Cervical Cancer Xin LU OB/GYN Hospital Fudan University

1. Cervical CancerXin LU OB/GYN Hospital Fudan University

2. Contents • General information • CINs • Spread pattern • FIGO staging • Clinical signs • Diagnosis and differential diagnosis • Principle for treatment • Prevention • Surveillance

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

4. Female Reproductive Anatomy

5. 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.

6. Cxca Progression HPV infection CINs Carcinoma in situ ≈10-15yr Cervical cancer

7. EtiologyHigh-risk factors • HR-HPV • Use of oral contraceptives • Smoking • Multiple sexual partners • History of herpes infection • History of STD

8. Human Papillomavirus , HPV人乳头瘤状病毒 • 1972：Harald zur HausenZur Hausen • 1995：High-risk HPV by International Agency for Research on Cancer，IARC • 90% cervical cancer with HPV infection

9. 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

10. 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

11. Precursors ---CINs

12. 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%

13. Spread pattern • Transcelomic • most common • Lymphatic • retroperitoneal ( pelvic and paraaortic ) LN spreading is common in advanced- stage • Hematogenous • uncommon

14. FIGO stage

15. 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.

16. Platform of diagnosis for cervical diseases • Pap smear TBS classification • TCT • HPV • Colposcopy--biopsy • LEEP

17. Cervical cancerSymptoms • No symptoms • Abnormal pap smear • Leukorrhea • Postcoital bleeding • Pelvic pain

18. Cervical cancerDiagnosis • History • Physical examination • Cytology (pap smear, TCT) • Biopsy (colposcopy) • Conization • Imaging

19. Principle for treat cervical cancer • Evidence based medicine • FIGO ( International Federation of Gynecology and Obstetrics) • NCCN (National Comprehensive Cancer Network) • Individualized therapy；

20. Cervical Cancer Treatment • Precursor- CINs • Micro-invasive cancer • Invasive cancer

21. Treatment for CINs • CIN I: follow up 3—6months • CIN II: • local therapy • conization • CIN III: • conization • hysterectomy

22. Treatment formicro-invasive cervical cancer • Ia1: hysterectomy • Ia2: modified hysterectomy • Ia with positive margin (Ia or CIS): radical hysterectomy

23. Treatment for invasive cervical cancer • Surgical threatment Ib-IIa • Radiotherapy • Chemotherapy • Combined therapy

24. 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

25. Cervical cancer（Ⅰb2/Ⅱa2) 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

26. Flow-chat for management（ IB, IIA cervical cancer) IB1, IIA1 <4cm IB2, IIA2 >4cm RH+PLND+/-PALND RT CCRT RH+PLND+PALND NACT+RH+PLND +PALND Adjuvant Therapy (according to high-risk factors) RT+CT LN positive positive margin RT+/- CT poor differentiated deep myometrial invasion LVSI

27. Complications of RH • Vesicovaginal fistula • Ureterovaginal fistula • Severe bladder atomy • Bowel obstruction • Lymphocyst • Thrombophlebtis • Pulmonary embolus

28. Post-surgical treatment(high risk factors) poor differentiated deep myometrial invasion LVSI LN positive positive margin (Vaginal, parametrium)

29. Advanced stage（Ⅱb，Ⅲ，Ⅳ) • Radiotherapy (RT) • NACT + Radiotherapy • Concurrent chemo-radiotherapy； • Combined RT and CT

30. Radical Trachelectomy • Fertility sparing • Ib <4cm • Evaluation of infertility factor • Procedure of trachelectomy • Vaginal • Laparoscopic • Abdominal • Complications • Outcome

31. Prognosis 5yr survival raterecurrent 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

32. Pregnant with cervical cancer • <20w, operation; • >20w, evaluation, Ia-Ib1 observation; • >24w, 32-34w CS+RH;

33. 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

34. 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

35. 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

36. THANKS OB/GYN Hospital of Fudan University