Cervical Cancer

DR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia

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

Female Genital Tract Malignancy

World Wide Uterus Cervix Ovary Vulva Vagina F.Tube

Saudi Ovary Cervix Uterus Vulva Vagina F.Tube

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.

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

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.

Pathogenesis P53

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.

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

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

Cervical Cancer Prevention

Education About early symptom of cancer cervix

Avoid Risk Factors Screening and Vaccine

Risk Co Factor: HIV HPV 16,18 SMOKING MULTIPPLE SEXUAL PARTNER ? BCP

Cancer Cervix Has an easily identified pre-

invasive disease and be diagnosed and treated before become an invasive disease

Screening Test

THIN PREP Liquid based cytology

Q7

Recommendations of ACS(2004)

False negative ( 30%)

GOOD SCREENING ?

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

Changes in Terminology

HPVMild Dysplasia

HPVCIN I

L SIL

Moderate Dysplasia

CIN II H SIL

Severe DysplasiaCarcinoma insitu

CIN III H SIL

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

Objective Of Colposcopy

Exclude invasive disease Select the most appropriate area

for biopsy

•Original squamocolumnar junction

•Present squamocolumnar junction

•Transformation zone

•Endocervical canal

IS COLPOSCOPY SATISFACTORY ?

Detailed Colposcopic Exam.

a grape-like or "sea-anemone"

RCT

Cancer of the CervixClinical presentation

Abnormal vaginal bleeding Postmenopausal Vaginal bleeding Vaginal discharge Pain Asymptomatic

Invasive Disease

Cancer of the Cervix Histological types Squamous cell ca Adenocarcinoma Other

Cancer of the CervixMode of spread

Direct Lymphatic Hematogenous

Cancer of the Cervix Investigations EUA Complete blood count Liver function test Renal function tests CXR/IVP or CT Cystoscopy Sigmoidoscopy

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

Cancer of CervixPrognostic Factors

Cancer of the Cervix Treatment of patients

Radical Hysterectomy and lymphadnectomy Radiation Therapy

and chemotherapy

Pelvic RadiationEBR and Brachytherapy

Chemotherapy

What is: Radiotherapy

How Radiotherapy works ?

Follow up

RECURRENT CERVICAL CANCER Treatment depends on:

Site of recurrence Mode of primary therapy

Cancer of the Cervixstage/survival

Stage 5 years survival %

Ia1 100 Ia2 95 Ib1 85 Ib2 70 II 50-60 III-IV 10-40

Prophylactic Vaccine Virus – neutralization antibodies to

prevent infection Generate antibodies in genital

tract epithelium directed against the L1 and L2 capsid proteins

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

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

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

Cervical Cancer

DR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia