CIN & Cervical Cancer
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Transcript of CIN & Cervical Cancer
CIN & Cervical CancerCIN & Cervical Cancer
WomenWomen’’s Hospital, School of Medicine, s Hospital, School of Medicine, Zhejiang universityZhejiang university
Cervical Intraepithelial Cervical Intraepithelial Neoplasia (CIN) Neoplasia (CIN)
It is the premalignant disease related It is the premalignant disease related to the invasive cervical cancerto the invasive cervical cancer
Two different develop ways:Two different develop ways:
fade naturelyfade naturely
run to invasive cervical cancerrun to invasive cervical cancer
Cervical CancerCervical Cancer It is the most common type of gynecologic It is the most common type of gynecologic
cancerscancers The incidence and mortality of cervical The incidence and mortality of cervical
cancer have continued to declinecancer have continued to decline
Reasons : Reasons :
●●A long time of the premalignant stageA long time of the premalignant stage
●● Cervix cytologic examinationCervix cytologic examination
Estimated New Cancer Cases and Deaths by Sex,United States,
2011
Jemal A,et al.CA Cancer J Clin 2011
Estimated New Cancer Cases and Deaths by Sex,United States,
2011
Jemal A,et al.CA Cancer J Clin 2011
EtiologyEtiology
Virus infectionVirus infection HPV HSV-IIHSV-II CMVCMV Early onset of sexual activity and Early onset of sexual activity and multiple sexual partnersmultiple sexual partners Sexual sanitation and multiparity Sexual sanitation and multiparity OthersOthers :: oral contraceptive pill , smoking, oral contraceptive pill , smoking,
immunodeficiency and so on immunodeficiency and so on
HPV HPV --------prime etiologic prime etiologic factorfactor
• More than 100 types of HPVMore than 100 types of HPV
• About 35 types associated with About 35 types associated with
genital infectiongenital infection
• About 20 types associated with About 20 types associated with
cancercancer
• 13 high-risk type of cancer 13 high-risk type of cancer
associated:associated:
16, 18, 31, 33, 35, 39, 45, 51, 16, 18, 31, 33, 35, 39, 45, 51,
52, 56, 58, 59, 6852, 56, 58, 59, 68
• Low-risk type:6,11,40,42,43,44Low-risk type:6,11,40,42,43,44
Prevalence of HPV Genotypes in Invasive
Cancers
Prevalence of HPV Genotypes in Invasive
Cancers
0 100 200 300 400 500
Number of Invasive Cancers
P291
HPV 6
HPV 11
HPV 55
HPV 26
P238A
W13B
HPV 51
HPV 68
HPV 39
HPV 59
HPV 35
HPV 56
HPV 58
HPV 52
HPV 33
HPV 31
HPV 45
HPV 18
HPV 16
Bosch, et al. JNCI 1995
Occurring and development Occurring and development of CINof CIN
Normal cervical epitheliumNormal cervical epithelium
squamous epithelium squamous epithelium
columnar epitheliumcolumnar epithelium Squamo-columnar junction (SCJ)Squamo-columnar junction (SCJ)
originaloriginal SCJSCJ activeactive SCJSCJ
tranformation zonetranformation zone
Replace mechanisms of transformation Replace mechanisms of transformation zonezone
squamous metaplasiasquamous metaplasia Undifferentiation reserve cells under Undifferentiation reserve cells under
columnar epithelium hyperplasy and changecolumnar epithelium hyperplasy and change Most of the squamous cells are immaturity Most of the squamous cells are immaturity Squamous metaplasia of the glandSquamous metaplasia of the gland :: gland gland
cells replaced by the squamous epithelium cells replaced by the squamous epithelium squamous epithelization squamous epithelization
squamous epithelium enters and replaces squamous epithelium enters and replaces directlydirectly
squamous epithelization cells are completely squamous epithelization cells are completely similar with the squamous epitheliumsimilar with the squamous epithelium
Most appears in the concrescence of cervical Most appears in the concrescence of cervical erosionerosion
Occurring and development of Occurring and development of CINCIN
CIN means disordered growth and CIN means disordered growth and development of the epithelial lining of the development of the epithelial lining of the cervix cervix grade Igrade I :: the lower third of the epithelial lining the lower third of the epithelial lining grade IIgrade II :: two-thirds of the lining two-thirds of the lining grade IIIgrade III :: more than two-thirds of the lining or more than two-thirds of the lining or
full-thicknessfull-thickness((carcinoma in situ carcinoma in situ )) CINI: 60% regress to normal, 30% persistent, CINI: 60% regress to normal, 30% persistent,
10%have disease progression to CINIII10%have disease progression to CINIII CIN progress to cancer may take 10 to 15 yearsCIN progress to cancer may take 10 to 15 years Those metaplasia squamous epithelium can Those metaplasia squamous epithelium can
develop to invasive cancers directly. develop to invasive cancers directly.
