-: Hi, all,
and welcome to today's lecture
on the "Epidemiology of Uterine Cancer".
In this lecture, we have several goals.
We're going to review the anatomy
of the corpus uteri
to discuss the global burden of corpus uterine cancer,
contrast trends in endometrial and cervical cancer,
discuss risk factors for endometrial cancer,
and discuss preventive factors for endometrial cancer.
We'll conclude by looking
at prevention and control strategies.
So, first, looking at incidence rates
of cancer of the corpus uteri, or uterine cancer,
cancer was diagnosed in 319,605 women
and caused 76,155 deaths in 2012.
Annual incidence rates are highest in developed countries
of North America, Russia, Europe, and Scandinavia.
All of those places have rates
higher than 15 cases per 100,000,
and lowest in underdeveloped countries
of Southeast Asia and Africa,
which all have cases numbering less than three
per 100,000 per year.
Due to shared risk factors at heighten exposure
to both endogenous and exogenous estrogens,
the global pattern of corpus uteri cancer
is similar to that of breast cancer.
The trends of mortality generally follow the trends
and incidence for corpus uterine cancer as well.
So, we see that the global burden of cancer
of the corpus uteri has increased sharply
in the 21st century unfortunately.
And, during the time span from 2012,
reported numbers of new cases and deaths have increased
by 69% and 70% respectively.
When we look at uterine cancer in 2020,
we see that there's age...
An age-standardized incidence rate
of 8.7 per 100,000 women globally,
and an age-standardized mortality
of 1.8 per 100,000 women globally.
So, next, let's turn to the anatomy of the...
Of the uterine corpus.
So, we'll note that endometrial carcinomas
account for 92% of malignant tumors of the corpus uteri.
These tumors arise from the epithelial lining
of the endometrium as we see here.
Histologically, endometrial carcinomas
are adenocarcinomas that show glandular characteristics
under the microscope.
In addition to the endometrial carcinomas,
sarcomas derived from connective tissues of the uterus
account for only 3% of uterine cancers.
There are two subtypes of corpus uterine cancer,
carcinosarcomas and mixed malignant malarian tumors.
Those account for the final 5% of uterine cancers.
These tumors consist of a mix
of glandular and connective tissues.
Finally, the very rare final type of cancer
of the corpus uteri is choriocarcinoma,
and that's a rare type of uterine malignancy
that occasionally develops during pregnancy.
So, endometrial cancer accounts
for about 10% of female cancers,
and 80 to 90% of cases are diagnosed after menopause.
There's the peak incidence at 55 to 65 years
of 60 per 100,000,
and 40,320 new endometrial cancers were...
Are diagnosed in the US annually.
There's also a little over 7,000 deaths
from endometrial cancer in the US annually.
In high income countries,
endometrial cancer has surpassed cervical cancer
as the leading gynecological malignancy in women.
Annual incidence rates of endometrial cancer
among American women
have trended upwards since 2000,
and are now three to four times higher
than cervical cancer rates,
which continue to decline.
Recent increases in the incidence of endometrial cancer
and declining rates of cervical cancer
are also evident in Great Britain, Western Europe,
Scandinavia, and Australia.
So, when we look at endometrial cancer risk factors,
we see some similarities
to those of cervical cancer and breast cancer.
So, namely, we see the early menarche, late first pregnancy,
and late menopause are all play a role
in the development of endometrial cancer.
Others, factors include infertility,
obesity and hypertension, familial history,
cancer family syndrome, diabetes,
estrogen replacement therapy,
and selective estrogen receptor modulation.
So, as mentioned previously,
the majority of endometrial cancer cases
or plurality of endometrial cancer cases
are diagnosed between 55 to 64 years of age.
It's also important to note
that there are type one and type two cancers
when we discuss endometrial cancer.
These are differentiated according to the dependence
or lack of dependence on estrogen
for growth and development.
Essentially, type one cancers,
which make up a 90% of endometrial cancers
are estrogen dependent
and contain estrogen receptor...
Estrogen receptors or they're ER positive.
On the other hand, type two cancers,
which are 10% of endometrial cancers,
are non estrogen dependent,
and are ER negative.
So, here we'll look a little bit more
at the pathology and carcinogenesis of endometrial cancer
by looking at the endometrial or menstrual cycle.
So, we see,
as we've discussed in the breast
and cervical cancer lectures,
a sustained exposure to estrogen,
particularly in the absence of progesterone
or unopposed estrogen,
may increase the mitotic rate
and cause atypical hyperplasia of the mammary epithelium
or endometrial epithelium,
which increases the chance of cancer development.
That is when there are high levels of estrogen
and low levels of progesterone,
cells are dividing more frequently,
leading to possibly a higher risk of cancer.
The chronic repetitive inflammatory process of menstruation
may also play an important role
in the genesis of endometrial cancer.
As we've discussed before,
inflammation is closely tied to cancer development.
As we've discussed before as well,
polycystic ovary syndrome,
where in women of reproductive age
develop bilateral ovarian cysts
in association with prolonged anovulation, infertility,
excess ovarian secretion of androgens,
and endometriosis may be related to endometrial cancer.
