CERVICAL CANCER.ppt

Cancer

1. PREMALIGNANT LESION OF THE
CERVIX AND CERVICAL CANCER:
PRESENTATION, PREVENTION
AND MANAGEMENT
DR ADULOJU OLUSOLA PETER
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,
EKITI STATE UNIVERSITY,
ADO-EKITI

2. PREMALIGNANT LESIONS OF THE CERVIX
Premalignantlesionofthecervixisalsoknown
ascervicalintra-epithelialneoplasia(CIN)
Theyareprecursorlesionswhichhavea
significantpotentialtobecomeaninvasive
malignantlesion
Mostoftheselesionsareusuallyasymptomatic
andareofclinicalimportancebecausetheymay
progresstoinvasivemalignancies

3. DEFINITION OF TERMS
Squamo-columnarjunction(SCJ):Thisisthe
pointofintersectionbetweenthecolumnarand
thesquamousepithelium.Animportant
landmarkforneoplasticchanges.
Transformationzone(TFZ):Partofthe
columnarepitheliumofthecervixundergoes
squamousmetaplasia.Themetaplasticareaand

4. andcolumnarepitheliumformtheTFZ.Over95%
ofalltheCINlesionsarisefromthiszone

5. SCJ &TFZ

6. PREMALIGNANT LESIONS AND HUMAN
PAPILLOMA VIRUS (HPV)
HPVhasbeenimplicatedinthepathogenesisof
premalignantlesionsofthefemalegenitaltract
HPVaredoublestrandedDNAviruses
Theviralgenomehas3regions
Theupstreamregulatoryregioninvolvedinviral
replicationandcontroloftranscription
TheearlygenesresponsibleforDNAreplication,

7. transcriptionalregulationandtransformation
(E1,E2,E3,E4,E5,E6,E7).E6andE7encodefor
majortransformingproteinscapableofinducing
cellproliferationandimmortalizationbybinding
totumorsuppressorgeneproductsp53andpRB
Thelategenes(L1,L2)controlformationof
capsid(virus)coat
HPVinfectionisasexuallytransmittedinfection
andoccursinbetweenthesexes

8. Over100typesofHPVhavebeenidentifiedand
classifiedinto:
Lowrisk6&11causepapillomaoftheupper
airwaysandexternalgenitalcondyloma
Intermediaterisk31,33,35,51&52are
associatedwithdysplasia
Highrisk16&18associatedwithhighandlow
gradesquamouslesionsrespectively

9. EPIDEMIOLOGY OF CIN
Multiplesexualpartners
Earlycoitarche
Earlymarriage
Malepartnerwithpreviousmultiplefemale
sexualpartners
Lowsocio-economicstatus
Oralcontraceptivepills
Cigarettesmoking

10. GRADING OF CIN
Histologicgradingbasedontheproportionof
theepitheliumoccupiedbydysplasticcells
Cytologicgradingbasedontheseverityof
dysplasiaintheepithelium
Bothgradinguseathreetiersystem
CINI(Milddysplasia):Dysplasticcellsoccupy
thelowerthirdoftheepithelium
CINII(Moderatedysplasia):Dysplasticcells
occupythelowertwo-thirdsoftheepithelium

11. CINIII(Severedysplasia,carcinomainsitu):
Dysplasticcellsextendintotheupperthirdand
mayoccupythefullthicknessoftheepithelium
TheBethesdasystem:Usesatwotiersystem
Lowgradesquamousintra-epitheliallesion
(LGSIL)HPVchangesonsmearsandCINI
Highgradesquamousintra-epitheliallesion
(HGSIL)CINIIandCINIII/Cainsitu

12. NATURAL HISTORY OF CIN LESIONS
LESIONREGRESSPERSISTPROGRESS TO
CINIII
PROGRESS TO
INVASIVE CANCER
CIN 160% 30% 5-8% 1%
CIN II43% 35% 8-10% 12% progressto
CIS or invasive Ca
CIN III32% 54% - 14%

13. SCREENING FOR CIN
Cervicalcanceristheonlygynecologiccancer
that’samenabletoextensivescreeningandthis
hasreduceditsdeathratetoabout70%
Cervixiseasilyaccessibleandexfoliativecellscan
easilybeobtained
Thediseasehasawelldefinedpre-clinicalstage
Thescreeningmethodsaresimpleandcheap
Treatmentsareavailableforthepre-clinicalstage

14. SCREENING METHODS
PAPsmeartest:
Cervicalspecimenaretakenbywoodenorplastic
spatulaorcytobrush(traditionally).Thespecimenis
smearedonaglassslideandfixedinalcohol
Liquidbasedmethodhasimprovedthesensitivityof
thetest.Thebrushisbroken,thepartwiththe
specimenisdroppedinabottlecontaining
preservativeandsenttothelaboratory

