Worldwide over one million AYAs aged 15–39 years were diagnosed with malignant cancer in 2012 based on GLOBOCAN [4] (Table 2.1), which is 7 % of the 14.1 million new cancer cases of all ages worldwide estimated by GLOBOCAN for the same year [23].

The mix of malignant tumors in AYAs differs from that for all ages combined and from that in both younger and older persons. For all ages and both sexes, the top five cancers worldwide in 2012, in order of incidence, were cancer of the lung (13 %), breast (12 %), colorectum (10 %), prostate (8 %), and stomach (7 %) [23]. For AYAs, the order for the same year was breast cancer (18 %), cervix uteri cancer (11 %), thyroid cancer (8 %), leukemia (6 %), and central nervous system (CNS) tumors (4 %) (Table 2.2). In the United States, the predominant cancers in AYA males and females differ from the worldwide sequence in that, for the year 2012, the order was thyroid carcinoma (16 %), breast carcinoma (15 %), melanoma (9 %), cervix uteri carcinoma (7 %), and colorectal carcinoma (6 %).

Figures 2.2 and 2.3 illustrate with the United States data how the cancer mix in AYAs is highly age dependent within the AYA age span, as the cancers of childhood transit to those in adulthood (Fig. 2.2). From the youngest AYAs to the oldest, the incidence of breast cancer increases from extremely rare to the most frequent cancer. Cancer of the female genital tract (cervix, uterus, vagina, vulva) undergoes a similar increase. Leukemia on the other hand decreases from the most frequent type in children to a few percent in the oldest AYAs. When considered as a proportion of all cancer (Fig. 2.3), at least seven cancers have their highest percentage within the AYA age range: thyroid cancer, Hodgkin lymphoma, testis cancer, osteosarcoma, Ewing tumor, and Kaposi sarcoma. More than half of the cancers in AYAs are accounted for by those that peak in proportion during the AYAs years, further rendering the array of cancer types unique to the age group.

Nearly two-thirds of the incident cases were in females because the most common cancers in this age group are female-specific tumors (cervix uteri and other female gynecologic malignancies) or sites where the rates among females are much higher than for males (breast and thyroid) (Table 2.2). The most common cancer site for ages 15–39 years was female breast cancer with nearly 192,000 cases worldwide in 2012. The second most common was cancer of the cervix uteri and third was cancer of the thyroid, with 112,000 and 84,000 cases, respectively (Table 2.2). In AYA males, the most common was the leukemia, with 35,000 cases worldwide in 2012, followed by testis cancer and liver cancer with 34,000 and 33,000 cases, respectively (Table 2.2).

A broad grouping was used as a first cut of MDR. Since the populations of the LDR are so much greater than the MDR, it is expected based on GLOBOCAN estimates that more than two-thirds of the cases among 15–39-year-olds will reside in LDR, while the incidence rate is lower in LDR than MDR (Table 2.1).

Worldwide, the cancer incidence rates for AYAs vary from country to country and continent to continent. Figures 2.4 and 2.5 show, for males and females, respectively, the higher rates of total invasive cancers for North America (N America) (United States and Canada) and Northern, Western, and Southern Europe (N, W, S Europe) compared to the overall world rate of Central and Eastern Europe (C and E Europe), South America (S America), Asia, and Africa. While the overall cancer rates for N America and N, W, S Europe are similar, there are differences by site. In males, colorectal and renal cancer and leukemia and thyroid cancers are higher in N America, and melanoma and testicular cancer are higher in N, W, S Europe. The high rate in males of Kaposi sarcoma (KS) in Africa is in sharp contrast to the almost nonexistent KS rate in Asia and C and E Europe. Liver cancer is higher in Africa and Asia than in Europe (N, W, S and C and E Europe) and N America. In contrast, leukemia incidence rates in males are much lower in Africa than the other countries. Testicular cancer is much higher in N America and N, W, S Europe than in other regions. The incidence of nasopharyngeal cancer is higher in Asia than in any other regions.

For females (Fig. 2.5), the AYA breast cancer rates are similar between N, W, S Europe and N America, but nearly double those for the other regions. The rates for cancer of the cervix uteri range from a low of 6.7 in N America to a high of 14 per 100,000 females in S America and C and E Europe where it is the number one cancer among AYA females. The cervical cancer rates for N, W, S Europe are lower than for C and E Europe. However, in North Europe, cervix cancer incidence is also high in the Baltic countries which are included in the N, W, S Europe (data not shown). Thyroid cancer among AYA females in N America has more than double the rate of any other group of countries, and the thyroid cancer rate in Africa is one-twentieth that of N America. For females, N America has the highest rates for cancers of the colorectum, corpus uteri, and kidney and leukemia and NHL. S America has the highest rate for cancers of the ovary and the second highest rate for corpus uteri. While the KS rate among African females is lower than that for African males, the rate for African females is much higher than in the other country groups. Melanoma is higher in N, W, S Europe and N America and very low in Asia and Africa. For AYA females, nearly half of the cancers are breast or thyroid in N America and breast or cervix in C and E Europe, S America, Africa, and Asia. While Asia has the lowest breast cancer rate, breast cancer comprises nearly 30 % of the cancer burden among AYA females.

