Improvements in modern treatments and diagnosis has led to reductions in incidence and mortality attributed to many neoplasms, including those that commonly occur among AYAs [5
]. However, incidence is still increasing for some cancers that commonly occur among AYAs and decline in mortality has lagged for certain cancers. This is the first study to have comprehensively investigated cancer incidence and mortality trends at the whole population level for a broad range of cancers that commonly occur among Australian AYAs aged 15–39 years using the adolescent and young classification scheme.
Increases in incidence rates were observed for testicular cancer, thyroid cancer, and ALL among male AYAs, whereas in young females, the incidence of HL, breast, and colorectal cancers increased over the 26-year study period. Decreases in the incidence of lung cancer and CNS tumors were observed among males only, cervical cancer among females, and melanoma for both the sexes. Between 1982-2005, cancer mortality rates decreased for both sexes, although considerable disparity existed between males and females by cancer type.
Despite expanding knowledge on many AYAs cancers, the reasons for the increasing incidence of some cancers are still poorly understood, particularly for testicular cancer [9
]. Known risks factors for testicular cancer include cryptorchidism, testicular atrophy and maternal exposures [10
]. Exposure to ionizing radiation, particularly in childhood, may influence the incidence of thyroid carcinoma later in life [12
]. However, the sex differential observed among AYAs in this study is not clear, although it may imply a specific susceptibility gene hormone receptor in the pathogenesis of thyroid carcinomas or possibly due to a greater medical surveillance in young women. Some of the increase in the incidence of thyroid cancer may be also explained by the use of improved diagnostic tests, although diagnostic scrutiny alone is unlikely to explain the trends observed in this study. Decreasing exposures to infections in childhood and thereby increased susceptibility later in life may play a role in the occurrence of both ALL and HL in adolescence and young adults. In fact, Epstein Barr virus, in particular, may play a role in the incidence of a substantial proportion of HL cases [13
There was a small but significant increase in breast cancer incidence. This may be a result of recent improvements in diagnostic imaging of the dense fibroglandular breast in young women and adjuvant chemotherapy and radiation therapy. Other potential contributing factors may include use of oral contraceptives and changes in the fertility patterns [14
]. Fortunately, breast cancer mortality among young WA women decreased over the same period. In fact, this group experienced the greatest decrease in mortality in this study, particularly post 1996. This is likely due advances in newer imaging techniques, such as magnetic resonance imaging (MRI), that can detect tumors previously occult because of the dense fibroglandular breast in young women. The recent reduction in the financial barrier through a Medicare rebate for MRI fee for young women <50 years of age and at high risk of breast cancer has the potential to further decrease mortality in this population.
The overwhelming majority of lung cancers in AYAs are caused by tobacco smoking. Tobacco control is currently a priority in Australia, with WA seen as the national leader in this area [15
]. Smoking prevention and cessation programs are aimed not only at the general population, but are increasingly targeting young people. However, while there has been some recent evidence of a decreasing trend in both incidence and mortality among men [16
], the situation in women, particularly young women, is a cause for concern. The present study results indicate that young women are not experiencing the same decline in lung cancer incidence as young men, which is consistent with known disparity of historical smoking uptake and cessation trends between genders [17
]. Nonetheless, it is expected that recent declines in female smoking rates would eventually result in a decline in the future incidence and mortality for AYA females [19
Colorectal cancer is uncommon among younger AYAs but rises substantially after the age of 25 years [20
]. The incidence of colorectal cancer increased for young females in our study, but not in males. Yet, hereditary predisposition, the main risk factor in this age group is expected to be similar in both sexes [21
]. Sex hormones have immuno-modulatory effects and may differentially affect the incidence of colorectal cancer in AYAs [22
]. However, the observed trend in incidence among females in our study is more likely to be attributed to environmental factors, such as changes in nutrition, smoking and alcohol consumption [21
], although these factors could not be evaluated in our study [21
]. Overall, mortality due to colorectal cancer has decreased substantially in the last decades. Recognition of familial colorectal cancer syndromes and refinement of diagnostic techniques are likely to have contributed to reductions in mortality among AYAs.
Trends in incidence and mortality of both cervical cancer and melanoma are largely influenced by earlier cancer detection and improved treatments. Cervical cancer screening to detect potentially pre-cancerous changes which are usually caused by sexually transmitted human papillomaviruses (HPV) infection is likely responsible for the decreases in incidence and deaths observed in our study. The recent implementation of the HPV immunization program in Australia, in 2007, is likely to further reduce the burden of cervical cancer. In WA, the spread of independent skin cancer clinics might have initially increased the incidence of cutaneous melanomas as result of increased detection of indolent cases through increased surveillance [25
]. The rise seems to have reversed more recently, possibly as a result of changes in recreational behavior and increased protection from sun exposure [26
]. Continued skin awareness campaigns are likely to further decrease incidence and mortality due to melanomas.
The overall pattern of increasing incidence [27
] and decreasing mortality [31
] of AYA cancers reported in this study approximates that observed in other developed countries, including in the United States, Canada and some western European nations. Increasing incidence of specific cancers such as thyroid [33
], testicular [36
] observed in this study population appears to be consistent with results from other AYA populations. The emerging lung cancer epidemic observed among females in our study is also consistent with other studies from several developed countries [38
]. Cervical cancer incidence and mortality rates continued to decrease among AYAs in WA and other developed countries [42
], although declines seem to be moderating or plateauing in some populations [44
A strength of this study is its use of routinely-collected, whole-population data from the WADLS, which has undergone extensive validation with false-positives and false-negatives shown to be <1% [46
]. Using these data, we investigated incidence and mortality trends over a 26-year period for AYAs aged between 15-39 years, and this is the first comprehensive analysis of cancer incidence and mortality trends among for a broad range of cancers that commonly occur among AYAs in Australia. Although WA’s population of 2.3 million is not very large, WA population is representative of the rest of Australia; it is closest to the average of the eight Australian states and territories with respect to: median age; distribution of sex, people living in remote areas, income, per capita health expenditure and hospital bed supply. In addition, the relatively low and stable overseas and internal migration (~2%) of the WA population has the advantage of reduced loss to follow-up. These characteristics of WA and the completeness of our data strengthened our study.
However, a number of challenges exist, particularly in the interpretation of results for rare cancers. Random fluctuations may erroneously appear as noteworthy trends and, therefore, care must be exercised in interpreting the trends for these cancers. Multiple comparisons were adjusted to ensure an overall type I error rate of 0.05 through the joinpoint permutation test. However, spurious associations are still possible due to the large number of statistical tests conducted. Important sub-population trends may have been obscured, given the epidemiological heterogeneity of the study population, particularly its broad age range and ethnic diversity, and the potential for interaction of these with both the spectrum of cancers identified and health service utilisation. In addition, AYA cancers represent a heterogeneous group of diseases with specific etiologies. Nonetheless, the observed differences in the trends between the sexes and across cancer subgroups provide starting points for etiologic research. Testable hypotheses, including individual characteristics and environmental exposures, can be investigated in relation to specific cancers through further rigorous study designs.