cervical cancer dr khalid h. wali sait (frcsc) associate professor of gynecological oncology king...
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Cervical Cancer
DR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia
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Cancer in Women World Wide
Breast Colo-rectal Cervix and Uterus Lung Leukemia-Lymphoma Ovary
Saudi Breast Thyroid Leukemia–Lymphoma Colo-rectal Ovary Liver Cervix Uterus
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Female Genital Tract Malignancy
World Wide Uterus Cervix Ovary Vulva Vagina F.Tube
Saudi Ovary Cervix Uterus Vulva Vagina F.Tube
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Pathogenesis HPV are etiological agent for cancer cervix HPV DNA can be found in 99.7 % of all
cervical carcinoma Type 16, 18, 45 and 31 most frequent.
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HPV >100 types identified2
~30–40 anogenital2,3
~15–20 oncogenic*,2,3 types, including 16, 18, 31, 33, 35, 39, 45, 51, 52, 584
HPV 16 (54%) and HPV 18 (13%) accounted for the majority of worldwide cervical cancers.5
Nononcogenic** types include: 6, 11, 40, 42, 43, 44, 544
HPV 6 and 11 are most often associated with external genital warts.3
1. Howley PM. In: Fields Virology. Philadelphia, Pa: Lippincott-Raven; 1996:2045–2076. 2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 3. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 4. Muñoz N, Bosch FX, de Sanjosé S, et al. N Engl J Med. 2003;348:518–527. 5. Clifford GM, Smith JS, Aguado T, Franceschi S. Br J Cancer. 2003:89;101–105.
Nonenveloped double-stranded DNA virus1
*High risk; **low risk
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Infectious Virus Particle of HPV1,2
Capsid proteins:Capsid proteins:L1L1L2L2
Viral DNAViral DNA
Viral exterior Viral interior
1. Baker TS, et al. Biophys J. 1991;60:1445–1456. 2. Chen XS, et al. Mol Cell. 2000;5:557–567.
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Pathogenesis P53
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Spectrum of Changes in Cervical Squamous Epithelium Caused by HPV Infection1
Normal Normal CervixCervix
HPV Infection /HPV Infection /CIN* 1CIN* 1
CIN 2 / CIN 3 /CIN 2 / CIN 3 /Cervical CancerCervical Cancer
*CIN = cervical intraepithelial neoplasia
1. Adapted from Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564. Copyright © 2003 Massachusetts Medical Society. All rights reserved. Adapted with permission.
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0–1 Year 0–5 Years 1–20 Years
Invasive Cervical Cancer
Cleared HPV Infection
1. Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.
CIN 1
InitialHPV
Infection
ContinuingInfection
CIN 2/3
Natural History of HPV Infection and Potential Progression to Cervical Cancer1
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HPV Clearance In women 15-25 years of age ~80% of
HPV infections are transient Gradual development of cell-mediated
immune response presumed mechanism In a study of 608 college women, 443
infected, 70% of new infections cleared within 1 year and 91% within 2 years Mean duration of infection - 8 months HPV 16 and 18 infections persist longer
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Cervical Cancer Prevention
Education About early symptom of cancer cervix
Avoid Risk Factors Screening and Vaccine
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Risk Co Factor: HIV HPV 16,18 SMOKING MULTIPPLE SEXUAL PARTNER ? BCP
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Cancer Cervix Has an easily identified pre-
invasive disease and be diagnosed and treated before become an invasive disease
Screening Test
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THIN PREP Liquid based cytology
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Q7
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Recommendations of ACS(2004)
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False negative ( 30%)
GOOD SCREENING ?
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Ideal (not essential) Patient’s Conditions For Screening
No vagina douching for 48 hours Avoided use of contraceptive
creams or jellies for 48 hours No intercourse for 24 hours Not recommended during
menstruation, mid cycle smear is optimum
Patient should be required to provide her LMP
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Changes in Terminology
HPVMild Dysplasia
HPVCIN I
L SIL
Moderate Dysplasia
CIN II H SIL
Severe DysplasiaCarcinoma insitu
CIN III H SIL
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Management Of Pap Smear Result
Pap smear is simply a lab test it is the responsibility of the physician to interpret the result in the context of a given patient and her particular circumstances
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Objective Of Colposcopy
Exclude invasive disease Select the most appropriate area
for biopsy
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•Original squamocolumnar junction
•Present squamocolumnar junction
•Transformation zone
•Endocervical canal
IS COLPOSCOPY SATISFACTORY ?
Detailed Colposcopic Exam.
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a grape-like or "sea-anemone"
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RCT
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Cancer of the CervixClinical presentation
Abnormal vaginal bleeding Postmenopausal Vaginal bleeding Vaginal discharge Pain Asymptomatic
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Invasive Disease
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Cancer of the Cervix Histological types Squamous cell ca Adenocarcinoma Other
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Cancer of the CervixMode of spread
Direct Lymphatic Hematogenous
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Cancer of the Cervix Investigations EUA Complete blood count Liver function test Renal function tests CXR/IVP or CT Cystoscopy Sigmoidoscopy
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Cancer of the CervixFIGO Staging ( clinical )
I - Tumour confined to the cervix II- Upper 2/3 vagina / parametrium. III- Lower 1/3 vagina / pelvic side
wall or hydronephrosis IV- Adjacent organ / Distant
metastasis
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Cancer of CervixPrognostic Factors
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Cancer of the Cervix Treatment of patients
Radical Hysterectomy and lymphadnectomy Radiation Therapy
and chemotherapy
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Pelvic RadiationEBR and Brachytherapy
Chemotherapy
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What is: Radiotherapy
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How Radiotherapy works ?
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Follow up
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RECURRENT CERVICAL CANCER Treatment depends on:
Site of recurrence Mode of primary therapy
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Cancer of the Cervixstage/survival
Stage 5 years survival %
Ia1 100 Ia2 95 Ib1 85 Ib2 70 II 50-60 III-IV 10-40
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Prophylactic Vaccine Virus – neutralization antibodies to
prevent infection Generate antibodies in genital
tract epithelium directed against the L1 and L2 capsid proteins
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Commercial HPV Vaccines
GSK vaccine (Harper 2004) 16/18(100% efficacy)
Merck vaccine (villa 2005) 6/11/16/18 ( 88% efficacy (RCT PLACEBO)
0,1,6 months 16-23 y old
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Gardasil: Quadrivalent HPV Vaccine 0.5 ml IM, day 0, month 2, and month 6 COST ~$130 each vaccine dose Storage: 2-8oC, should not be frozen, protect from light.
*NEED TO PRESERVE THE “COLD CHAIN”* Contraindications: hypersensitivity to the active
substances or components Precautions:
May not be effective Not for use in active warts, cervical cancer, CIN VIN, VAIN Does not provide protection against none vaccine HPV
types Not recommended for use in pregnancy, Category B
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Who? Women 9-26 Do not need to have pap smear
before vaccination Testing for HPV is not
recommended prior to vaccination Sexually active women can be
vaccinated, may be less effective in women who have been previously exposed to HPV
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Cervical Cancer
DR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia