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CIN & Cervical Cancer. Women ’ s Hospital, School of Medicine, Zhejiang university. Cervical Intraepithelial Neoplasia (CIN). It is the premalignant disease related to the invasive cervical cancer Two different develop ways: fade naturely run to invasive cervical cancer.
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CIN & Cervical Cancer Women’s Hospital, School of Medicine, Zhejiang university
Cervical Intraepithelial Neoplasia (CIN) • It is the premalignant disease related to the invasive cervical cancer • Two different develop ways: fade naturely run to invasive cervical cancer
Cervical Cancer • 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 • Virus infection HPV HSV-II CMV • Early onset of sexual activity and multiple sexual partners • Sexual sanitation and multiparity • Others:oral contraceptive pill , smoking, immunodeficiency and so on
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 Bosch, et al. JNCI 1995
Occurring and development of CIN • Normal cervical epithelium squamous epithelium columnar epithelium • Squamo-columnar junction (SCJ) • originalSCJ • activeSCJ tranformation zone
Occurring and development of CIN Replace mechanisms of transformation zone • squamous metaplasia • 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 • 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 • 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 full-thickness(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.
Occurring and development of CIN Invasive cancers • Cells abnormality • Break the basement membrane and stroma involvement • Active stimulate factors is needed
Pathology CIN Cells abnormality arrange CIN I light disordered a little CIN II obviously disordered CIN III remarkably polarity disappeared
Pathology • Pathological types of invasive cervical cancers • Squamous cell:80-85% • adenocarcinoma:15-20% • Squamous cellsample • 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 • Invasive cancers :differentiated degree • 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 • Spread directly:frequently common • Lymph metastasis • Vascular metastasis :infrequency
Clinical Finding Symptoms: • vaginal bleeding :postcoital bleeding • 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: • 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 • History: postcoital bleeding • Physical examination • Biopsy:diagnose standard • Clinical staging
Assistant examination • 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) • Abnormal epithelium( require further evaluation ) • squamous epithelium • ASC-US and ASC-H • LSIL • HSIL • Adenoepithelium • AGC • Adenocarcinoma in site • Adenocarcinoma
Assistant examination HR-HPV-DNA test
Assistant examination • Schiller test: ①glycogen, which combines with iodine to produce a deep mahogany-brown color ② low special help to choose the sites for biopsy • Colposcopy: be required when reports of abnormal cells are made by former examinations.
Assistant examination • Biopsy: • diagnose standard • 3,6,9,12points of Squamo-columnar 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 )
Assistant examination Conization: • 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: • cold knife conization(CKC) • LEEP • laser
Differential diagnosis Cervical inflammation: cervical erosion cervical polypus Cervical mass: tuberculosis papilla tumor endometriosis
Therapy • depends on staging,age,common condition and medical equipment • Primary treatments:surgery and radiation • 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 • surgery therapy • radiation therapy • surgery concomitant radiation therapy • chemotherapy Radical treatment
Surgery therapy • Appropriates inthose: • Ia-IIa stage • without surgical forbiddance • can keep ovary function in young women • Ia1 hysterectomy • Ia2 -IIa Radical hysterectomy and therapeutic lymphadenectomy
Radiation therapy • abdominal cavity therapy • Back-install therapy machine • Early stage cases,to control local lesion • Outer body therapy • Beeline accelerator • Late stage cases • Pelvic LN and parametrial involvement
Radiation therapy • 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 Ibor before
Radiation therapy Complications : • 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 • Adaption:recurrence or late stage • Drugs: platinum,CTX,plant-alkali • Chemotherapy: • combination therapy • Squamous cell carcinomas:PVB,BIP • adenocarcinomas:PM,FIP • Approach:vein or artery perfusion
Follow-up • time: • 2 years ,once each 3month • 3-5 years, once each 6month • >6years,once every year • content: • PV • Cytological examination of residual vagina • Chest X-Ray • Blood RT