Cancer screening

Population based No sign and symptom To identify asymptomatic individual with risk acquiring cancer Need further procedure

Criteria of effective screening

The cancer is major health problem Treatable in early stage The test is acceptable Not expensive Cost effective No pain/harm Specific and sensitive Reduce mortality

Possible adverse effect

Discomfort from the test Anxiety Potential side effect False positive test Risk of over diagnosis (pseudo disease)

Cervical Cancer Prevention

Primary prevention : prevention of HPV infection Secondary prevention : detection and treatment pre cancerous state Tertiary prevention : adequate treatment

Primary Prevention

Education Vaccine

Secondary Prevention

Screening Management pre cancer lesion

Types of Cervical Cancer Screening

Cytology Visual inspection HPV testing Others

Screening interval

Depend on government policy Varies from country to country Screening interval 2-3 year as effective as yearly screening Target aged depend on government program High risk group : yearly screening

Cytology Screening

First proposed by Dr. George Papanicolaou in 1940s Ayre in 1947 introduce wooden spatula Significantly reduced incidence and mortality Paps test not very sensitive Sensitivity 40% - 80% False negative 8 50% Sample quality very important Conventional and liquid based test

Squamous-collumnar junction

endocervix

ectocervix

Squamous columnar junction

endocervix

Nabothian cyst

ectocervix New squamous columnar junction

Transformation Zone (TZ)

NSCJ TZ

Obtaining Optimal Smear

No Douching and vaginal washing Last intercourse > 48 hours Not menses Before bimanual examination Spatula rotated 360o Spread well on slide Immediate fixation

Normal smear

Cervical dysplasia

Terminology of Cytologic Report

Papanicolaou : class 1 5 WHO (1973) : mild, moderate, severe dysplasia Bethesda I (1988), revised 1991: CIN 1,2,3 with undetermined significant 2001 revised : LSIL (CIN 1) and HSIL (CIN 2,3)

TERMINOLOGY
Class I Normal Class II Inflam Class III Mild Mod Class IV Class V Cancer

Sev
CIS CIN III

Dysplasia CIN I CIN II

Normal

Atypia Benign Cellular Changes

Koilocytosis AS CUS

Cancer

WNL

LGSIL

HGSIL

HGSIL

Carcinoma

NEGATIF

AS CUS

LGSIL

HGSIL

HGSIL

Carcinoma

Visual Inspection

Direct inspection : VIA or VILI Treatment at same setting : see and treat Country with low resources VIA : white epithelium VILI : remain unstained Positive predictive value : 10% Negative predictive value : 99% Treat with cryotherapy

VISUAL INSPECTION ACETIC ACID

Aided Visual Inspection of Cervix, or Acetic Acid Test

HPV Testing

All cervical cancer correlated with HPV Equivocal cytologic : ASCUS Follow up after CIN 2-3 treatment Reduced over treatment for (+) test As primary screening Genotype evaluation

HPV Testing
Hybrid Capture 2 ( HC2) Polymerase Chain Reaction (PCR)

In Situ Hybridization (ISH)

Human Papilloma Virus and

Vaccination

HPV

Harald zur Hausen (German) : link between HPV and cervical cancer Member of family Papavoviridae Double stand DNA virus Encodes 8 proteins Six early : E1, E2, E4, E5, E6, E7 Two late : L1 and L2

HPV

E6 and E7 are oncoprotein Epitheliotropic : mucous and skin No viralemia Evade from immune system More than 150 genotype Infect anogenetal : 40 type High risk and low risk

HPV transmission

Sexually transmitted disease Skin to genital skin contact Condom not effective Non sexual routes

Secondary Prevention

Limitation of secondary prevention:

Not prevent HPV infection Rapid progression lesion : not detected Missing endocervical lesion Limited sensitivity and specificity High labor

HPV Vaccine

Almost 100% cervical cancer contain HPV DNA Primary prevention :

Health promotion Change sexual behavior Avoiding co-factors Vaccination

HPV Vaccine

Discovered by Ian Frazer and Jian Zhou Synthesize particle mimic the virus L1 capsid protein

Virus like particle (VLP) Without viral genome Non infectious But generated specific antibodies

HPV Vaccine

Available in market : two types Quadrivalent : HPV 16, 18, 6, 11 Bivalent : HPV 16 and 18 Antibodies titer : peak at 7 month Relative stable : no booster Transudation or direct exudation to the cervix

Mekanisme Perlindungan Vaksin

Infesi baru dicegah Infeksi dicegah menyebar ke tempat lain

Mengurangi viral load setelah dilepaskan

Adapted from Schwarz TF & Leo O. Gynecol Oncol 2008; 110: S1

HPV Vaccine
Weakness Oncogenic type : only 16,18 Not covered other high risk type Less cross protection Storage at cold temperature Expensive

Administration Guidelines

Most effective before infection IM injection in 3 doses Months : 0, 1 or 2 and 6 Permitted with:

Not recommended in pregnancy observed 15 after vaccination A part of prevention strategy Not replace cancer screening

Other vaccine Immunocompromised Mild acute illness Lactating women

Management Pre Invasive Disease

Introduction Screening not diagnostic procedure Treatment based on diagnostic (+) screening proceed with diagnostic Diagnostic based on histology Pre invasive lesion called CIN CIN : cervical intra epithelial neoplasm CIN 1 : mild dysplasia CIN 2 : moderate dysplasia CIN 3 : severe dysplasia

Abnormal Pap smear

Unsatisfactory : repeat 3 months Severe infection : treat Atrophic smear : repeat after estrogen ASCUS : colposcopy LSIL / HSIL : colposcopy

Colposcopy

Introduced by Hinselman in 1925 Lower power and stereoscopy microscope Direct inspection White epithelium, mosaic, puctata, abnormal vascular pattern Biopsy at abnormal area Targeting biopsy Histological diagnosed

Management CIN

CIN 1

Poor compliance Persistent > 12 months HPV (+)

Mandatory Local ablative Excisional

CIN 2 and 3

Local Ablative Treatment

Cryotherapy

Freezing at minus 200C Cell destroyed (cryonecrosis) N2O or CO2 gases

Electro diathermy Laser

More precise Less lateral thermal injuries expensive

No tissue specimen

10 1 2

5 4 6 8

1. Probe 2. Trigger 3. Handle grip (fiberglass) 4. Yoke 5. Instrument inlet of gas from cylinder 6. Tightening knob 7. Pressure gauge showing cylinder pressure 8. Silencer (outlet) 9. Gas-conveying tube 10. Probe tip

Excisional treatment

LEEP / LLETZ

LEEP : loop electrosurgical procedure LLETZ : large loop excision of the transformation zone

Laser conization Cole knife cone biopsy Trachelectomy Hysterectomy

Equipment

Suction evacuation system Electrosurgical unit Loops, ball electrode

Procedure