1. Cervical cancer Fuat Demirkıran, MD Istanbul University, Cerrahpaşa School Of Medicine, OB&GYN Department, Gyn Oncology

3. Incidence of Cervical Cancer (GloboCan/IARC 2000) – in per 100 000 women

4. Cervical cancer is a preventable cancer because it has a long preinvasive state. The incidence of CC is decreasing and it is being diagnosed earlier during last 50 years..... due to cervical cytology screening programs Mean age for cervical cancer is 50 years and it peaks at 35-40 years and 60-64 years.

5. Risk factors for development of CC sexuel intercourse at an early age multiple sexuel partners young age at first pregnancy cigarette smoking HSV infection HPV infection

6. HPV and Cervical Cancer International collection of cervical tumor specimens showed that HPV DNA is present in 99.7% of cases. Relative risks for the association between HPV and cervical cancer are in 50-150 range.

7. The most important HPV types related to Cervical Preinvazive and invazive lesion Schiffman, J Nat Cancer Inst, 85:958, 1993 and Liaw, J Nat Cancer Inst, 91:954, 1999

8. Transmision: genital skin to skin contact Transient HPV infection Persistent infection with oncogenic HPV types LSIL/CIN IHSIL/CIN II - III Invasive cervical cancer Cofactors Hormonal Influances Parity Other STIs Smoking Nutritions Host genetics Viral genetics from Franco and Harper 2005, Trottier H,Franco EL, Vaccine 2006

9.  HPV with the assistance of some cofactors can result in the development of CC. All of the invasive squamous CC develope at the end of progressive pathologic events. NNormal epithel CIN I CIN II CIN III Cancer · Squamous carcinoma of the cervix arises at the active SCJ from pre-existing dysplastic lesion. Briefly

10. CIN I % 57 % 11 %0.3 Normal CIN II - III Cancer n: 4504 Ostor AG, 1993 CIN IICIN III % 43 Regress % 22 CIN III-Kanser % 14 Cancer % 30 % 35 % 56 CIN II CIN III Michell MF., 1996 Wright TC., 2002 Regress % 31 CIN I

11. H H ISTOLOGIC TYPES OF CC 1. squamous cell carcinoma....most common type 2. adenocarcinoma (AC)....in recent years, an increasing number of AC affecting young women....AC are populated by musinous endocervical cells, endometroid cells, clear cells....10 % -15 of CC....considered that AC is poorly prognostic tumor compared with squamous cell carcinoma 3. minimal deviation adenocarcinoma(adenoma malignum).....extremely well-diferentiated form of AC 4. villoglandular papillary adenocarcinoma 5. adenosquamous carcinom 6. glassy cell carcinoma

12. S YMPTOMS 1. 20% of patients are asymtomatic.. vaginal bleeding.......postcoital, irregular men, postmenopausal 3. vaginal discharge 4.. pain

13. Asymptomatic abnormal cytology Symptomatic biopsy Diagnosis Colposcopic examination Biopsy

14. a. Conventional Pap test b. Liquid-based cytology Vaginal Cytology

15. Colposcopy

16. Punch biyopsy Leep excision Conization Biopsy techniques for cervical evaluation

17. LEEP Excision - Conization

18. Conization end-point diagnostic work-up for cervical pathology

19. PATTERNS OF SPREADING 1. Direct invasion into the cervical stroma, vagina, uterine corpus and parametrium 2. Lymphatic metastases 3. Hematologic metastases 4. Intraperitoneal metastases Predominanat spread patterns : direct extension and lymphatic dissemination Malignant cells spread by way of paracervival lymphatic cannels into the obturator, internal iliac, external iliac, common iliac and para-aortic lymph nodes group.

20. 2009

21. Pathologic Prognostic Factors Related to Cervical Cancer Pelvic lymphatic status Tumor size Deep of invasion LVSI Close surgical margin Positive surgical margin

22. The Relationship of Pelvic Lymph Node Metastasis and 5-year Survival Monoghan 1990 392 92% 102 50% Delgado 1990 545 86% 100 83% Kamura 1992 281 91% 64 63% Lai 1999 610 87% 217 68% n Survival n Survival Node negative Node positive

23. The Main Prognostic Factors in Cervical Cancer Tumor size (cm) < 2 58 %94 <0.00001 2-3.9 48 %79 >4 10 % 47 Depth of invasion(mm) <10 75 %94 <0.00001 11-15 27 %73 16-20 14 %57 >20 9 %33 n 5-year survival p Kristensen et al, Gynecol Oncol 1999

24. The Influence of LVSI on Pelvic Lymph Node Metastasis and Survival in Early Stage Cervical Carcinoma Crissman 1985 94 97% 8% 30 64% 17% Delgado 1990 360 90% 8% 276 78% 25% Roman 1998 32 - 0% 73 - 32% n survival pel nod + n survival pel nod + LVSI negative LVSI positive

25. Molacular Prognostic Factors of Cervical Cancer DNA cytometry COX-2 expression nm23 expression Tymidine kinase Beta-catanin Id-1 protein Matrix metaloproteinases and others

26. Treatment of Cervical Cancer

27. The principles of treatment for cervical cancer composed of.. Sites of spread Primary tumor Surgery Radiotherapy

28. Surgery Radiotherapy Stage Ia-Ib1- II a Stage Ib2-III-IV

29. The results of surgery and radiotherapy are almost equal Treatment of cervical cancer depends on patients age, sexual status, fertilty status If the patient is young and sexualy active, surgery is the best choise

30. Surgical Treatment Stage Ia1 Conization is adequate for women who desire fertility if there is no lymphovascular space invasion or Type I hysterectomy for women who not desire fertility

31. Surgical Treatment Stage Ia2 Type II or III hysterectomy with pelvic lymphadenectomy Stage Ib1- Stage IIa- Type III hysterectomy with pelvic lymphadenectomy

33. Radikal histerektomi and Lymphadenektomi

34. Radical Hysterectomy(Type II-III) for stage Ia2, Ib and IIa immediate therapy staging and tailoring of therapy conservation of the ovaries conservation of sexual function The results of surgery and radiotherapy are almost equal

35. After surgery if surgical margin is positive or lymph node is positive, postoperative RT is mandatory

36. Primer radio-chemotherapy is the best choise For stage Ib2 and > IIb diseases

37. Results of Trachelectomy n:130 Ia1 17 Ia2 36 Ib1 74 IIa 3 Squamous 93 Adeno ca 37 < 2 cm 110 > 2 cm 10 Intraop complication %9 Postop “ %10 Positive node %2.4 Mean follow-up 27 ay Tumor reccurrence %3.1 Pregnancy 54 Dargent 2000, Plante 1999, Covens 1999, Shepherd 1998 Fertility sparing surgery for cervical cancer