Understanding age and sex differentials in cancer incidence and mortality: An international population-based study

Most epidemiologic analyses of male-to-female (M:F) ratios for cancer incidence have done so to gain aetiological understanding, focusing on age-standardized M:F rate ratios for specific cancer sites. None have quantified the extent and timing, with respect to age, of sex differentials in the total cancer burden (all sites excluding non-melanoma skin cancer). In the present study, using data from IARC's Cancer Incidence in Five Continents for 2013-17 (N = 60 countries) and GLOBOCAN mortality 2022 (N = 69), we estimated ages when the sex ratios peaked and reversed from a male to a female excess, or vice versa. Across all countries included, a common 4-period pattern was observed. For incidence, period 1 featured an early-life male excess up to age 21 years (region-specific means ranged from 18- to 24), followed by a period 2 multi-fold female excess lasting until age 59 (56-65) and peaking at a F:M of 2.4:1 (2.0-2.9) at age 41 (39-47), then period 3 with a large male excess peaking at M:F of 1.5:1 (1.2-1.6) at 73 (69-85) years. For the absolute burden alone (not rates) countries with long life expectancies experienced a 4th period of a female excess of cancers/cancer deaths at ≥85 years. These patterns were also present for mortality, but with a shorter period 2 duration. In summary, this study characterizes the four age periods of alternating sex differentials in the cancer burden, providing essential information to support sex-appropriate allocation of cancer prevention and oncology resources.