15. Visualinspectionofthecervixunaided:Also
referredtoasclinicaldownstagingandaimisto
detectabnormal/suspiciouslookingcervix.
Abnormalityincludes:Hypertrophy,irregular
surface,distortionorerosionofthecervix
VisualinspectionofthecervixwithAceticacid:
Thecervixisswabbedwith3-5%AceticAcid
priortovisualization
Abnormalcellsturnwhite(aceto-white)dueto

16. highnuclearcontent
VisualinspectionwithLugol’sIodine:Also
knownasSchiller’stest.Thecervixisswabbed
Iodineandtheabnormalareasturnsyellowdue
tolackofglycogen

17. Visual inspection of the cervix unaided
Normal looking cervixAbnormal looking cervix

18. Visual inspection of the cervix aided
Aided with 3-5% Acetic acidAided with Lugol’s Iodine

19. MANAGEMENT OF ABNORMAL PAP
SMEAR
Thiscouldbemild,moderateorsevere
dysplasiaoncytology(celldiagnosis)
Referforcolposcopywithaceticacidand
Lugol’siodinetoidentifytheabnormalarea
Colposcopicallydirectedbiopsyofabnormal
lookingspotforhistology(tissuediagnosis)

20. HistologymaybeHPVchanges,CINI,CINIIor
CINIII
Treatmentoptionsavailableinclude:
CINI(LGSIL):
Followupwithfrequentcytologyscreening(4-
6months)
Referforcolposcopyifdysplasiapersistsor
worsensandthentreat
Reverttoroutinescreeningiftestbecomes

21. normal
CINIIandCINIII(HGSIL):Offer
Localablativetreatment-cryotherapy,CO2laser
therapy,electrocauteryandthermalablation
Tissuedestructionistoadepthof8mm
Theablativetherapydoesnotyieldanytissue
forhistologicaldiagnosis
Sideeffectarecramping,pain,waterydischarge

22. Excisionaltreatment-conisation,loop
electrosurgicalexcisionprocedure(LEEP)or
largeloopexcisionoftransformationzone
(LLETZ)andhysterectomy
Providestissueforhistologicaldiagnosis
Complicationsincludebleeding,cervical
stenosis,incompetenceanddystociainlabour
FollowupisdonewithPapsmearsand
colposcopyaftertherapy

23. INTRODUCTION
Cervicalcancerconstitutesamajorpublichealth
threattowomeninmanylowandmiddle
incomecountriesincludingsub-SaharanAfrica
2
nd
mostcommoncanceramongwomen
worldwideandcommonestcauseofcancer
relatedmorbidityandmortality
Commonestfemalegenitaltractcancerandit

24. accountsforover70%ofgynaecologicalcancers
Over500,000newcasesand250,000deaths
eachyear,80%ofwhichoccurinthelowincome
countries
Theincidenceandmortalityofcervicalcancer
havefalleninthehighincomecountriesduetoa
wellestablishedscreeningprograms
Cervicalcancerisadetectableandpreventable
disease

25. Hasapre-existinglesioncalledcervical
intraepithelialneoplasia(CIN)
Associationbetweencervicalcancerand
humanpapillomavirushasbeenestablished
Cervicalcancercasesaredirectlylinkedto
previousinfectionswithoneormoreoncogenic
strainsofHPV(especiallyHPV16&18)
Cervicalcancerisnowconsideredasoneofthe
AIDSdefininglesions

26. EPIDEMIOLOGICAL RISK FACTORS
Highriskbehaviorassociated
Earlycoitarche
Earlymarriage
Multiplechildbirth
Highriskhusband-husbandthatispromiscuous.
Hascancerofthepenisorhasconsortswith
cervicalcancer
Immunosuppression-Itenhancesviral

27. persistenceinhostcervicalcells
Epidemiologicalfactors
Familialpredisposition
Cigarettesmoking
Useofcombinedoralpills
Age-Meanageis51.4yearsbuthastwopeak
incidences(30-39yearsand60-69years)
Race–commoneramongtheblackrace
Lowsocio-economicstatus

28. HISTOLOGICAL TYPES
Squamouscellcarcinoma(85-90%)
Adenocarcinoma(10-15%)
Mixed-adeno-squamous,glassycell
Others-lymphoma,melanoma,sarcoma

29. Typesofgrowth
Endophyticorulcerativegrowth
Exophyticorcauliflowergrowth
Spread
Directextension-localspreadtotheuterine
body,uppervagina,bladder,rectum,broad
ligamentanduterosacralligament
Lymphaticspread
Haematogenousspread-rarely

30. COMPLICATIONS OF CA CERVIX
Pyometraduetoendocervicalobstruction
Vesico-vaginalfistuladuetobladderinvasion
Recto-vaginalfistuladuetorectalinvasion
Uretericobstructionwithhydroureter,
hydropelvis,hydronephrosisandpyonephrosis
Uraemia
Haemorrhage
Cachexia

