5CIN’lerin SeyriCIN’lerin SeyriÖstör AG, Int J Gynecol Pathol,1993
6Cervical Carcinoma The average age at diagnosis is 51 years Over 95 % of the patients with early cancer of the cervix can be cured
715% of Incidence Cervical Cancer Lifetime risk 0.8% Risk of dying 0.3% female cancers4-6% Developed20-30% DevelopingIncidencePreinv /Invasive /
8ETIOLOGY and EPIDEMIOLOGY Risk factors for cervical cancer are the same as CINHPV is central to the development of cervical neoplasia (99 % of all cervical carcinomas),HPV 16 => Squamous cell carcinomaHPV 18 => AdenocarcinomaOther risk factors:Immuno suppresionInfection of HIVHistory of other sexually transmitted disseasesHigh parityOral contraceptive use,Tobacco use
10HPV and Cervical Cancer: pathogenesis Infection with high-risk HPV typesIntegration of HPV into the human genomeExpression of viral genesSynthesis and upregulation of viral oncogenes (E6,E7)Host cell immortalization and malign transformation
11Viral oncogenes and its functions E p53 degradation,increased telomerase activityE functional inhibition of pRB
12HPV infection and incidence of cervical lesions vs years
14CLINICAL STAGINGIt is important to estimate the extent of the disease not only for prognostic purposes but also for treatment planning!!
15Serviks Kanserinin Evrelemesi(FIGO2009) Evre I: Servikse sınırlı karsinom(corpus yayılımı gözardı edilir)Evre IA: yalnız mikroskobik olarak tanımlanır,gözle görülmezEvre IA1: İnvazyon derinliği ≤ 3mm, genişiği<7 mmEvre IA2: İnvazyon derinliği >3-5 mm,genişliği <7 mmEvre IB: servikse sınırlı klinik lezyon veya > evre1A preklinik lezyonEvre IB1: Lezyon ≤ 4 cmEvre IB2: Lezyon > 4 cmEvre II: Serviks dışına çıkmış,pelvik duvara ulaşmamış karsinom,2/3 üst vajen tutulumu varEvre IIA: Belirgin parametriyal tutulum yokIIA1: lezyon ≤ 4 cmIIA2:lezyon >4 cmEvre IIB: Belirgin parametriyal tutulum varEvre III: Pelvik duvara ulaşmış karsinomEvre IIIA: Pelvik duvara yayılım yok, 1/3 alt alt vajen tutulumu varEvre IIIB: Pelvik duvara yayılım var ve/veya hidronefroz veya nonfoksiyone böbrekEvre IV: Gerçek pelvis dışına ulaşmış karsinomEvre IVA: Komşu organlara yayılım(klinik veya biopsi ile kanıtlanmış olarak mesane ve rektum mukozası tutulumu var)Evre IVB: Uzak metastaz
16Staging Chemical Studies X-Ray studies (IVP, etc) Endoscopic CLINICAL (FIGO, TNM)Chemical StudiesX-Ray studies (IVP, etc)EndoscopicExamination Under General AnesthesiaLymphatic imaging interventions
17Number of Patients with respect to stages IVIAIII275740510122IIIB
18TREATMENTInvasive carcinoma of the cervix spreads primarily by direct extension and lymphatic dissemination.The therapy accomplished by either radical hysterectomy and pelvic lymphadenectomy, radiation with concominant chemotherapy or a combination thereof.
20Strategies in Treatment of Early Cervical Cancer Primary lesionPossible metastatic sites
21TREATMENT of Early Stage Disease (Stage IA2 to IIA) Radical hysterectomy and pelvic lymphadectomyRadical Hysterectomy with pelvic lymphadenectomy is the surgical procedure for invasive cancer limited to the cervix (Stage I and II)Stage IA1 => Type I HysterectomyStage IA2 => Type II (Modified radical hysterectomy)Stage IB-IIA => Type III HysterectomyPrimary radiation with concominant chemotherapy
22TREATMENT of Early Stage Disease (Stage IA2 to IIA) Adjuvant Post Operative RadiationIndicationsPositive lymph nodesPositive or close resection marginsMicroscopic parametrial involvement
23SPECIAL SITUATIONS STAGE IA DISEASE RADICAL TRACHELECTOMY For a young woman desiring to maintain fertility, conization may be acceptable if:Depth of invasion of 3 mm or lessConization margins are negativeThere is no evidence of lymphovascular space invasionRADICAL TRACHELECTOMY
24TREATMENT of Locally Advanced Disease (Stage IIB to IVA) Primary radiationwith concominant chemotherapyStage 3b
25TREATMENT of Disseminated Primary Disease (Stage IVB) Chemotherapy
26When the lymphatics are involved, tumor cells are carried to the regional pelvic lymph nodes. (parametrial, hypogastric, obturator, external iliac and sacral)Ovarian involvement is rare, the liver and lungs are the most common sites of blood-borne metastasis rarely involves the brain, bones, bowels, adrenal glands, spleen or pancreas
28Death can occur fromuremia,pulmoner embolism orhemorrhage from direct extension of tumor into blood vesselPyelonephritis, vesicovaginal and rectovaginal fistules are possible and may cause life-threatening sepsis
29Prevention of Cervical Cancer CounsellingBarrier contraceptivesMonogamyScreeningVaccineDiet
30PREVENTIONRisk factors must be recognized and screening, treatment, intervention and patient education must be modified respectively.Universal cytologic screening of all post pubertal women must be continuedGardasil a quadrivalent vaccine against HPV16/18/6/11 received FDA approval in the USA for use in girls and women 9 – 26 years old.