Cervical Cancer-1.pdf......................

Cervical cancer knowledge

1. Cervical Cancer (CaCx)
screening & cancer of
the cervix -overview
Dr. A. Kumwenda
MBChBlecture

2. TheWilsonandJungnerclassic
screeningcriteria(1)
Theconditionsoughtshouldbeanimportanthealth
problem.
Thereshouldbeanacceptedtreatmentforpatientswith
recognizeddisease.
Facilitiesfordiagnosisandtreatmentshouldbe
available.

3. TheWilsonandJungnerclassic
screeningcriteria(2)
Thereshouldbearecognizablelatentorearly
symptomaticstage.
Thereshouldbeasuitabletestorexamination.
Thetestshouldbeacceptabletothepopulation.
Thenaturalhistoryofthecondition,including
developmentfromlatenttodeclareddisease,shouldbe
adequatelyunderstood.

4. TheWilsonandJungnerclassic
screeningcriteria(3)
Thereshouldbeanagreedpolicyonwhomtotreatas
patients.
Thecostofcase-finding(includingdiagnosisand
treatmentofpatientsdiagnosed)shouldbe
economicallybalancedinrelationtopossible
expenditureonmedicalcareasawhole.
Case-findingshouldbeacontinuingprocessandnota
“onceandforall”project.

5. 5
Transformation zone (1)
Histology of transformation zone (TZ)
NearlyallcervicalneoplasiadevelopwithintheTZ
Endocervicalcanallinedbycolumnalepithelium
commonlyreferredtoas“glandular”
Ectocervixiscontinouswithvagina,coveredwith
squamouscellepithelium
Thetwomeetatthesquamocolumnarjunction(SCJ)

6. 6
Transformation zone (2)
Areaofhighactivity-duringpregnancyandpuberty
partialeversionoccurs,lowerpHcausesexposedarea
toundergometaplasia
Thismayexplainwhyearlyageatsexualactivityonsetand
atfirstpregnancyareriskfactorsforCaCx
TheTZisvulnerabletoagentsthatcausecancerandit
isfromthisregionthatcancerofcervixdevelops

7. Background (1)
CaCxisoneofthegravestthreatstowomen’slives.
AccordingtoWHO(2014),>amillion♀worldwide
currentlyhaveCaCx
Mostofthese♀havenotbeendiagnosed,nordothey
haveaccesstotreatmenttocurethemorprolongtheir
lives.
CaCxisthemostcommongynaecologiccancerin♀and
itkillsmore♀thananyotherformofcancerin55
countries

8. Background (2)
Mostearlycancersareasymptomatic
DiagnosisofCaCxusuallyfollowshistologicevaluation
ofbiopsiestaken
Thecancerisclinicallystaged
Treatmentvariesandistypicallydictatedbythe
staging

9. Burden of cervical cancer
In2012,528000newcasesofCaCxwerediagnosed,
and266000♀diedofthedisease
Almost9outofevery10oftheselivedanddiedinlowto
middleincomecountrieswhile1outofevery10ofthese
♀livedanddiedinhigh-incomecountries.
Zambiahas2
nd
highestratesintheworld,afterTanzania
Ratesare5timeshigherin♀withHIV

10. Top ten cancers seen at CDH -2014
28%
13%
6.4%
5% 4.5% 4%
2% 1.7%1.6%1.5%

11. Aetiology(1):
Primarycauseofcervicalpre-cancerandcanceris
persistentorchronicinfectionwithoneormoreofthe
“high-risk”(oroncogenic)typesofHPVin99.7%ofcases
HPVisthemostcommoninfectionacquiredduring
sexualrelations,usuallyearlyinsexuallife.
Inmost♀and♂whobecomeinfectedwithHPV,these
infectionswillresolvespontaneously.

12. Aetiology(2):
AminorityofHPVinfectionspersist
In♀thismayleadtocervicalpre-cancer,which,ifnot
treated,mayprogresstocancer10to20yearslater.
HIV+ve♀aremorelikelytodeveloppersistentHPV
infectionsatanearlierageandtodevelopcancer
sooner

13. Human Papillomavirus (HPV)
High-risk types
(oncogenic or cancer-
associated)
Low-risk types
(non-oncogenic)
16, 18, 31, 33, 35, 39, 45,
51, 52, 56, 58, 59, 68, 82
6, 11, 40, 42, 43, 44, 54, 61,
72, 73, 81
HPV types 16 and 18 cause 70% of cervical cancers
and 50% of high grade cervical precancer (CIN3)
Non-oncogenic subtypes, e.g. 6 and 11 cause low grade
cervical lesions and genital warts

14. Risk factors for cervical neoplasia (1)
Demographicriskfactors
Ethnicity
Lowsocioeconomicstatus
Increasingage
Behavioralriskfactors(some↑riskofacquiring
oncogenicHPVinfection):
Earlysexualintercourse

15. Risk factors for cervical neoplasia (2)
Multiplesexualpartners–having>6lifetimesexual
partnersimposesasignificant↑intherelativeriskofCaCx
Malepartnerwhohashadmultiplesexualpartners
Tobaccosmoking
Dietarydeficiencies–deficiencyofcertainvitaminslikeA,
C,E,betacarotene&folicacidmayaltercellular
resistancetoHPVinfection

16. Risk factors for cervical neoplasia (3)
Medical risk factors
Cervical high risk HPV
Exogenous hormones –COCs after using them for 5 yrs +
Parity
Immunosuppression (HIV, stress, smoking)
Inadequate screening

17. Why focus on cervical cancer? (1)
Worldwide,266000womendieofCaCxeachyear.
LeadingcauseofcancerdeathsinEasternandCentral
Africa.
CausesofCaCxareknown-almostallcasesare
causedbyapersistentinfectionwithoneormoreofthe
“high-risk”(oroncogenic)typesofHPV.