31. CLINICAL PRESENTATION
Asymptomatic-discoveredduringscreening(CIS
Symptomatic
Bleeding-irregular,recurrent,post-coital
Vaginaldischarge-purulentandmalodorous
Inadvancedcases
Cachexia
Micturitionsymptoms-dysuria,frequency
Rectalsymptomssuchaspains

32. Pains-lowbackache,deeppelvicache,sciatica,
uretericcolic
Pedaledema
Physicalsigns
Cervicallesion-maybeulcerativeorfungating
Diagnosis
AbnormalPAPsmear-colposcopyandbiopsy
Endo-orexophyticlesions-Cervicalbiopsydone
withTischlerbiopsyforcep

33. EVALUATION
Fullbloodcount
Renalfunctiontests
Chestradiograph
Electro-cardiogram
Intravenousurography(usedinstaging)
Examinationunderanaesthesia,stagingand
cervicalbiopsy

34. FIGO STAGING OF CERVICAL CANCER
Stage 1: Disease is limited to the cervix
Stage 2: Involvement of the upper 2/3
rd
of the
vaginal and parametrium
Stage 3: Involvement of the lower 1/3
rd
of the
vaginal, pelvic side wall and bilateral
hydronephrosis /non functioning kidneys
Stage 4: Distant metastasis (bladder, rectum…)

35. FIGO STAGING OF CERVICAL CANCER

36. TREATMENT
Aimsattreatingboththeprimarytumorandthe
potentialmetastaticareas.
Treatmentmodalitiesinclude:
Surgery
Radiotherapy
Combinationofboth
Adjuvantchemotherapyandradiotherapy
(chemo-radiation)

37. Choiceoftreatmentdependon
Thestageofthedisease
Availablefacilitiesandpersonnelsincluding
oncologicalsurgeons
Presenceofotherpatients’factorslike
advancedage,bleeding,priorsurgery
1.CIN/carcinomainsitu:Ablativeandexcisional
2.StageIA1:Hysterectomy
3.StageIA2:Conebiopsy,simplehysterectomy

38. andpelviclymphadenectomy
4.StageIB1&IIA:Extendedabdominal
hysterectomywithbilateralpelvic
lymphadenectomy
5.StageIB2,2B-4B:
Radiotherapy-Intracavitaryirradiation
(Brachytherapy)tolesionandexternalbeam
irradiation(Teletherapy)tothepelvicsidewall
andpara-aorticarea

39. Combinedchemotherapyandradiation(chemo-
radiation)treatmentmaybeoffered.Cisplatin
hasbeenfoundmosteffectivecytotoxicagent
inthetreatmentofcervicalcancer
CausesofdeathinCervicalcancer
Haemorrhage-painless
Uraemia-becomesunconscious
Cachexia-associatedwithrecurrent
haemorrhage

40. PREVENTION OF CERVICAL CANCER
Primaryprevention
Educationandawarenessofdisease
Modifylifestyleandsocialhabits(multiple
sexualpartners,smokingetc)
Useofbarriermethodofcontraception
HPVtestingandvaccinationforyounggirls(9-
12yrs)-Bivalentandquadrivalentvaccines
Establishmentofcervicalscreeningprogram

41. Secondaryprevention
Cervicalscreeningwithpapsmear
Colposcopyanddirectedbiopsy
TreatmentofCIN
FollowupaftertreatmentofCIN
Tertiary
Management ofcervicalcancerand
complications

42. GLOBAL STRATEGY AGAINST CERVICAL CANCER
Cervicalcancerremainsapreventabledisease
Itiscurableifdetectedearlyandadequately
treated
However,itremainsoneofthemostcommon
cancersandcausesofcancer-relateddeathin
womenacrosstheglobe
Morethan85%ofthoseaffectedareyoung,
uneducatedandliveinlowincomecountries
Manyarealsomothersofyoungchildren
whosesurvivalistruncatedbymother’sdeath

43. Provenandcosteffectivemeasuresfor
eliminatingcervicalcancerexist
Implementationispoorespeciallyinregionsof
theworldwithhighestdiseaseburden
Theremustbeastrategicactiontowards
eliminatingcervicalcancerasapublichealth
problem
Theglobalstrategytoeliminatecervicalcancer
wasrecentlylaunchedbyWHOasaconcerted
efforttoreducetheburdenofcervicalcancerall
overtheworld

44. This strategy proposes:
A vision of a world where cervical cancer is
eliminated as a public health problem
The following 90-70-90 targets that must be
met by 2030 for countries to be on the path
towards cervical cancer elimination:
90% of girls fully vaccinated by age 15 years
70% of women are screened with a high
performance test by 35 years of age and again
by 45 years of age
90% of women identified with cervical disease
receive treatment (pre-cancer & invasive ca)