Cancer De Cervix

ok moving along the next section is thecervix remember that the cervix is the neck hence the term cervix of the uterusand it's divided into the access service in the end of cervix now the idea hereis that when you do a clinical exam you can actually visualize the excess cervixand sometimes you can visualize the end of cervix what's importanthistologically is that when you look at the exxon endo cervix is a very distinctdemarcation between them and there are different types of epithelium that coverthem for example of this is the basement membrane and we're trying the excesscervix and the end of cervix 10 remember that the excess cervix say that's here

exo cervix is lined by squamousepithelium like that and so this would be the excess cervix and then the end ofcervix is lionized by colombian are epithelium and the distinction betweenthe xo and the end of service so sharp that is actually a single cell that youcan actually sort of make that distinction between it's very very clearon histology and that lends to a very clear demarcation clinically as wellhere's a picture just highlighting that and just want to show you how sharp thisdemarcation is this is the squamous epithelium here and you can see this tobasket weaving of keratin that's occurring as we get to the top of thecell to the top of the epithelium and

this is the end the excess service hereand then you can clearly see that here you've got all these individualkilometer so and so this represents the end of cervix now important to note thatthis region here that i'm driving the arrow towards where you make a markasian occurs that's called the transformation zone and the whole storyof what we're going to discuss in the cervix it is that story of what happensat the transformation zone the only real pathology that we're going to discuss inthis section of the highest yield and really the most important clinically aswell as hpv infection now remember in our discussion of the volvo that i toldyou a lot about hpv hpv is characterized

by quality change page bibi is a dnavirus you can subtype that dna virus using dna sequencing into high risk low risk low risk for example 6 and 11classically causes of condyloma high risk for example 1618 and then 3133 andsome others would result in dysplasia and then just place it would eventuallyresult in carcinoma and so that's the basics that you really have to have wellembedded in your mind concerning hpb and that's what i basically stated here it'sa sexually-transmitted dna virus that infects the lower genital tract forexample if it infects the volvo you get condyloma or just pleasure if it impactsthem in the vaginal canal you can get

kinda long or displeasure and it affectsthe cervix you get condyloma or dysplasia in one of the most commonregions among the women the entire lower genital tract would be the cervixespecially the transformation zone and that's important the transformation zoneis the key place in the lower genital tract or hpv likes to in fact now what'sanother important interesting thing about hpv is that weekend and hpvinteraction of someone were to get an hiv infection the vast majority of hpv infection isactually cleared by the immune system probably about ninety percent of thetime when anyone gets an hpv infection

but that's just going to be cleared bythe immune system it's only when persistent infection occurs which isrelatively rare considering the number of infections out there when it with onepersistent infection occurs then a risk results for cin and so again you needpersistent infection now i've already mentioned and i'm just going to repeathere that the risk of cin with persistent infection depends on the typeof hpv so for example i risks are underlined here and low-risk surrenderand underlined here and have already discussed this and it's already writtenin your book is well what is fairly high yield and i cannot emphasize this enoughand students need to be able to take

this discussion one step further to thispoint is and that is what makes high risk hpv high risk what is it about thevirus that actually makes it i rose and the answer is a high-risk hpv is itproduced two proteins g6 and east and west to east 67 do they knock out p53and retinoblastoma respectively so when you have these six beingproduced by the hpv virus the high risk hpv virus they are then results in the destructionof p53 and you're well aware of the fact that p53 is an important tumorsuppressor gene remember that p53 its job is to regulate the g1 to s phase ofthe cell cycle and it basically looks at

the amount of dna damage that's presentin the cell and make sure that the dna damage is repaired before the sale goesto s phase when we remember that there's too much dna damage p53 has the abilityto induce apoptosis so basically p53 looks at the sounds has put your handsup let me check your dna dna as damaging blows a molecular whistle and calls inrepair enzymes to repair enzymes and fix our dna and the cells allowed to go asphase if there's too much damn p53 blows a molecular whistle calls in a moleculecalled you remember the name back backtracked out another molecule whichis bc all to remember that bc 02 is the molecule that stabilizes themitochondrial membrane so that loss of