Since GLOBOCAN data are not available in finer age breakdowns than 15–39 years of age, SEER data were used to show how the cancer sites can vary across the age groups comprising the AYA group. Figure 2.6 shows the incidence rates for males and females by single years of age. After the childhood cancer peak between 2 and 4 years of age, the incidence decreases until age 8 in girls and 10 in boys and then increases exponentially until age 60 after which the increase slows until it plateaus after age 80. In females, the incidence is a smoothly exponential phase from age 10 to 50, whereas in males it is triphasic with separate exponential phases from age 10 to 25, 25 to 40, and 40 to 60. Males have a higher incidence from infancy to age 20 and after age 55, whereas females have a distinctly higher rate in between and particularly during the older AYA years.

For ages 15–39 years, the overall cancer incidence rate increases with each 5-year age group from around 20 (ages 15–19) to 130 (ages 35–39) per 100,000 (Fig. 2.7). The rates for the 35–39-year-olds are much higher than the rates for other age groups for males and females. The rates for children under 15 years of age are less than the 15–19 age group and for those 40 and over are much greater (notice the scale break) than the 35–39 age group. For males (Fig. 2.8), the incidence rates range from less than 25–90 per 100,000 compared to a range of less than 25 to over 170 per 100,000 for females. For the older AYA age groups especially 35–39 years, the overall rates for males (Fig. 2.8) are lower than that for females (Fig. 2.9). Even though breast cancer is predominately a cancer for females, it remains the cancer with the highest rate for both males and females combined and females alone for the 35–39-year age group. The increase in the breast cancer rate across the female age groups is dramatic, and it ranges from 0.2 for ages 15–19 to 60.1 per 100,000 for females aged 35–39 (Fig. 2.9).

In order to portray the incidence rates and trends more graphically, broader groups of sites were used in Figs. 2.7, 2.8, and 2.9. For males, genital (mostly testicular) cancer predominates for most age groups (from 20 years onward) except age group 35–39 in which three sites (lymphoma, male genital, and melanoma) dominate the picture.

For males aged 15–19 years, more than half of the cancers are leukemia, lymphoma, or genital tumors with corresponding rates of 3.6, 5.2, and 3.7 per 100,000. For males, the colorectal cancer rates increase from less than 1 per 100,000 for ages 15–19 to nearly 10 per 100,000 in 35–39-year-olds. Similarly, there is a large increase in cancer risk for melanoma between ages 15–19 and 35–39. Invasive CNS tumor rates and leukemia rates varied between 2 and 4 per 100,000 across all AYA age groups.

In proportional terms, breast cancer alone comprises 35 % of all female cancers in the 35–39-year age group and together with thyroid and genital cancers comprise over half of the cancers in this age group. Breast cancer is very rare for 15–19 (0.2) in comparison to 60 per 100,000 for ages 35–39. Large increases in rates across the age groups were seen for melanoma and cancers of the thyroid, genital tract, and colorectum.

Figure 2.10 shows the incidence rates for ages 15–39 combined by sex for a detailed list of over 25 cancer sites. Based on US SEER data, breast cancer is the number one cancer among AYA females with a rate of nearly 21 per 100,000, which is more than double the highest rate among males, cancer of the testis (10.17 per 100,000) (Fig. 2.10). For females, thyroid and melanoma complete the top three and for males, melanoma and NHL complete the top three. Cancer among AYAs is relatively rare with only female breast cancer, female thyroid cancer, and cancer of the testis with rates over 10 per 100,000 females/males.

Figure 2.11 depicts for American AYAs the average annual percent change (APC) during 2000-2011 of the incidence rate of cancer and of 28 individual types of cancer for females and for males. The average was 1 % per year in females and 0.25 % per year in males. For females, about half of the cancers show decreasing incidence trends and half show increasing trends. For males, more cancers decreased than increased in incidence. Lung and cervix uteri showed the largest decreases for females, whereas Kaposi sarcoma, anus, eye, and urinary bladder had decreases of more than 2 % per year for males. Two cancers, those of the kidney and thyroid, have had disproportionately greater increases in both females and males. For kidney cancer, the increases were 6.1 % and 5.8 % per year in males and females, respectively. For thyroid cancer, the corresponding rates were 5.1 and 4.7 % per year. In the United States, the cancers with the greatest increase during 1975–2011 among the oldest AYAs, those 35–39 years of age, were cancer of the thyroid, kidney, anorectum, and prostate (Fig. 2.12), the last a previously unreported finding. In females, the thyroid cancer increase accounts for most of the total increase, 61 % of the total during 1975–2011 and 83 % of the total during 2000–2011.

Table 2.3 lists the 5-year relative survival rates for the United States (SEER) and Europe by diagnostic group for each of the 5-year AYA age groups (15–19, 20–24, 25–29, 30–34, 35–39). To better understand the composition of the overall rates, the site distributions by age are presented in Table 2.4. Table 2.5 contrasts the survival for children (<15 years) and AYAs (15–39 years combined) by geographic area and is limited to site/histology groups affecting both AYAs and children. In contrast, Table 2.6 displays survival rates limited to carcinomas affecting AYAs (15–39 years) and adults (40–69 years). Obviously not all possible cancers are displayed in each table; the totals, however, include all cancers in that age group.