion of unsatisfactory specimens with the dry cotton swab technique.
The incidence of stage A (incidental) adenocarcinoma of the prostate in transurethral resection (TUR) specimens is approximately 16%. This paper discusses the criteria for differentiating stage A1 versus stage A2 tumor, based on tumor volume and grade. Both the short-term (4 year) and long-term (8-10 year) natural history of untreated stage A1 prostate cancer are examined. Options to follow patients expectantly are presented. These include digital rectal examination and transrectal ultrasound. Specific problems relating to analyzing transrectal ultrasounds in patients who have had a prior TUR are addressed. Also, the unique aspects of transrectal ultrasound for stage A1 disease as it relates to the location of the lesion are expanded upon. The third option in the management of stage A1 disease is to monitor serum prostate specific antigen (PSA) levels. Areas covered include the sensitivity and specificity of PSA in general, and, in specific, serum PSA levels following TUR for stage A1 disease as a predictor of residual tumor. New data on a small group of patients who underwent delayed radical prostatectomy following diagnosis of stage A1 disease, where PSA data was available, are presented. The rationale for following patients with stage A1 disease by monitoring their serum PSA levels is supported by data from a group of men with normally sized prostates, benign prostatic hyperplasia, or cancer where longitudinal serum PSA levels were available. Finally, the option of radical prostatectomy for stage A1 disease is put forth. Data include a study of a large group of radical prostatectomy specimens performed for stage A1 disease.(ABSTRACT TRUNCATED AT 250 WORDS)