stability of the mitochondrial membraneallows cytochrome c to leak out at a crime scene activates apoptosis and thenkills itself so that's the way by which p53 regulates that g1 to s phase and ofcourse if you destroy 353 there's going to be no regulation to remove dnamutations or cells that are you cheated out with their ourselves in which thedna is actually mutated and so therefore p53 loss of p53 would have a majoreffect and carcinogenesis and that's why high risk hpv can result in disclosureand then cancer and he seven what it does is it knocks out retinoblastoma andyou recall the retinoblastoma holds a very important molecule which is calledeach to each other's necessary

preparation to this cycle you must passfor 11 oberstar before it will release its you out if you destroyretinoblastoma each about this floating around free and therefore will be ableto be taken up by the cell and moved or used by the cell to move into the g1 sphase so you need these two essential tumor suppressor genes and the high-riskhpv is a knockout both of these key genes this is a very high yielddiscussion for examinations i cannot emphasize enough shows up all the time right now forpatient were to get persistent high risk hpv the risk will be development of cinand basically cin is displeasure bad

growth so that you get atypical cellswith high-end see ratio increased mitotic activity in nuclear atypia andclothes change because there's an hpv infection and these cells begin to pileup in the epithelium of the cervix and based on the extent of these dysplasticcells we can divide cin into multiple so let's do that here this is the cervix oklet's pretend that the cervix is made up of 123456789 cells just as an example iftheir displeasure involves any one of these first three cells that would bethe first one third we would call at cin 1 if the displeasure progresses andextends beyond their to involve any any any cells within these this middletwo-thirds to now you know the first six

cells in that letter for example we callthat cia into if the display text ends up to involve most of that epithelialnumber call that cin 3 if the dysplasia involves the entirethickness of the epithelium we call that carcinoma in situ ok important question what's thedistinction between dysplasia and carcinoma why do we make thatdistinction can you remember from the neoplasia lectures what's the keyfeature that distinguishes displeasure from carcinoma the answer isreversibility cin juan has the potential to reverse cin 2 as a potential toreporters and cin three very very rarely

could potentially reverse but once youhave carcinoma in situ there is no reversibility and carcinoma in situ thenext step will be invasion producing a squamous cell carcinoma and indecent nowremember that cin 1 it reverses about 66 percent of the time and cnn to reverseis about 33 percent of the time but see i m three is very unlikely to reversethe more you progress and cin the less likely you are to reverse backto something less than the level at which you're at so that's an importantunderstanding that should be in our minds concerning cin and that is that wecan divide that is that we can club classify the extent of dysplasia nowhere's a classic picture of cin and let

me take you back a couple pictures andshow you the normal for a minute so here is a normal and i'm gonna raise that tojust show you that this is what the normal squamous epithelium looks likenotice that the cells become as you going towards the top they become smaller and their nucleusbecome smaller look at how look how tiny that no classes for example compared tothe nucleus there now for go back and look at the picture that i just showedyou look at these cells are not becoming pink they're really dark blue whateveris at the bottom looks exactly like what's at the top so from top to bottomhere we've got dysplastic cells now

basically our look here i would say thatthis is carcinoma in situ at this point here maybe if i were to look here and isee a little bit of painting of the cells and a little bit of maturation imight call that area's 30 just just to highlight this discussion but the pointis when you look at an area like this you've got these large blue cells fromtop to bottom you're really going to call thiscarcinoma in situ so that's what i want to highlight from this image present inyour text now again you know that cin progressive step away so there you gofrom one to two then 2233 to cis and eventually too invasive carcinoma butit's not inevitable as i told you it may

regress in particular cin 1 regressive66 percent of the time cnt regreses about 33 percent of thetime and cin 3 as much as very unlikely to regress but it's very likely toprogress to carcinoma in situ no corresponding ones patients getcarcinoma in situ and eventually develop invasive carcinoma and then we call thatcervical carcinoma now the invasive carcinoma the key feature is that itgoes through the basement membrane that's what distinguishes carcinoma insitu from invasive carcinoma in the invasive carcinoma usually arises inthese patients in a middle aged woman and the idea here is that the hpvinfection will occur early in the