And, in fact, results of some studies have shown
that women with this syndrome have a fourfold increase
in risk of endometrial cancer as opposed to healthy women.
One mechanism underlying this association
is during an anovulatory menstrual cycle,
there's increased exposure of the endometrium to estrogens,
unopposed by progesterone.
Granulosis cell ovarian tumors
occasionally develop an association with menstrual cell...
Menstrual cycle irregularities, infertility,
and vaginal bleeding.
Human ovarian granulosis cells secret excess estrogen,
which in turn stimulates estrogen receptors
and other tissues
and in the endometry...
In the endometrium.
And, due to hyperestrogenism and hormonal imbalance,
endometrial cancers develop in about 10% of women
with ovarian granulosis cell tumors.
Finally, endometriosis or the abnormal presence
of endometrial glands
in the myometrium or muscle tissues,
ovaries, uterine ligaments, vagina, et cetera,
can lead to significant symptoms,
including bleeding, inflammation, cystic formation,
and fibrosis.
And, this can be diagnosed with colonoscopy or pathology,
and it increases the risk of ovarian cancer,
but has not been linked to endometrial cancer.
Obesity is a significant risk factor of endometrial cancer
due to higher endogenous estrogen levels
in obese individuals
and reduced levels of sex hormone, blighting,
binding globulins, or a type of protein.
Diabetes also plays a role
in the development of endometrial cancer.
And, for type two diabetics,
there's a twofold risk increase
in the development of endometrial cancer.
There's a threefold risk increase for type one diabetics.
Next, we see that in the early 1970s,
the incidence of endometrial cancer abruptly doubled
among many Caucasian women in the US.
This phenomenon was observed shortly
after a marked increase in estrogen replacement therapy
or equine estrogens,
for the treatment of hot flashes at the time of menopause
in some American women.
Subsequent epidemiologic studies
consistently revealed significant increases
in the risk of developing endometrial cancer among women
who received estrogen replacement therapy.
And, this risk persisted for more than 10 years
after discontinuation of use of hormone replacement therapy.
However, again, I'll point out that it's important
to view the New York Times Magazine article
in the American Dissected Podcast,
which discusses some recent revelations
about the use of hormone replacement therapy
in relation to the development of cancer,
including some ways in which the data of that study
may have been interpreted
in less than completely accurate fashion.
The decline in the incidence of endometrial cancer
to pre-1970 levels during the 1980s
is ascribed to the introduction of progesterones
as part of the hormonal replacement regimen.
So, there's several key steps that can be taken
to reduce one's risk of endometrial cancer.
These include oral contraceptive use, regular exercise,
the use of aspirin, consuming coffee...
Or, consuming coffee,
lowering one's rate of chronic smoking,
and undergoing hysterectomy.
So, the use of oral contraceptives
has been sure to decrease the risk
of developing endometrial cancer.
In a meta-analysis of 11 studies,
duration of use was found to be inversely related to risk.
That is, the longer one uses contraceptives,
the greater they decrease their risk of...
Or, of developing ovarian or endometrial cancer rather.
Compared to women with no exposure,
12 years of using oral contraceptive
reduced the risk by 72%,
and this effect persisted
for 20 years after discontinuation.
When we look at the genetics of endometrial cancer
to discuss familial inheritance briefly,
we see that type one tumors,
or the estrogen dependent ones,
are related to PTEN mutations and Cowden's Disease.
We also see the type two tumors
are those that are estrogen independent,
are related to familial passage of P53 mutations
and Lynch Syndromes.
Next, we see that there are other key tumors of this system,
though they are much rarer than endometrial tumors.
So, leiomyomas, or fibroid tumors,
are benign tumors with smooth muscle
occurring in 25% of women during reproductive years.
So, these tumors are benign,
and they cause discomfort and bleeding,
and are similar to endometrial cancer
in regard to their risk factors.
They're oftentimes treated with surgery.
Leiomyosarcoma is a rare malignancy
that arises from smooth muscle, or the myometrium,
or connective tissues of the uterus.
The...
Whether they're derived from preexisting benign leiomyomas
remains a highly controversial issue.
Choriocarcinomas are rare tumors
that develop from trophoblastic cells
that ordinarily form the chorionic membranes
of the placenta.
These are malignancies that occur during pregnancy.
The majority of these choriocarcinomas
develop in the endometrium,
though they can also rise in extra uterine sites,
like the ovaries or fallopian tubes
in association with ectopic pregnancy.
Approximately 50% of choriocarcinomas
develop from hydatidiform moles
and 20% are in association
with spontaneous abortions and miscarriages,
20 to 30% in normal pregnancies,
and two to 3% in ectopic pregnancies.
Since these tissues with choriocarcinomas
secrete human chorionic gonadotropin, or HCG,
a marked elevation in the blood tissue of this hormone
serves as an early biomarker of tumor development
and a good tool to be leveraged when screening
for choriocarcinomas.
Again, I'll note that these,
these tissues and compounds
that are not listed on the slide
are in the slide notes below,
so I'd encourage you to check those out if you haven't yet.