00:01
Pathogenesis of cervical cancer.
00:04
I'll quickly walk you through the
algorithm that's important for you.
00:08
You’ve seen this before in
some way, shape, or form.
00:11
I like the organization pattern that
is being established here for you.
00:15
Sexual activity.
00:17
The more that you have a
partner that is promiscuous,
then she increases her
risk for HPV exposure.
00:26
In basic pathology, we
talked about neoplasia.
00:29
In neoplasia, we talked about
HPV high-risk strain containing
particular oncogenes.
00:35
And those included E6 and E7.
00:38
E6 knocked out p53;
E7 knocked out Rb.
00:44
If you knock out the
tumor suppressor gene,
you are now going to choose a
cell in the transformation zone
of either becoming an
adenocarcinoma or a squamous.
00:55
Your focus will be on the left
branch of this algorithm.
01:00
Infection with high-risk HPV is very common,
and is seen in up to 80% of sexually active adults before age 50.
01:06
It is transient and clears on its own in majority of the cases.
01:10
Only a few women who have persistent infection
may finally develop cervical intraepithelial neoplasia (CIN) or cervical cancer in later years.
01:18
The risk of progression in the high-risk HPV-positive women with a normal cervix
or low-grade lesion on colposcopy and histopathology at baseline is not yet clear,
but about 10% of women with HPV infection will develop a persistent viral infection that puts them at risk for cervical cancer.
01:35
It is important to know the most common high-risk strains of HPV are 16 and 18.
01:40
Similarly, when high-risk HPV lingers and infects the cells of the vulva, vagina, penis, or anus, it can cause dysplasia.
01:49
So now, you begin the
process of dysplasia,
and there are three
different types.
01:57
CIN 1, CIN 2, CIN 3.
02:00
Cervical intraepithelial
neoplasia, CIN 1, 2, 3.
02:07
You go straight to CIN 3.
02:09
Close your eyes.
02:10
What’s happening right now? Dysplasia.
02:12
Dysplasia.
02:13
Can you picture increased
proliferation of
squamous cells right now?
That means that the
membrane is getting more --
it’s bearing more
and more weight.
02:23
Think of it that way.
02:25
With all this proliferation,
the membrane, which
is still intact,
is now bearing all this weight.
02:31
Oh my goodness.
02:33
At some point, from CIN 3, you’re
going to become malignant.
02:38
At this point, what
form are you in?
You’re in dysplasia.
02:42
That is not a neoplasia.
02:44
It is a dysplasia, but
it’s not a cancer.
02:47
It’s not malignant.
02:49
So your next step in terms of
malignancy will be in situ.
02:51
And then you’re going to invade.
02:54
If you then invade, you become
now invasive cervical cancer.
02:58
Let’s pause here for a second.
03:01
You should be familiar
with CIN 1, 2, and 3.
03:03
We’ve talked about
it in microbiology.
03:04
I will talk to you about
this a little bit more.
03:06
However, clinically,
this might be new
information for you,
that you need to make sure
that you’re familiar with.
03:15
You no longer will call this
CIN when you document it.
03:19
When you document the changes
that you find on Pap smear,
okay, you’ve taken a
sample of the cell
and you’re looking at it now.
03:27
When you document it,
you’ll be writing down
what type of SIL has
been taking place.
03:36
SIL stands for squamous
intraepithelial lesion, SIL.
03:41
There is either low
grade or high grade.
03:44
Please focus upon
high grade SIL.
03:48
What high grade SIL means
is the fact that you’re
getting step by step by step
closer to invasive squamous cancer.
03:58
Here we have the
following, high grade and
also risk factors that are involved.
04:03
Smoking, oral contraceptive
pills, high parity,
altered immune status, and maybe
perhaps, host gene alterations
All of these
factors, high grade,
you’re increasing risk of?
Invasive squamous cancer.
04:21
Take a look at the very left.
We have low grade.
04:24
Low grade has a rare chance of going
on to invasive squamous cancer.
04:29
Think of this, please,
as being like CIN 1.
04:34
Once you go past CIN 1
and you go into CIN 2 and 3,
this is your high grade.
04:43
And once again, to high grade,
you’ll increase the
chance of going on to?
Invasive squamous cancer
of what organ right now?
Cervical.
04:52
How important is this?
Worldwide developing countries,
cervical invasive cancer is the
number one cancer gynecologically.
05:03
What about the other side?
On the right branch,
what part of the cervix are
we in if it’s columnar?
Endocervical columnar
differentiation.
05:14
If this is endocervical, what
kind of cells are these?
Good.
05:19
These are columnar cells.
05:21
Therefore, why would you ever call
this squamous intraepithelial lesion?
That makes no sense.
05:28
You would call this glandular
intraepithelial lesion.
05:32
"But Dr. Raj, I’ve never
heard of that before."
That’s okay, that’s good,
because that means that
you’ve been taught
that majority of your cervical
cancer is of what type?
Squamous, squamous,
squamous.
05:44
Human papillomavirus (HPV) is central to the development of cervical neoplasia
and can be detected in 99.7 percent of cervical cancers.
05:53
HPV types 16 and 18 are found in over 70 percent of all cervical cancers, with other high-risk subtypes seen less often.
06:01
The most common histologic types of cervical cancer are squamous cell
(70 to 75 percent of the time) and adenocarcinoma (about 25 percent of the time).
06:11
Other rare types are adenosquamous, adenoid cystic, neuroendocrine, mixed, and undifferentiated carcinomas.
06:19
Most abnormalities are treated early with detection on Pap smears
and never progress to cervical cancer when patients have regular screening.