woman's life like the age of or 25 and it takes about 25 to 30 yearsbefore the patient actually developed a full blown carcinoma and that's becauseit takes time to go through this displeasure carcinoma sequence theclassic presentation will be vaginal bleeding the woman would present witheither bleeding from vaginal canal or post coital bleeding bleeding afterintercourse those are two classic presentations for cervical carcinomawhat's the key risk factor for cervical carcinoma we've already discussed itit's high risk hpv infection now everybody knows you need to know againthat the high risk viruses are 16 and 18

and then 31 and 33 rd are also commonthread there are other ones they are a little less common you need to know thatthe high-risk hpv produces g6 and g7 g6 next up 353 east unnaturalretinoblastoma so that's what i would say concerning the key risk factors now there are some secondary riskfactors that will also increase the risk and there's two that you really shouldbe aware of the first two smoking now it's important to remember smoking heregenerally speaking when i think about smoking i think about the things thatmakes sense for example obviously smoking is going to increase the risk oforopharyngeal carcinoma because the

smoke it see our offerings obviouslysmoking would increase the risk of esophageal squamous cell carcinomabecause the smoke hits the esophagus some of it goes down the throat when thepatient's breathing in for example obviously smoking would increase therisk of lung cancer because it goes to the long it makes sense of smoking wouldincrease the risk of kidney cancer and euro and you're a feeling of carcinomabecause the kidney takes all of those carcinogens and go into the blood and itconcentrated in the urine so anything that the year is going to touch is goingto have an increased risk of cancer when a patient smokes so those are make sensebut there's two that you can have to

remember beyond does that make sense one is cervix and the other is pancreasso won an important risk factor for cervical carcinoma smoking an importantrisk factor for pancreatic carcinoma is smoking so that's what i would like tosee about smoking immunodeficiency is very high yieldwhite because remember that it's the vast majority of the time we actuallyuse our immune system to destroy the virus and so the immune system is easy essential in this disease to remove thethe essential car initiator of the disease to begin with and so patientswho are immune deficient they have an

increased risk of developing cervicalcarcinoma and interesting if you were to go and take a list of the aids definingillnesses remember that there are a series of illnesses that you can use tocall a patient who has hiv as now having aids and those are called those arecalled the aids defining illnesses one of them on that list is is cervicalcarcinoma patients actually developed a cervical carcinoma with hiv that's apotential aids defining illness and this is a very high you point to to to beaware of ok now remember that when patients getcervical carcinoma they can actually get to type so we've got the excess servicein the end of service and you've got

squamous cells and the excess cervix andthen you got calumny ourselves in the end of cervix so that patients candevelop squamous cell carcinoma and they can also develop an adenocarcinoma andsquamous is much more common area known as little bit less rare is a little bitless common but what i really want you to remember is that both are associatedwith hpv gonna sell carcinoma is driven by hpvbut patients who get adenocarcinoma it is also driven by hpv and examiners liketo ask you which of the following is doing hpv and adenocarcinoma etc rightnow you need to know that adenocarcinoma the cervix is also givenby hpv another very important principle

conserving cervical cancer is that thetumor tends to grow locally and doesn't metastasize until very very late and sothe classic findings are when when you have an advanced tumor one of theclassic findings is hydronephrosis now the idea here is that the tumor sort ofboris to the anterior and your uterine wall into the bladder and when he getsinto the bladder blocks to your orders and is the blocking of the arteries thatresults then in hydronephrosis with the eventual post renal failure and the mostcommon cause i should say one of the most common causes of death in patientswith cervical cancer is post renal failure and had with hydronephrosis