Occurring and development Occurring and development of CINof CIN
Invasive cancersInvasive cancers
Cells abnormalityCells abnormality Break the basement membrane Break the basement membrane
and stroma involvementand stroma involvement Active stimulate factors is Active stimulate factors is
neededneeded
Occurring and development Occurring and development of CINof CIN
PathologyPathology
CINCIN
Cells abnormality arrangeCells abnormality arrange
CIN I light CIN I light disordered a little disordered a little
CIN II obviously CIN II obviously disordereddisordered
CIN III remarkably polarity CIN III remarkably polarity disappeareddisappeared
PathologyPathology
Pathological types of invasive cervical Pathological types of invasive cervical cancerscancers Squamous cellSquamous cell :: 80-8580-85 %% adenocarcinomaadenocarcinoma :: 15-2015-20 %%
Squamous cellSquamous cell samplesample CIN and early-stage CIN and early-stage of invasive cervical of invasive cervical
cancers looks like the cervical erosioncancers looks like the cervical erosion Four types of Four types of invasive cervical cancersinvasive cervical cancers
outer-growthouter-growth endogenesisendogenesis cankerouscankerous cervix canalcervix canal
PathologyPathologyMicroscope:Microscope: Early invasive cancers under microscopeEarly invasive cancers under microscope
Ia1 depth≤3 mmIa1 depth≤3 mm ,, width≤ 7mmwidth≤ 7mm Ia2 depth3Ia2 depth3 -- 5mm5mm ,, width≤ 7mmwidth≤ 7mm
Invasive cancers Invasive cancers :: differentiated differentiated degreedegree Grade IGrade I : : large cell keratinizing typelarge cell keratinizing type keratinizationkeratinization , , fewer than 2 fewer than 2
mitoses/HPmitoses/HP Grade IIGrade II : : large cell nonkeratinizing typelarge cell nonkeratinizing type moderate keratinization moderate keratinization ,, 2-4 2-4
mitoses/HP mitoses/HP Grade IIIGrade III :: small cell carcinomassmall cell carcinomas poor differentiatedpoor differentiated ,, more than 4 more than 4
mitoses/HPmitoses/HP
Metastasis pathwayMetastasis pathway
Spread directlySpread directly :: frequently frequently commoncommon
Lymph metastasisLymph metastasis
Vascular metastasis Vascular metastasis ::infrequencyinfrequency
Staging
Clinical FindingClinical Finding
SymptomsSymptoms :: vaginal bleeding vaginal bleeding :: postcoital postcoital
bleeding bleeding Menstruate disordered in young womenMenstruate disordered in young women Abnormal vaginal bleeding in eldersAbnormal vaginal bleeding in elders
vaginal liquiding vaginal liquiding Pelvic painPelvic pain the late stages the late stages :: metastastic metastastic
symptomssymptoms weakness, weight loss, and anemiaweakness, weight loss, and anemia
Clinical FindingClinical Finding
SignsSigns ::
A grossly normal-appearing A grossly normal-appearing cervix with CIN or early stage cervix with CIN or early stage invasive cancersinvasive cancers
Signs may be related to the Signs may be related to the growth types growth types
Metastatic signs in the late Metastatic signs in the late stagesstages
DiagnoseDiagnose
HistoryHistory : : postcoital bleedingpostcoital bleeding Physical examinationPhysical examination BiopsyBiopsy :: diagnose standarddiagnose standard Clinical stagingClinical staging
Assistant examinationAssistant examination Cervical cytologyCervical cytology
pap pap
smearsmear
TCTTCT
Assistant examinationAssistant examination
Pap smearsPap smears :: II : : normalnormal IIII : : inflammationinflammation IIIIII : : suspicionsuspicion IVIV :: highly suspicionhighly suspicion VV : : malignantmalignant II considered as inflammationII considered as inflammation Ⅲ Ⅲ to Ⅴrequire further to Ⅴrequire further
evaluation.evaluation.
Assistant examinationAssistant examinationThe Bethesda System (TBS)The Bethesda System (TBS) Abnormal epitheliumAbnormal epithelium ( ( require require
further evaluation further evaluation )) squamous epithelium squamous epithelium
ASC-US and ASC-HASC-US and ASC-H LSILLSIL HSILHSIL
AdenoepitheliumAdenoepithelium AGCAGC Adenocarcinoma in siteAdenocarcinoma in site AdenocarcinomaAdenocarcinoma
Assistant examinationAssistant examination
Schiller testSchiller test :: ①①glycogen, which combines with iodine glycogen, which combines with iodine
toto
produce a deep mahogany-brown produce a deep mahogany-brown colorcolor
② ② low speciallow special
help to choose the sites for biopsyhelp to choose the sites for biopsy ColposcopyColposcopy :: be required when reports of abnormal be required when reports of abnormal
cells are made by former examinations.cells are made by former examinations.
