Current guideline-recommended screening

USPSTF guidelines recommend screening for breast (mammography), cervical (cytology and high-risk human papillomavirus) and colorectal (multiple tests in use including faecal DNA test and colonoscopy) cancer based on age alone, and lung cancer screening using low-dose computed tomography for adults aged 55–80 who have ≥ 30 pack-year smoking history and currently smoke or have quit within the past 15 years [9, 19–22]. In the US, multiple screening tests are available for colorectal screening, and we use the combination faecal immunochemical test (FIT)-DNA test (FIT-DNA) as the base case, having intermediate sensitivity and specificity compared to other tests. The UK breast and cervix cancer screening recommendations are the same as in the US [23], and FIT testing is often used for colorectal screening. Published national estimates of screening uptake (proportion of eligible individuals in the population who are screened) in both countries were used [11, 24], and also screening performance (sensitivity and FPR) for each test [19–24] [sensitivity: proportion of people with cancer who have a positive test; FPR: proportion of people without cancer who have a positive test, but for cervical screening a false positive is when a woman has colposcopy but no underlying CIN 2 or 3 or invasive cancer]. In general, test performance was assumed to be equal in both the US and UK, but the reported false-positive rate for mammography for the UK was taken from the UK Breast Screening Programme (2.8%) [25]. The estimates of uptake of breast and lung cancer screening we used for the US tended to be higher than reported in some studies, and we assumed all women had annual mammography (as indicated by the American Cancer Society for some age groups, while USPSTF recommend biennial screening). This was done to increase the number of cancers found by current screening, which reduces the number available to be detected by MCED testing (thus making outcomes and costs less favourable for MCED testing). The number of cancers detected by current guideline-recommended screening was computed by multiplying the number of cancers covered by each screening type, the adherence to that screening guideline, and the sensitivity of the screening modality. This approach assumes any interval cancers among cancers with a current guideline-recommended screen are only due to gaps in adherence or the sensitivity of the screening modality.