so we should be well aware of the factthat school cancers of the cervix one of the important characteristics of thesecancers is that they tend to locally create symptoms rather thanmetastasizing to a distant site and that's the mechanism by which patientscan expire with this cancer very high yield to be aware of remember that one of the ways by whichwe can avoid the whole issue of cervical cancer is screening and screening isessential the goal of screening in the context of cervix is to catch thatdysplasia before it becomes cancer remember they told you that patientsnormally get infected at about the age

of 25 are you know twenty and it takesabout 10 to 20 years in most cases twenty years before you actually developthat carcinoma and so we've got this twenty-year window or we can actuallycatch the patients with dysplasia and remove that disclosure before it becomescancer in the way by which we find that displayed is called the pap smear so thepap smear is the gold standard for screening and it is the most successfulcancer screening tests developed to date now the idea here is that you take abrush you go to the transformation zone and you scrape away the cells using thatbrush and then you put them on a slide and you look at the store sells underthe microscope you look under the

microscope we look for dysplasia andwhen we see displeasure we see characteristic features of malignantcells for example we see sales went dark nuclei and high and see ratios and thisis one of the key screening test for cervical cancer alright so here's a picture of cytologyand this is a picture of a pap smear basically this is a normal squamous celland these are the malignant cells and you can clearly see that compared thenuclear size this nucleus this tiny this nucleus is huge this cell has a very lowand see ratio with a lot of cytoplasm and a little bit of nucleus this cellhas a very high end see racial a lot of

nucleus a very little bit of cytoplasmnotice that the nucleus looks dark and hyper chromatic and so again these areall the features that we would expect to see and dysplasia and that's importantto bear in mind know when a patient has an abnormalpap smear remember that the pap smear is a screening test and every screeningtests in medicine must be confirmed and so the confirmatory tests called cop askippy where we basically put in a magnifying glass introduced a magnifyingglass into the cervical into the vaginal canal and you the cervix and when we dothe cervix we can apply asset to the cervix and we can then detect areas ofthat bill melody and biopsy those and so

when a patient has an abnormal pap smearthe next step will be biopsy and biopsy will then be sent to the pathologist inthe pathologist will then determine the extent of dysplastic cells there aresome limitations to the pap smear examiners like to go after thoselimitations first of all if a passenger is performedbut it's not done that the transformation zone in the screeningwould be inadequate you would not have actually tested the area that you wantedto test and so that would result in a false negative tests so that perhapsthat's one limitation of a pap smear another limitation of pap smear is thatit does not detect adenocarcinoma very

well now remember that we have adysplastic sequence where we had died in 1923 carcinoma in situ and invasivesquamous cell carcinoma but that applied to squamous lesions and adenocarcinomait's much more difficult to detect and it's not it doesn't go through that samesequence obviously and so there is a limited efficacy in screening foradenocarcinoma now what's interesting is that despite the pap smear all the greatthings that we have to say about the pap smear that all applies to squamous cellcarcinoma and despite the pap smear the incidence of adenocarcinoma has notdecreased significantly highlighting again the general principlethat the pap smear is good for squamous

cell carcinoma and its precursor lesionsbut is not good for adenocarcinoma for any carcinoma or its precursorlesions the last point and i wanna make concerns immunizations remember thatnumber one ministration is effective in preventing hpv infection that's thecurrent understanding the current immunization that we used to that seenas a quadrivalent vaccine it covers four subtypes important to know you got anotice for some types 6 and 11 they protect against the formation ofcondyloma and 16 and 18 protect against theformation of cia or dai han or vis great displeasure of the lower genital tractespecially cin no 16 and 18 high risk

subtypes and they are the most commonhigh-risk subjects involved in that dysplastic carcinoma sequence protectionlasts for about five years so you have to realize every five years and rememberthat the patient still must get pap smears why why did they still need toget pap smears the answer is because you're only protecting against 16 and 18what about 3133 and the other less common subtypes i could also result indysplasia so we have not eliminated by a vaccine the possibility of dysplasia thereforepatients still must undergo pap smear and that's a high yield principle to beaware of that close up our sectional

gonna move up the track next and go tomeet women myometrium