Cervical Cancer

Xin LU

OB/GYN Hospital Fudan University

ContentsGeneral informationCINs Spread pattern FIGO staging Clinical signsDiagnosis and differential diagnosis Principle for treatmentPreventionSurveillance

Key wordsCervical cancer (Cxca)Human Papillomavirus (HPV)Radical Hysterectomy (RH)Radiotherapy (RT)Chemotherapy (CT)Neoadjuvant chemotherapy (NACT) Concurrent chemo-radiotherapy (CCCR)Radical Trachelectomy

Female Reproductive Anatomy

Cervical Cancer World report: Account for 1/3 female malignanciesNew cases: 529 800Death: 275 10085% developing country

The 4th most common cause of death from malignancy in women.

Cxca Progression

HPV infection CINs Carcinoma in situ 10-15yr Cervical cancer

EtiologyHigh-risk factorsHR-HPVUse of oral contraceptivesSmoking Multiple sexual partnersHistory of herpes infection History of STD

Human Papillomavirus , HPV

1972Harald zur Hausen Zur Hausen

1995High-risk HPV by International Agency for Research on CancerIARC

90% cervical cancer with HPV infection

HPVHigh risk HPVHR-HPVoncogenic HPVHPV 16,18,31,33,35,39,45, 51,52,56,58,59,68,73,82HSIL, Cxca

Low risk HPVLR-HPVnon-carcinogenic HPV HPV 6,11,42,43,44,54,61,70,72,81LSIL

PrecursorsCIN: Cervical Intraepithielial NeoplasmCIN Imild dysplasia1/3CIN IImoderate dysplasia1/3-2/3 CIN IIIsevere dysplasia , 3/3

CIS : carcinoma in situ

Precursors ---CINs

Cervical cancer Histological TypesSquamous carcinoma 80-85%Adenocaricinoma 15-20%Endometrial carcinomaClear cell carcinomaAdenosquamous 3-5%Undifferentiated carcinoma

Minimal deviation adenocarcinoma (MDA)Neuroendocrine tumor (small cell)

Spread patternTranscelomic most common

Lymphatic retroperitoneal ( pelvic and paraaortic ) LN spreading is common in advanced- stage

Hematogenous uncommon

FIGOstage

FIGO StagingI The carcinoma is strictly confined to the cervix (extension to the uterine corpus should be disregarded).IA Invasive cancer identified only microscopically. Invasion is limited to measured stromal invasion with a maximum depth of 5mmb and no wider than 7mm. (All gross lesions even with superficial invasion are Stage IB cancers.) IA1: Measured invasion of stroma 3mm in depth and 7mm width. IA2 : Measured invasion of stroma >3mm and 4cm in size.

II The carcinoma extends beyond the uterus, but has not extended onto the pelvic wall or to the lower third of vagina.IIA Involvement of up to the upper 2/3 of the vagina. No obvious parametrial involvement. IIA1: Clinically visible lesion 4cm IIA2: Clinically visible lesion >4cmIIB Obvious parametrial involvement but not onto the pelvic sidewall.

III The carcinoma has extended onto the pelvic sidewall. On rectal examination, there is no cancer-free space between the tumor and pelvic sidewall. The tumor involves the lower third of the vagina. All cases of hydronephrosis or non-functioning kidney should be included unless they are known to be due to other causes.IIIA Involvement of the lower vagina but no extension onto pelvic sidewall.IIIB Extension onto the pelvic sidewall, or hydronephrosis/non-functioning kidney.

IV The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder and/or rectum.IVA Spread to adjacent pelvic organs.IVB Spread to distant organs.

Platform of diagnosis for cervical diseasesPap smear TBS classificationTCTHPVColposcopy--biopsyLEEP

Cervical cancerSymptoms

No symptomsAbnormal pap smearLeukorrheaPostcoital bleedingPelvic pain

HistoryPhysical examinationCytology (pap smear, TCT)Biopsy (colposcopy)ConizationImagingCervical cancerDiagnosis

Principle for treat cervical cancerEvidence based medicineFIGO ( International Federation of Gynecology and Obstetrics) NCCN (National Comprehensive Cancer Network)

Individualized therapy

Cervical Cancer TreatmentPrecursor- CINsMicro-invasive cancerInvasive cancer

Treatment for CINsCIN I: follow up 36monthsCIN II: local therapy conizationCIN III: conization hysterectomy

Ia1: hysterectomyIa2: modified hysterectomyIa with positive margin (Ia or CIS): radical hysterectomy

Treatment for micro-invasive cervical cancer

Surgical threatment Ib-IIaRadiotherapyChemotherapy Combined therapy

Treatment for invasive cervical cancer

Cervical cancerb1/a1)

1. RH+PLND+/- PALND Radical hysterectomy+ pelvic lymph node dissection para-aortic lymph node dissection;

2. RT Pelvic RT+ Brachytherapy concurrent cisplatin-containing chemotherapy

Cervical cancerb2/a2)

1. RT Pelvic RT+concurrent cisplatin-containing chemotherapy + Brachytherapy

2. RH+PLND+/- PALND Radical hysterectomy+ pelvic lymph node dissection para-aortic lymph node dissection;

3. RT+ Hysterectomy Pelvic RT+concurrent cisplatin-containing chemotherapy + Brachytherapy +adjuvant hysterectomy

Flow-chat for management IB, IIA cervical cancer) IB1, IIA14cm

RH+PLND+/-PALNDRTCCRTRH+PLND+PALNDNACT+RH+PLND +PALNDRT+CTLN positivepositive margin

RT+/- CTpoor differentiateddeep myometrial invasionLVSIAdjuvant Therapy(according to high-risk factors)

Complications of RHVesicovaginal fistulaUreterovaginal fistulaSevere bladder atomyBowel obstructionLymphocystThrombophlebtisPulmonary embolus

Post-surgical treatment(high risk factors)

poor differentiateddeep myometrial invasionLVSILN positivepositive margin (Vaginal, parametrium)

Advanced stageb)

Radiotherapy (RT)NACT + RadiotherapyConcurrent chemo-radiotherapyCombined RT and CT

Radical TrachelectomyFertility sparing Ib

Prognosis 5yr survival rate recurrent rate patients with RT (RH)Stage I: 91.5% (86.3%) 1.5%Stage IIa: 83.5% (75%)Stage IIb: 66.5% (58.9%) 5%Stage IIIa: 45% (43%) 7.5%Stage IIIb: 36% 17%Stage IV: 14%

Data from MD Anderson Hospital

Pregnant with cervical cancer20w, evaluation, Ia-Ib1 observation;>24w, 32-34w CS+RH;

Primary prevention1. Health care2. Sexual behavior 3. Dual protection4. HPV vaccines4. Cancer screening5. Treat precursors

PreventionSecondary prevention1.Early screening2. Early treatment

SurveillanceInterval H & PEvery 3-6months for 2yr;Every 6-12months fro 3-5yrCytology/yrImaging : PET, PET-CT, MRI, CTLab oratory assessmentPatient education

Take home message HPV (HR)CINsFIGO stageSurgery: Radical hysterectomy and PLNDPost-operation treatment: high risk factorsRT and CTFertility sparing trachelectomyHPV Vaccine

OB/GYN Hospital of Fudan University THANKS

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