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CIN & Cervical Cancer
Women’s Hospital, School of Medicine, Zhejiang university
Cervical Intraepithelial Neoplasia
(CIN)
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It is the premalignant disease related to the
invasive cervical cancer
Two different develop ways:
fade naturely
run to invasive cervical cancer
Cervical Cancer
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It is the most common type of gynecologic cancers
The incidence and mortality of cervical cancer have
continued to decline
Reasons :
●A long time of the premalignant stage
● Cervix 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
Etiology
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Virus infection
HPV
HSV-II
CMV
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Early onset of sexual activity and
multiple sexual partners
Sexual sanitation and multiparity
Others：oral contraceptive pill , smoking,
immunodeficiency and so on
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HPV ----prime etiologic factor
•
More than 100 types of HPV
•
About 35 types associated with genital
infection
•
About 20 types associated with cancer
•
13 high-risk type of cancer associated:
16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59,
68
•
Low-risk type:6,11,40,42,43,44
Prevalence of HPV Genotypes in
Invasive Cancers
HPV 16
HPV 18
HPV 45
HPV 31
HPV 33
HPV 52
HPV 58
HPV 56
HPV 35
HPV 59
HPV 39
HPV 68
HPV 51
W13B
P238A
HPV 26
HPV 55
HPV 11
HPV 6
P291
0
100
200
300
400
500
Number of Invasive Cancers
Bosch, et al. JNCI 1995
Occurring and development of CIN
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Normal cervical epithelium
squamous epithelium
columnar epithelium
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Squamo-columnar junction (SCJ)
 original SCJ
tranformation zone
 active SCJ
Occurring and development of CIN
Replace mechanisms of transformation zone
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squamous metaplasia
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Undifferentiation reserve cells under columnar
epithelium hyperplasy and change
Most of the squamous cells are immaturity
Squamous metaplasia of the gland：gland cells
replaced by the squamous epithelium
squamous epithelization
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squamous epithelium enters and replaces directly
squamous epithelization cells are completely similar
with the squamous epithelium
Most appears in the concrescence of cervical erosion
Occurring and development of CIN
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CIN means disordered growth and development of
the epithelial lining of the cervix
grade I：the lower third of the epithelial lining
 grade II：two-thirds of the lining
 grade III：more than two-thirds of the lining or fullthickness(carcinoma in situ )
CINI: 60% regress to normal, 30% persistent, 10%have
disease progression to CINIII
CIN progress to cancer may take 10 to 15 years
Those metaplasia squamous epithelium can develop to
invasive cancers directly.
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Occurring and development of CIN
Invasive cancers
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Cells abnormality
Break the basement membrane and stroma
involvement
Active stimulate factors is needed
Pathology
CIN
CIN I
CIN II
CIN III
Cells abnormality
arrange
light
disordered a little
obviously
remarkably
disordered
polarity disappeared
Pathology
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Pathological types of invasive cervical cancers
 Squamous cell：80-85％
 adenocarcinoma：15-20％
Squamous cell sample
 CIN and early-stage of invasive cervical cancers looks
like the cervical erosion
 Four types of invasive cervical cancers
outer-growth
endogenesis
cankerous
cervix canal
Pathology
Microscope:
 Early invasive cancers under microscope
Ia1 depth≤3 mm，width≤ 7mm
 Ia2 depth3－5mm，width≤ 7mm
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Invasive cancers ：differentiated degree
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Grade I： large cell keratinizing type
keratinization， fewer than 2 mitoses/HP
Grade II： large cell nonkeratinizing type
moderate keratinization ，2-4 mitoses/HP
Grade III：small cell carcinomas
poor differentiated，more than 4 mitoses/HP
Metastasis pathway
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Spread directly：frequently common
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Lymph metastasis
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Vascular metastasis ：infrequency
Staging
Clinical Finding
Symptoms：
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vaginal bleeding ：postcoital bleeding
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Menstruate disordered in young women
Abnormal vaginal bleeding in elders
vaginal liquiding
Pelvic pain
the late stages ：metastastic symptoms
weakness, weight loss, and anemia
Clinical Finding
Signs：
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A grossly normal-appearing cervix with
CIN or early stage invasive cancers
Signs may be related to the growth types
Metastatic signs in the late stages
Diagnose
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History： postcoital bleeding
Physical examination
Biopsy：diagnose standard
Clinical staging
Assistant examination
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Cervical cytology
pap
smear
TCT
Assistant examination
Pap smears：
I： normal
II： inflammation
III： suspicion
IV：highly suspicion
V： malignant
II considered as inflammation
Ⅲ to Ⅴrequire further evaluation.
