Ferlay, J. et al. Cancer statistics for the year 2020: an overview. Int. J. Cancer https://doi.org/10.1002/ijc.33588 (2021).

Article  PubMed  Google Scholar 

World Health Organization. Global health estimates 2020: deaths by cause, age, sex, by country and by region, 2000-2019. World Health Organization http://who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death (2020).

Independent UK Panel on Breast Cancer Screening.The benefits and harms of breast cancer screening: an independent review. Lancet 380, 1778–1786 (2012).

Article  Google Scholar 

Field, J. K. et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Reg. Health Eur. 10, 100179 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Lin, J. S., Perdue, L. A., Henrikson, N. B., Bean, S. I. & Blasi, P. R. Screening for colorectal cancer: updated evidence report and systematic review for the US preventive services task force. JAMA 325, 1978–1998 (2021).

Article  PubMed  Google Scholar 

World Health Organization. WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. World Health Organization https://iris.who.int/bitstream/handle/10665/94830/9789241548694_eng.pdf (2013).

NORC at the University of Chicago. Percent of Cancers Detected by Screening in the U.S. https://cancerdetection.norc.org/ (2022).

White, T. & Algeri, S. Estimating the lifetime risk of a false positive screening test result. PLoS ONE 18, e0281153 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wan, J. C. M. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17, 223–238 (2017).

Article  CAS  PubMed  Google Scholar 

Dudley, J. C. et al. Detection and surveillance of bladder cancer using urine tumor DNA. Cancer Discov. 9, 500–509 (2019).

Article  CAS  PubMed  Google Scholar 

Mouliere, F. et al. Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients. EMBO Mol. Med. 13, e12881 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, Y. et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci. Transl. Med. 7, 293ra104 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Markar, S. R. et al. Assessment of a noninvasive exhaled breath test for the diagnosis of oesophagogastric cancer. JAMA Oncol. 4, 970–976 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Leon, S. A., Shapiro, B., Sklaroff, D. M. & Yaros, M. J. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 37, 646–650 (1977).

CAS  PubMed  Google Scholar 

Kopreski, M. S., Benko, F. A., Kwak, L. W. & Gocke, C. D. Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin. Cancer Res. 5, 1961–1965 (1999).

CAS  PubMed  Google Scholar 

Papsidero, L. D., Wang, M. C., Valenzuela, L. A., Murphy, G. P. & Chu, T. M. A prostate antigen in sera of prostatic cancer patients. Cancer Res. 40, 2428–2432 (1980).

CAS  PubMed  Google Scholar 

Bast, R. C. Jr. et al. Monitoring human ovarian carcinoma with a combination of CA 125, CA 19-9, and carcinoembryonic antigen. Am. J. Obstet. Gynecol. 149, 553–559 (1984).

Article  PubMed  Google Scholar 

Kahlert, C. & Kalluri, R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J. Mol. Med. 91, 431–437 (2013).

Article  CAS  PubMed  Google Scholar 

Ashworth, T. R. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Med. J. Aust. 14, 146–147 (1869).

Google Scholar 

Bronkhorst, A. J. et al. Towards systematic nomenclature for cell-free DNA. Hum. Genet. 140, 565–578 (2021).

Article  CAS  PubMed  Google Scholar 

Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen, S. Y. et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 563, 579–583 (2018).

Article  CAS  PubMed  Google Scholar 

Neal, R. D. et al. Cell-free DNA-based multi-cancer early detection test in an asymptomatic screening population (NHS-Galleri): design of a pragmatic, prospective randomised controlled trial. Cancers 14, 4818 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lennon, A. M. et al. Outcomes following a false positive multi-cancer early detection (MCED) test: results from DETECT-A, the first large, prospective, interventional MCED study. Cancer Prev. Res. 17, 355–359 (2024).

Article  CAS  Google Scholar 

Rampinelli, C. et al. Exposure to low dose computed tomography for lung cancer screening and risk of cancer: secondary analysis of trial data and risk-benefit analysis. BMJ 356, j347 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Berrington de González, A. et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch. Intern. Med. 169, 2071–2077 (2009).

Article  PubMed  Google Scholar 

Morin, S. H. X. et al. Incidental findings in healthy control research subjects using whole-body MRI. Eur. J. Radiol. 72, 529–533 (2009).

Article  CAS  PubMed  Google Scholar 

Park, J. H. et al. Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population. J. Clin. Oncol. 41, 3069 (2023).

Article  Google Scholar 

LeeVan, E. & Pinsky, P. Predictive performance of cell-free nucleic acid-based multi-cancer early detection tests: a systematic review. Clin. Chem. 70, 90–101 (2024).

Article  CAS  PubMed  Google Scholar 

Wade, R. et al. Multi-cancer early detection tests for general population screening: a systematic literature review. Health Technol. Assess. 29, 1–105 (2025).

Article  PubMed  PubMed Central  Google Scholar 

Sorenson, G. D. et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol. Biomarkers Prev. 3, 67–67 (1994).

CAS  PubMed  Google Scholar 

Diehl, F. et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc. Natl Acad. Sci. USA 102, 16368–16373 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stroun, M., Anker, P., Lyautey, J., Lederrey, C. & Maurice, P. A. Isolation and characterization of DNA from the plasma of cancer patients. Eur. J. Cancer Clin. Oncol. 23, 707–712 (1987).

Article  CAS  PubMed  Google Scholar 

Forshew, T. et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci. Transl. Med. 4, 136ra68 (2012).

Article  PubMed  Google Scholar 

Newman, A. M. et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat. Med. 20, 548–554 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wan, J. C. M. et al. Liquid biopsies for residual disease and recurrence. Med 2, 1292–1313 (2021).

Article