Late menarche, giving birth, breastfeeding, oral contraceptive use, IUD use, and tubal ligation decrease risk for both endometrial and ovarian cancer, while more ovulatory cycles, obesity, use of talc in genital hygiene, and late menopause increase risk. Despite these similarities, different explanations are proposed: estrogen excess for endometrial and incessant ovulation for ovarian cancer. Common pathways could include reproductive tissue turnover with accumulation of PTEN or p53 mutations or an immunebased explanation involving mucin proteins. Seeking unified explanations for risk factors common to both cancers could lead to new perspectives on how to prevent these common and lethal gynecologic cancers.
The epidemiology of ovarian cancer and endometrial cancer is closely entwined. Age-specific incidence curves and the international rates for both sites parallel each other, and histologic subtypes of cancer arising from the endometrium mirror types found in the ovary. Most of the personal factors that increase or decrease risk for one of these cancers act in the same direction for the other. For these reasons, this article considers the epidemiology of ovarian and endometrial cancer together, with the goal of providing a more unified perspective. The author does not address the epidemiology of cervical cancer in this article, though this is not for lack of importance. Worldwide cervical cancer is a greater source of morbidity and mortality than endometrial and ovarian cancer combined ( Table 1 ). However, there are far fewer epidemiologic uncertainties related to cervical cancer, and the means of its prevention and early detection are in hand, if not yet fully implemented where they are most needed.
| Region | Incidence | Mortality | ||||
|---|---|---|---|---|---|---|
| Cervix | Endometrium | Ovary | Cervix | Endometrium | Ovary | |
| World | 15.3 | 8.2 | 6.3 | 7.8 | 2.0 | 3.8 |
| More developed regions | 9.1 | 13.0 | 9.3 | 3.1 | 2.3 | 5.1 |
| Less developed regions | 17.8 | 5.9 | 5.0 | 9.8 | 1.7 | 3.1 |
| Eastern Africa | 34.5 | 2.4 | 4.0 | 25.3 | 0.8 | 3.3 |
| Middle Africa | 23.0 | 1.9 | 4.3 | 17.0 | 0.7 | 3.6 |
| Northern Africa | 6.6 | 2.2 | 4.8 | 4.0 | 0.7 | 3.7 |
| Southern Africa | 26.8 | 6.9 | 3.8 | 14.8 | 2.1 | 2.8 |
| Western Africa | 33.7 | 1.9 | 3.8 | 24.0 | 0.7 | 3.1 |
| Caribbean | 20.8 | 9.0 | 4.3 | 9.4 | 3.3 | 2.7 |
| Central America | 22.2 | 6.1 | 5.2 | 11.1 | 2.5 | 3.4 |
| South America | 24.1 | 4.4 | 6.2 | 10.8 | 1.7 | 3.4 |
| Northern America | 5.7 | 16.4 | 8.7 | 1.7 | 2.4 | 5.4 |
| Eastern Asia | 9.6 | 10.3 | 4.3 | 3.9 | 2.2 | 1.8 |
| South-Eastern Asia | 15.8 | 5.7 | 6.6 | 8.3 | 2.0 | 4.4 |
| South-Central Asia | 24.6 | 2.1 | 5.5 | 14.1 | 1.1 | 4.1 |
| Western Asia | 4.5 | 5.6 | 4.8 | 2.1 | 1.5 | 3.6 |
| Central and Eastern Europe | 14.7 | 14.6 | 11.0 | 6.2 | 3.4 | 5.9 |
| Northern Europe | 8.4 | 13.8 | 11.8 | 2.5 | 2.2 | 6.5 |
| Southern Europe | 8.1 | 10.4 | 8.4 | 2.5 | 1.9 | 4.2 |
| Western Europe | 6.9 | 11.2 | 8.9 | 2.0 | 1.8 | 4.9 |
| Oceania | 8.0 | 10.8 | 7.6 | 3.6 | 1.7 | 4.7 |
| Australia/New Zealand | 5.0 | 11.5 | 7.8 | 1.4 | 1.6 | 4.6 |
| Melanesia | 23.7 | 5.2 | 5.1 | 16.6 | 2.0 | 4.2 |
| Micronesia | 9.5 | 8.0 | 6.1 | 3.4 | 5.3 | 5.2 |
| Polynesia | 16.7 | 11.5 | 5.0 | 6.0 | 2.6 | 3.8 |
a Age-adjusted incidence rates are per 100,000 and are adjusted to the World Standard.
Tumor heterogeneity as it may affect epidemiologic associations
Before discussing the epidemiology of endometrial and ovarian cancer, it must be pointed out that neither of these cancers is homogeneous from a histopathologic standpoint. Cancer registries often include endometrial cancer under the broader category “cancers of the uterine corpus,” which includes sarcomas that arise from the endometrial stroma or from the smooth muscle of the uterus. Adenocarcinomas comprise the vast majority of cancers of the uterine corpus, and most epidemiologic studies are restricted to these. In turn, endometrial adenocarcinomas may be further subdivided, with endometrioid (or Type I) cancers accounting for majority, about 85%, and the remainder designated Type II and including adenosquamous, serous papillary, clear cell, and undifferentiated types, similar to those found in the ovary.
