Cervical cancer Fuat Demirkıran, MD Istanbul University, Cerrahpaşa School Of Medicine, OB&GYN Department, Gyn Oncology
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.
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
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.
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
Transmision: genital skin to skin contact Cofactors Hormonal Influances Parity Other STIs Smoking Nutritions Host genetics Viral genetics Transient HPV infection Persistent infection with oncogenic HPV types LSIL/CIN I HSIL/CIN II - III Invasive cervical cancer from Franco and Harper 2005, Trottier H ,Franco EL, Vaccine 2006
Briefly ·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 IICIN III Cancer ·Squamous carcinoma of the cervix arises at the active SCJ from pre-existing dysplastic lesion.
Normal % 57 Regress CIN I % 43 Regress % 31 CIN II CIN III % 30 % 35 % 56 CIN I CIN II CIN III % 22 % 11 % 14 %0.3 Cancer CIN II - III Cancer CIN III-Kanser n: 4504 Ostor AG, 1993 Michell MF., 1996 Wright TC., 2002
HHISTOLOGIC 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
SYMPTOMS 1.20% of patients are asymtomatic . . vaginal bleeding.......postcoital, irregular men, postmenopausal 3 . vaginal discharge 4 .. pain
Diagnosis Symptomatic biopsy Asymptomatic abnormal cytology Colposcopic examination Biopsy
Vaginal Cytology a. Conventional Pap test b. Liquid-based cytology
Biopsy techniques for cervical evaluation Punch biyopsy Leep excision Conization
Conization end-point diagnostic work-up for cervical pathology
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.
Pathologic Prognostic Factors Related to Cervical Cancer Pelvic lymphatic status Tumor size Deep of invasion LVSI Close surgical margin Positive surgical margin
The Relationship of Pelvic Lymph Node Metastasis and 5-year Survival Node negative Node positive n Survival n 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%
The Main Prognostic Factors in Cervical Cancer n 5-year survival p 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 Kristensen et al, Gynecol Oncol 1999
The Influence of LVSI on Pelvic Lymph Node Metastasis and Survival in Early Stage Cervical Carcinoma LVSI negative LVSI positive n survival pel nod + n survival pel nod + Crissman 1985 94 97% 8% 30 64% 17% Delgado 1990 360 90% 8% 276 78% 25% Roman 1998 32 - 0% 73 - 32%
Molacular Prognostic Factors of Cervical Cancer DNA cytometry COX-2 expression nm23 expression Tymidine kinase Beta-catanin Id-1 protein Matrix metaloproteinases and others
The principles of treatment for cervical cancer composed of.. Sites of spread Primary tumor Surgery Radiotherapy
Surgery Radiotherapy Stage Ia-Ib1- II a Stage Ib2-III-IV
The results of surgery and radiotherapy are almost equalTreatment of cervical cancer depends on patients age, sexual status, fertilty statusIf the patient is young and sexualy active , surgery is the best choise
Surgical TreatmentStage Ia1Conization is adequate for women who desire fertility if there is no lymphovascular space invasionorType I hysterectomy for women who not desire fertility
Surgical TreatmentStage Ia2Type II or III hysterectomy with pelvic lymphadenectomyStage Ib1- Stage IIa- Type III hysterectomy with pelvic lymphadenectomy
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
After surgery if surgical margin is positive or lymph node is positive, postoperative RT is mandatory
Primer radio-chemotherapy is the best choise For stage Ib2 and > IIb diseases
Fertility sparing surgery for cervical cancer 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