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

## TL;DR

This study reveals how cancer incidence and mortality rates differ between males and females across four distinct age periods globally.

## Contribution

The study identifies a consistent four-period pattern of sex-based cancer burden differentials across age groups using global data.

## Key findings

- A male excess in cancer incidence is observed in early life up to age 21.
- A female excess in cancer incidence peaks at age 41 and lasts until age 59.
- A male excess in cancer incidence peaks at age 73 and continues into later life.

## Abstract

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.

Cancer incidence and mortality differ between males and females. Whether these differences fluctuate across life stages, however, remains largely unknown. Drawing on worldwide cancer registry data and mortality estimates, this study explored age‐related differences in cancer occurrence between the sexes. Globally, cancer patterns show four phases: a slight male excess in childhood, a female excess in early to mid‐adulthood, a male excess in later life, and—where female longevity is high—a return to female excess at very old ages. Marked excesses in early cancer risk in females extend survivorship and the period of vulnerability to late treatment effects.