There is an even greater degree of heterogeneity for ovarian cancer. Ovarian malignancies may arise from germ cell, stromal, or epithelial compartments. Counting benign neoplasms, about 25% of all ovarian tumors are of germ cell origin. Most common is the mature teratoma (dermoid), which accounts for nearly one-third of all benign ovarian neoplasms, but only 2% to 3% of germ cell tumors are malignant. Ovarian stromal tumors account for 6% of all benign and malignant ovarian tumors with the most common being the granulosa cell tumor, which accounts for approximately 10% of malignant ovarian cancers. The most common types of malignant ovarian cancers are epithelial and parallel the same types arising in the endometrium. Four major histologic subtypes of epithelial ovarian cancer have been described, each resembling different types of epithelia found in the female reproductive tract. Features associated with fallopian tube, endocervical epithelium, or endometrial epithelium are observed in serous, mucinous, and endometrioid forms of ovarian cancer, respectively. Clear cell tumors are the fourth major histologic subtype and are identified by clear, peglike cells that resemble the lining of the endometrial glands during pregnancy. The majority of malignant ovarian tumors fall into the invasive serous category followed by endometrioid, clear cell, and mucinous types.
A distinction made for ovarian cancer that does not have an exact parallel in endometrial cancer is the designation of borderline or low malignant potential (LMP) ovarian tumor types that may spread beyond the ovary, yet generally have an indolent course and account for about 17% to 18% of ovarian cancers. The Surveillance, Epidemiology, and End Result (SEER) agency at the National Cancer Institute decided to no longer count LMP ovarian tumors as cancers after January 1, 2004. As a consequence, about a 20% “decrease” in the incidence of ovarian cancer and a 5% decrease in mortality occurred between 2004 and 2006.
In conclusion, then, epidemiologic patterns observed for endometrial cancer are most likely to pertain to the Type I cancers whereas those for ovarian cancer tend toward invasive serous. However, because of the greater heterogeneity of ovarian cancer, the mix of cases from study to study may influence epidemiologic associations reported for ovarian cancer, especially if LMP tumors are included.
Age and geographic distribution
In the United States endometrial cancer is the most common gynecologic cancer, accounting for 40,100 new cases and 7470 deaths. Ovarian cancer accounts for fewer cases (21,650) but more deaths (15,520). Ovarian cancer is the leading cause of death from a gynecologic cancer and the fifth leading cause of cancer deaths overall in the United States. Endometrial and ovarian cancer share similar patterns of distribution by age and geography. The incidence of both cancers increases sharply during the perimenopausal years and reaches a peak well after the menopause ( Fig. 1 ). Endometrial cancer rates drop after age 70 years, but ovarian cancer rates continue to increase into a woman’s eighties. It should be appreciated that the age-specific rates for ovarian cancer calculated by SEER are based on the entire United States population of females, including those who have had hysterectomy or hysterectomy and oophorectomy. Except when the surgery was done for endometrial or ovarian cancer, women who have had such operations are virtually at no future risk for these cancers. For this reason it is estimated that rates overall are about 33% higher for endometrial cancer and about 15% higher for ovarian cancer, although the exact percentages differ somewhat by age. The corresponding dashed lines in Fig. 1 illustrate the predicted higher incidence rates for women who still have their uterus or ovaries. Using these corrected incidence rates, the lifetime risk for endometrial cancer is about 5.7% if women with hysterectomy for benign conditions are excluded and about 2.5% for ovarian cancer if women with hysterectomy and oophorectomy are excluded.
Worldwide, higher rates of endometrial and ovarian cancer are observed in industrialized and northern European populations, and lower rates in Third World countries ( Table 1 ). There is a positive correlation between the occurrence of endometrial cancer and ovarian cancer that is significant (Pearson correlation = 0.76, P <.001). For comparison, the rates of cervical cancer are also shown, and are inversely correlated with both endometrial cancer (Pearson correlation = −0.64, P <.001) and ovarian cancer (Pearson correlation = −0.57, P = .003).
Age and geographic distribution
In the United States endometrial cancer is the most common gynecologic cancer, accounting for 40,100 new cases and 7470 deaths. Ovarian cancer accounts for fewer cases (21,650) but more deaths (15,520). Ovarian cancer is the leading cause of death from a gynecologic cancer and the fifth leading cause of cancer deaths overall in the United States. Endometrial and ovarian cancer share similar patterns of distribution by age and geography. The incidence of both cancers increases sharply during the perimenopausal years and reaches a peak well after the menopause ( Fig. 1 ). Endometrial cancer rates drop after age 70 years, but ovarian cancer rates continue to increase into a woman’s eighties. It should be appreciated that the age-specific rates for ovarian cancer calculated by SEER are based on the entire United States population of females, including those who have had hysterectomy or hysterectomy and oophorectomy. Except when the surgery was done for endometrial or ovarian cancer, women who have had such operations are virtually at no future risk for these cancers. For this reason it is estimated that rates overall are about 33% higher for endometrial cancer and about 15% higher for ovarian cancer, although the exact percentages differ somewhat by age. The corresponding dashed lines in Fig. 1 illustrate the predicted higher incidence rates for women who still have their uterus or ovaries. Using these corrected incidence rates, the lifetime risk for endometrial cancer is about 5.7% if women with hysterectomy for benign conditions are excluded and about 2.5% for ovarian cancer if women with hysterectomy and oophorectomy are excluded.
Worldwide, higher rates of endometrial and ovarian cancer are observed in industrialized and northern European populations, and lower rates in Third World countries ( Table 1 ). There is a positive correlation between the occurrence of endometrial cancer and ovarian cancer that is significant (Pearson correlation = 0.76, P <.001). For comparison, the rates of cervical cancer are also shown, and are inversely correlated with both endometrial cancer (Pearson correlation = −0.64, P <.001) and ovarian cancer (Pearson correlation = −0.57, P = .003).
Risk factors
This section considers personal risk factors for endometrial and ovarian cancers organized under the following headings: menstrual and reproductive events, medical history, and habits and environment ( Table 2 ). Genetic risk for these cancers is treated in a separate article by Karen Lu elsewhere in this issue.
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