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Cervical Cancer Xin LU OB/GYN Hospital Fudan University Contents General information CINs Spread pattern FIGO staging Clinical signs Diagnosis and differential diagnosis Principle for treatment Prevention Surveillance Key words Cervical 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 子宫颈癌 World report: Account for 1/3 female malignancies New cases: 529 800 Death: 275 100 85% 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 Etiology High-risk factors HR-HPV Use of oral contraceptives Smoking Multiple sexual partners History of herpes infection History of STD Human Papillomavirus , HPV 人乳头瘤状病毒 1972:Harald zur Hausen Zur Hausen 1995:High-risk HPV by International Agency for Research on Cancer,IARC 90% cervical cancer with HPV infection HPV High risk HPV(HR-HPV) oncogenic HPV HPV 16,18,31,33,35,39,45, 51,52,56,58,59,68,73,82 HSIL, Cxca Low risk HPV(LR-HPV) non-carcinogenic HPV HPV 6,11,42,43,44,54,61,70,72,81 LSIL Precursors CIN: Cervical Intraepithielial Neoplasm CIN I:mild dysplasia,1/3 CIN II:moderate dysplasia,1/3-2/3 CIN III:severe dysplasia , 3/3 CIS : carcinoma in situ Precursors ---CINs Cervical cancer Histological Types Squamous carcinoma 80-85% Adenocaricinoma 15-20% Endometrial carcinoma Clear cell carcinoma Adenosquamous 3-5% Undifferentiated carcinoma Minimal deviation adenocarcinoma (MDA) Neuroendocrine tumor (small cell) <5% Spread pattern Transcelomic most common Lymphatic retroperitoneal ( pelvic and paraaortic ) LN spreading is common in advanced- stage Hematogenous uncommon FIGO stage FIGO Staging I 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 <5mm in depth and ≤7mm width. IB Clinical lesions confined to the cervix, or preclinical lesions greater than stage IA. IB1: Clinical lesions no greater than 4cm in size. IB2: Clinical lesions >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 >4cm IIB 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 diseases Pap smear TBS classification TCT HPV Colposcopy--biopsy LEEP Cervical cancer Symptoms No symptoms Abnormal pap smear Leukorrhea Postcoital bleeding Pelvic pain Cervical cancer Diagnosis History Physical examination Cytology (pap smear, TCT) Biopsy (colposcopy) Conization Imaging Principle for treat cervical cancer Evidence based medicine FIGO ( International Federation of Gynecology and Obstetrics) NCCN (National Comprehensive Cancer Network) Individualized therapy; Cervical Cancer Treatment Precursor- CINs Micro-invasive cancer Invasive cancer Treatment for CINs CIN I: follow up 3—6months CIN II: local therapy conization CIN III: conization hysterectomy Treatment for micro-invasive cervical cancer Ia1: hysterectomy Ia2: modified hysterectomy Ia with positive margin (Ia or CIS): radical hysterectomy Treatment for invasive cervical cancer Surgical threatment Ib-IIa Radiotherapy Chemotherapy Combined therapy Cervical cancer(Ⅰb1/Ⅱa1) 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 cancer(Ⅰb2/Ⅱa2) 1. RT Pelvic RT+concurrent cisplatin-containing chemotherapy + Brachytherapy 2. RH+PLND+/- PALND Radical hysterectomy+ pelvic lymph node dissection ±paraaortic lymph node dissection; 3. RT+ Hysterectomy Pelvic RT+concurrent cisplatin-containing chemotherapy + Brachytherapy +adjuvant hysterectomy Flow-chat for management ( IB, IIA cervical cancer) IB2, IIA2 >4cm IB1, IIA1 <4cm CCRT RH+PLND+PALND NACT+RH+PLND +PALND RH+PLND+/-PALND RT Adjuvant Therapy (according to high-risk factors) RT+CT LN positive positive margin RT+/- CT poor differentiated deep myometrial invasion LVSI Complications of RH Vesicovaginal fistula Ureterovaginal fistula Severe bladder atomy Bowel obstruction Lymphocyst Thrombophlebtis Pulmonary embolus Post-surgical treatment (high risk factors) poor differentiated deep myometrial invasion LVSI LN positive positive margin (Vaginal, parametrium) Advanced stage(Ⅱb,Ⅲ,Ⅳ) Radiotherapy (RT) NACT + Radiotherapy Concurrent chemo-radiotherapy; Combined RT and CT Radical Trachelectomy Fertility sparing Ib <4cm Evaluation of infertility factor Procedure of trachelectomy Vaginal Laparoscopic Abdominal Complications Outcome Prognosis 5yr survival rate patients with RT (RH) Stage I: 91.5% (86.3%) Stage IIa: 83.5% (75%) Stage IIb: 66.5% (58.9%) Stage IIIa: 45% (43%) Stage IIIb: 36% Stage IV: 14% recurrent rate Data from MD Anderson Hospital 1.5% 5% 7.5% 17% Pregnant with cervical cancer <20w, operation; >20w, evaluation, Ia-Ib1 observation; >24w, 32-34w CS+RH; Prevention Primary prevention 1. Health care 2. Sexual behavior 3. Dual protection 4. HPV vaccines 4. Cancer screening 5. Treat precursors Secondary prevention 1.Early screening 2. Early treatment Surveillance Interval H & P Every 3-6months for 2yr; Every 6-12months fro 3-5yr Cytology/yr Imaging : PET, PET-CT, MRI, CT Lab oratory assessment Patient education Take home message HPV (HR) CINs FIGO stage Surgery: Radical hysterectomy and PLND Post-operation treatment: high risk factors RT and CT Fertility sparing trachelectomy HPV Vaccine THANKS OB/GYN Hospital of Fudan University