00:01
Welcome. In this talk we're going to cover
warts or verruca.
00:06
Very common lesions that almost all of us
have at least seen if we haven't personally
experienced. So these are benign.
00:15
I want to emphasize that they're totally
benign,
keratinocyte proliferations,
they're tumors,
but they almost never,
in fact, probably, I should say,
never convert into something that's
malignant.
00:26
But they're caused by human papillomavirus,
which is driving the proliferation of the
keratinocytes. And we'll talk a little bit
more about the pathophysiology momentarily.
00:36
So what's the epidemiology of verruca.
00:39
Well it's a fairly high incidence.
00:42
About 10% of the global population will have
it.
00:45
And probably after acne this is the second
most common cutaneous lesion that we'll see.
00:52
In terms of who gets it.
00:56
It's more common amongst immunosuppressed
individuals.
00:58
And that's probably because they are less
able to clear the virus that is driving this.
01:04
Interestingly enough,
meat handlers also have an increased
incidence, and that's probably because there
are papillomaviruses in the meat that they're
handling that is sufficiently able to enter
into the human host.
01:20
Plus, they're also having small areas of
trauma to their hands as they as they work
with knives in the meat.
01:27
There is no particular age predilection. You
can get it when you're a little tiny kid. You
can get it when you're a really old guy or
person.
01:33
Interestingly, lighter-skinned individuals
versus darker skinned individuals have a 2 to
1 incidence. Although the mechanisms and the
reasons behind that are not completely
understood, and there is a similar ratio of
women and men who are affected by this.
01:49
So let's talk a little bit about pathogenesis
since the story is pretty well known and it's
kind of cool, so bear with me.
01:56
There are well over 100 subtypes of the human
papillomavirus.
01:59
And this is going to be the agent that's
responsible for driving the proliferations
that get recognized as warts or verruca.
02:08
The subtypes, depending on their tropism,
will cause lesions at specific anatomic
sites. So you see here that subtype one,
two,
three, four, ten, 27,
57, etc.
02:18
cause cutaneous warts,
whereas six and 11 cause anogenital warts 16
and 18 have a tropism for the cervical or
vulvar vaginal epithelium.
02:30
You don't need to memorize those numbers,
although interestingly,
it will become important in the story of
cervical carcinoma,
which is going to be a different talk for a
different day and maybe even a different
speaker, because different subtypes of the
human papillomavirus infecting the cervical
epithelium have different propensities to
cause malignancy.
02:52
So that's a different kind of story.
02:54
But here we're mainly talking about the
subtypes that just cause benign
proliferations. Again you don't need to know
the numbers per se.
03:02
So what is going on here.
03:04
So we have a virus that is sitting at the
surface of the skin and provided we have
decent barrier function,
it can't get in to where it wants to go.
03:13
The cells can. The virus can usually only
enter basal cells,
so there has to be some break in the skin,
some trauma,
some micro injury that allows the virus to
get from the surface in the stratum corneum,
for example, down to the basal region,
which is the cell type that has to be
infected. The virus enters there,
and now it's not trying to drive
proliferation. That's not its goal in life.
03:42
It's just trying to make more virus.
03:43
Well, it turns out in order to make more
virus,
it needs to turn off the cellular machinery.
03:51
That would lead to further differentiation,
to the process of stopping mitosis and
starting maturation into mature
keratinocytes.
04:01
So it does so by a couple of different
mechanisms.
04:04
And in doing so by turning off that machinery
of the keratinocyte so you can make more
virus. It then causes proliferation of the
keratinocytes.
04:13
How is that happening?
So this is the cool stuff.
04:16
And you know I'm a nerd so bear with me.
04:19
This is important. And this same pathway by
the way is going on in cervical carcinoma.
04:24
So you kind of want to pay attention anyway.
04:27
The viral oncogenic proteins,
the ones that are going to drive the
proliferation of the keratinocytes do so
through two proteins.
04:34
One is called E6 and the other one is called
E7.
04:37
Terrible names. But whatever E stands for
early.
04:41
So they're early genes.
04:42
The E6 creates a protein that specifically
degrades p53.
04:48
And all of you know, p53 is the protector of
the genome.
04:54
It is the one that is going to be able to
drive apoptosis when a cell goes weird.
05:00
Okay. So we are turning off some of the
breaks that would normally limit
proliferation. The E7 protein,
the early seven protein degrades the
retinoblastoma protein.
05:13
Retinoblastoma is going to be a very
important break on the proliferative process.
05:17
It holds the elongation factor 2E2F in a
non-active form and keeps it from driving the
proliferation of cells.
05:26
The E6 broke down p53.
05:29
E7 broke down a retinoblastoma protein.
05:31
We've got two signals that say proliferate go
go go go.
05:36
So we get a basal epithelial cell
proliferation.
05:40
That then gives rise to a recognizable wart
to a benign tumor.
05:45
Now there are no other mutations going on
here.
05:49
So that's why these these tumors,
these proliferations don't turn bad.
05:54
They don't turn malignant.
05:56
So keep this in mind. There are other changes
that go on in cervical cancer.
06:01
But it's important to have this general
mechanism in mind because it is something
that does appear on boards.
06:08
So the transmission in fact it's direct skin
contact.
06:13
So the virus comes from one individual to the
next individual. But there's got to be a
break in the skin. Remember,
the virus has to get down to the basal layer.
06:21
Sexual activity for the transmission of the
virus that's responsible for anal genital
warts. Also, by virtue of the fact that the
sexual activity can cause minor breaks in the
skin. So there may be easier transmission in
that regard,
but it's kind of direct contact.
The lecture Warts (Verrucae): Definition and Pathophysiology by Richard Mitchell, MD, PhD is from the course Infection Conditions of the Skin.
What is required for human papillomavirus to successfully infect the skin?
Which protein does the viral E6 protein target to promote keratinocyte proliferation?
Which of the following populations has an increased incidence of cutaneous warts?
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