Assistant examination
The Bethesda System (TBS)
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Abnormal epithelium（ require further
evaluation ）
 squamous epithelium
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ASC-US and ASC-H
LSIL
HSIL
Adenoepithelium
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AGC
Adenocarcinoma in site
Adenocarcinoma
Assistant examination
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Schiller test ：
①glycogen, which combines with iodine to
produce a deep mahogany-brown color
② low special
help to choose the sites for biopsy
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Colposcopy ：
be required when reports of abnormal cells
are made by former examinations.
Assistant examination
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Biopsy：
diagnose standard
 3，6，9，12points of Squamo-columnar
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junction
suspicion sites by Schiller test or
Colposcopy
 Sample requires epithelium and stroma
 endocervical curettage is
necessary(abnormal cervical cytology
smear ,cervix smooth or biopsy negative )
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Assistant examination
Conization:
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Abnormal cervical cytological examination ,negative
biopsy
a biopsy revealing carcinoma in situ, where invasion
cannot be ruled out
Tissues be divided into 12 pieces ,each piece
includes 2-3 slices.
means：
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cold knife conization(CKC)
LEEP
laser
CKC
Differential diagnosis
Cervical inflammation:
cervical erosion
cervical polypus
Cervical mass:
tuberculosis
papilla tumor
endometriosis
Therapy
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depends on staging,age,common condition and
medical equipment
Primary treatments：surgery and radiation
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approximately equal
with different complications
The role of chemotherapy has been newly
evaluated
Treatment
CIN：
Grade I：
expectant management, follow up every 3 to 6 months.biopsy
again if necessary or conization(excise the lesion)
Grade II：
cryo or laser or conization ，follow up every 3to6
months
Grade III:
conization or hysterectomy
Treatment of invasive cervical
carcinoma
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surgery therapy
Radical
radiation therapy
treatment
surgery concomitant radiation therapy
chemotherapy
Surgery therapy
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Appropriates in those:
 Ia-IIa stage
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without surgical forbiddance
can keep ovary function in young women
Ia1
hysterectomy
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Ia2 -IIa
Radical hysterectomy and therapeutic
lymphadenectomy
Radical hysterectomy
Radiation therapy
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abdominal cavity therapy
Back-install therapy machine
 Early stage cases,to control local lesion
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Outer body therapy
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Beeline accelerator
Late stage cases
 Pelvic LN and parametrial involvement
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Radiation therapy
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Radiation therapy alone : IIb toⅣb stage
Postoperative adjuvant radiation : positive
lymph nodespositive or close resection
margins, or parametrial involvement
Preoperatively ：large tumor size of stage Ib
or before
Radiation therapy
Complications :
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radiocystitis and radiorectitis
divide into near and future dates
 The former can recover by itself
 The later will develop to ulcer,hemorrhage,
straitness and fistula after 1-3years
Be related to the radiation dose and position
Chemotherapy
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Adaption：recurrence or late stage
Drugs:
platinum，CTX，plant-alkali
Chemotherapy ：
combination therapy
 Squamous cell carcinomas ：PVB，BIP
 adenocarcinomas ：PM，FIP
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Approach ：vein or artery perfusion
Follow-up
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time：
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2 years ，once each 3month
3-5 years， once each 6month
>6years，once every year
content：
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PV
Cytological examination of residual vagina
Chest X-Ray
Blood RT