Assistant examinationAssistant examination
BiopsyBiopsy :: diagnose standarddiagnose standard 33 ,, 66 ,, 99 ,, 12points of 12points of Squamo-Squamo-
columnar junctioncolumnar junction suspicion sites by Schiller test or suspicion sites by Schiller test or
ColposcopyColposcopy Sample requires epithelium and Sample requires epithelium and
stromastroma endocervical curettage is endocervical curettage is
necessary(abnormal cervical cytology necessary(abnormal cervical cytology smearsmear , ,cervix smooth or biopsy cervix smooth or biopsy negative )negative )
Assistant examinationAssistant examinationConization:Conization:
Abnormal cervical cytological Abnormal cervical cytological examination ,negative biopsyexamination ,negative biopsy
a biopsy revealing carcinoma in situ, a biopsy revealing carcinoma in situ, where invasion cannot be ruled outwhere invasion cannot be ruled out
Tissues be divided into 12 pieces ,each Tissues be divided into 12 pieces ,each piece includes 2-3 slices.piece includes 2-3 slices.
meansmeans :: cold knife conization(CKC)cold knife conization(CKC) LEEPLEEP laserlaser
CKC
Differential diagnosisDifferential diagnosis
Cervical inflammation:Cervical inflammation:
cervical erosioncervical erosion
cervical polypuscervical polypus
Cervical mass:Cervical mass:
tuberculosis tuberculosis
papilla tumorpapilla tumor
endometriosisendometriosis
TherapyTherapy
depends on staging,age,common depends on staging,age,common condition and medical equipmentcondition and medical equipment
Primary treatmentsPrimary treatments :: surgery and surgery and radiationradiation approximately equalapproximately equal with different complicationswith different complications
The role of chemotherapy has been The role of chemotherapy has been newly evaluatednewly evaluated
TreatmentTreatment
CINCIN :: Grade IGrade I : : expectant management, follow up every 3 to 6 expectant management, follow up every 3 to 6
months.biopsy again if necessary or months.biopsy again if necessary or conization(excise the lesion)conization(excise the lesion)
Grade IIGrade II :: cryo or laser or conizationcryo or laser or conization ,, follow up follow up
every 3to6 monthsevery 3to6 months Grade III: Grade III: conization or conization or hysterectomyhysterectomy
Treatment of invasive cervical Treatment of invasive cervical carcinomacarcinoma
surgery therapysurgery therapy radiation therapyradiation therapy surgery concomitant surgery concomitant
radiation therapyradiation therapy chemotherapychemotherapy
Radical treatment
Surgery therapySurgery therapy Appropriates inAppropriates in those:those:
Ia-IIa stageIa-IIa stage without surgical forbiddancewithout surgical forbiddance can keep ovary function in young womencan keep ovary function in young women
Ia1Ia1 hysterectomyhysterectomy Ia2 -IIaIa2 -IIa Radical hysterectomy and Radical hysterectomy and
therapeutictherapeutic lymphadenectomylymphadenectomy
Radical hysterectomyRadical hysterectomy
Radiation therapyRadiation therapy
abdominal cavity therapyabdominal cavity therapy Back-install therapy machineBack-install therapy machine Early stage cases,to control local Early stage cases,to control local
lesionlesion Outer body therapyOuter body therapy
Beeline acceleratorBeeline accelerator Late stage casesLate stage cases Pelvic LN and Pelvic LN and parametrial parametrial
involvementinvolvement
Radiation therapyRadiation therapy
Radiation therapy aloneRadiation therapy alone : IIb : IIb toⅣb stagetoⅣb stage
Postoperative adjuvant radiationPostoperative adjuvant radiation :: positive lymph nodespositive or positive lymph nodespositive or close resection margins, or close resection margins, or parametrial involvementparametrial involvement
PreoperativelyPreoperatively :: large tumor size large tumor size of stage Ibof stage Ib or beforeor before
Radiation therapyRadiation therapy
ComplicationsComplications : : radiocystitis and radiorectitisradiocystitis and radiorectitis divide into near and future datesdivide into near and future dates
The former can recover by itselfThe former can recover by itself The later will develop to The later will develop to
ulcer,hemorrhage, straitness and ulcer,hemorrhage, straitness and fistula after 1-3yearsfistula after 1-3years
Be related to the radiation dose and Be related to the radiation dose and positionposition
ChemotherapyChemotherapy
AAdaptiondaption :: recurrence or late recurrence or late stagestage
Drugs:Drugs:
platinumplatinum ,, CTXCTX ,, plant-alkaliplant-alkali ChemotherapyChemotherapy ::
combination therapycombination therapy Squamous cell carcinomasSquamous cell carcinomas ::
PVBPVB ,, BIPBIP adenocarcinomasadenocarcinomas :: PMPM ,, FIPFIP
ApproachApproach :: vein or artery vein or artery perfusionperfusion
Follow-upFollow-up
timetime :: 2 years 2 years ,, once each 3monthonce each 3month 3-5 years3-5 years , , once each 6monthonce each 6month >6years>6years ,, once every yearonce every year
contentcontent : : PVPV Cytological examination of Cytological examination of
residual vaginaresidual vagina Chest X-RayChest X-Ray Blood RTBlood RT