18. Why focus on cervical cancer? (2)
ThenaturalhistoryofHPVinfectionandtheveryslow
progressionofthediseaseinimmunocompetentwomen
isunderstood
The10to20-yearlagbetweenpre-cancerandcancer
offersampleopportunitytoscreen,detectandtreatpre-
cancerandavoiditsprogressiontocancer.
However,immunocompromisedwomen(e.g.thoseliving
withHIV)progressmorefrequentlyandmorequicklyto
pre-cancerandcancer

19. Why focus on cervical cancer? (3)
Thereareseveralavailableandaffordableteststhatcan
effectivelydetectpre-cancer,aswellasseveral
affordabletreatmentoptions.
HPVvaccinesarenowavailable
Ifthevaccinesaregiventogirlsbeforetheyaresexually
active,theycanpreventalargeportionofCaCx

20. What is cervical pre-cancer? (1)
Thisisadistinctchangeintheepithelialcellsofthe
transformationzoneofthecervix;
Thecellsbegindevelopinginanabnormalfashionin
thepresenceofpersistentorlong-termHPVinfection
Withthemajorityofcancers,eveniftheyhavea
precursorstage,itistooshorttobenoticedandnot
amenabletoeasydiagnosisandtreatment.

21. What is cervical pre-cancer? (2)
CaCxisoneoftheveryfewcancerswhereaprecursor
stage(pre-cancer)lastsmanyyearsbeforebecoming
invasivecancer,providingampleopportunityfor
detectionandtreatment
Unfortunately,althoughpreventable,therearestilllarge
numbersof♀whodieofCaCxinmanycountries
includingZambia
Thisisbecausetheylackaccesstoservicesfor
preventionandtreatment

22. The steps of cervical carcinogenesis

23. Infection with HPV
Persistent infection over 2-5yrs
progresses to precancer
Precancer
progresses to
invasive cancer
over 10-15
years

24. Histologic types
Squamouscellcarcinomas–70–80%
Keratinizingandnon-keratinizing
Adenocarcinomas–20%.Morehighriskintermsof
prognosis
Rareformsincludemalignantmelanomas,sarcomas,
lymphomasandsmallcellcarcinomas.
Mostofthesetumorspresentasbleedingcervicalmass

25. Spread (1)
Directorlocal:Downtovagina,anteriorlytobladder,
laterallytoparametriumandposteriorlytobowel
Withextensionthroughtheparametriatothepelvic
sidewall,ureteralblockagefrequentlydevelops,resultingin
hydronephrosis
Lymphaticspread–viatheparametrialnodestointernal,
externalandcommoniliacnodesandobturatornodes.
Presacralandpara-aorticlymphnodesmaybeinvolvedat
alaterstage

26. Spread (2)
Distantmetastasisresultsfromhaematogenous
dissemination
Thelungs,ovaries,liverandbonearethemostfrequently
affectedorgans

27. Clinical evaluation (1)
History
Postcoitalbleeding
Intermenstrualbleeding
Postmenopausalbleeding
Persistent,offensive,bloodstaineddischarge
Pain(latedisease)–lateraldirectspreadmayobstructthe
ureter,causingloinpainduetohydronephrosis.

28. Clinical evaluation (1)
Itmayaffectthesciaticnerve,causingpaininthe
buttockandbackoftheleg
Thrombosisinthepelvicveinsmaycauseaswollenleg
Examination
Speculum:Squamouscarcinomaspresentasexophytic,
friablelesions
Colposcopytoexaminethecervix

29. Clinical evaluation (2)
Hard,barrel-shapedcervix(morecommon with
adenocarcinomas)
Cervixmaybefixedinadvanceddisease
PR–hard,irregularmasspalpableanteriorly
Investigations:
1.Cervicalbiopsytoconfirmdiagnosis

30. Clinical evaluation (3)
2.Tostagedisease:
EUA
V/E-toassessthesizeofthelesion,parametrialorrectal
involvement.
Cystoscopydetectsbladderinvolvement
IVPtoexcludeuretericinvolvement.
X-rays,ultrasoundscan,CTscan,MRItoexcludedistant
metastasis.

31. Clinical evaluation (4)
3.Toassessfitnessforsurgeryandpretreatment
assessment
CXR,FBC,LFTs,U/E&Cr

32. Staging

37. Bladder
Rectum

38. Treatment(1)
EARLYDISEASE
1.StageIA
-Simplehysterectomyorcarefulobservationafterconebiopsy
(Withclearmargins).
2.StageIBorIIA
-Radical(Wertheim’s)hysterectomywithpelvic-node
dissection,or
-Externalbeamandintracavitaryradiotherapy(equally
effective

39. Treatment (2)
LATE DISEASE
3.StageIIB,III,IVA
-PelvicradiotherapyatCDH
-Treatmentwithcisplatin-basedchemotherapyshould
stronglybeconsideredforpatientsreceivingradiotherapy
4.StageIVB
-Treatmentispalliativeaimingtocontrolsymptoms
-Chemotherapywithorwithoutpelvicradiotherapy

40. Treatment (3)
Poorprognosticindicatorsare:
Lymphnodeinvolvement
Advancedclinicalstage,
Largeprimarytumour,
Apoorlydifferentiatedtumour
Deathiscommonlyfromuraemiaduetoureteric
obstruction

41. End
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