PENELITIAN EPIDEMIOLOGI

UNTUK
PROGRAM PENCEGAHAN
KANKER SERVIKS
RATNA DJUWITA
DEPARTEMEN EPIDEMIOLOGI
FAKULTAS KESEHATAN MASYARAKAT
UNIVERSITAS INDONESIA
TUJUAN DARI PROGRAM PENCEGAHAN

untuk menurunkan angka

insidens dan kematian
karena kanker serviks
 §2.1 Natural History of Disease
Natural history of disease ≡ progression of disease in
an individual over time.
 Natural History of Cervical
Cancer:
Current Understanding
Normal Cervix

About 60% HPV Infection

regress
within HPV-related Changes
2-3 yrs

Low-Grade SIL (Atypia, CIN I)

Cofactors
About 15% progress within 3-4 yrs High-Risk HPV
(Types 16, 18, etc.)
High-Grade SIL (CIN II, III/CIS)

30% - 70% progress within 10 yrs

Invasive Cancer Source: PATH 1997.

 Natural History of Disease
Age of Individual
20 30 40 45 50 55 60

Birth Exposure Cells Screened Symptom Death

Neoplasia Exfoliate Diagnosis Diagnosis

Total Pre-Clinical Phase (TPCP)

TPCP: Begins at the initiation of disease; ends when the

disease is clinically manifested (25 years in this example)
 CERVICAL CANCER
RISK FACTORS

• HPV EXPOSURE
EARLY ONSET OF INTERCOURSE

MULTIPLE PARTNERS OR PARTNERS

WITH MULTIPLE PARTNERS

PARTNER WHO PREVIOUS PARTNER HAD

CERVICAL CANCER
 CERVICAL CANCER
RISK FACTORS
• NOT RELATED TO HPV EXPOSURE

• SMOKING

• SOCIO ECONOMIC STATUS

• IMPAIRED IMMUNE STATUS

• YOUNG AGE
» IMMATURE IMMUNITY
 CERVICAL CANCER
RISK FACTORS
• STD
– Harm Mucous Membranes

• OCPs
– Glandular dysplasia

• DES Exposure
 Pencegahan primer
• Adalah upaya pencegahan yg dilakukan
saat proses carcinogenesis belum mulai
(pd periode pre-patogenesis) dengan
tujuan agar tidak terjadi proses
carcinogenesis

• 1. Promosi kesehatan
2. Perlindungan khusus
 Prevention of Cervical
Cancer
 Cervical cancer is a preventable disease
 Primary prevention:
 Education to reduce high risk sexual
behaviour
 Measures to reduce/avoid exposure to HPV
and other STIs
 HPV vaccine
 Pencegahan sekunder
 Adadalah upaya pencegahan yg
dilakukan saat proses penyakit
sudah berlangsung namun belum
timbul tanda/gejala sakit
(patogenesis awal) dengan tujuan
proses penyakit tidak berlanjut
1. Early diagnosis & prompt
treatment
2. Disability limitation
 Prevention of Cervical
Cancer

 Secondary prevention:
 Treatment of precancerous
lesions before they progress to
cervical cancer (implies practical
screening test)
 Tingkat pencegahan tertier
Bila telah terjadi defect /kerusakan struktural
ataupun disabilitas:

Adalahdeteksi&penatalaksanaan kanker
serviks dlm upaya

•mencegah terjadinya komplikasi

•Meningkatkan ketahanan hidup penderita

•Meningkatkan kualitas hidup pada kondisi

terminal
 
Downloaded from: StudentConsult (on 12 February 2009 08:15 AM)
© 2005 Elsevier
Five Criteria for a Cause  Effect Relationship

Criteria Risk Factor for Disease

1) Timing  Exposure occurs before development

of disease or during its progression
2) Strength  Is dose-dependent
 Cessation of exposure can modify disease
3) Prevalence  Occurs in multiple populations
4) Relationship to  Is independent
other risk factors  Can also act synergistically
5) Plausibility  Produces structural‡ or functional changes
which are events in mechanism of disease

‡
anatomic or molecular
Taxonomi Penelitian Epidemiologi

• Berdasarkan pengambilan
informasi faktor sebab & akibat

• Berdasarkan ada tidaknya

perlakuan
Berdasarkan penelusuran
sebab-akibat
a. Tak ada:
- Penelitian diskriptif
Survey,studi cross sectional

b. Ada:
1. Ke depan (forward looking): dari exposure ke
outcome
a. Kohort prospektif
b. Studi intervensi

2. Ke belakang (backward looking) dari outcome ke

exposure
a. Kasus-kontrol
Berdasarkan pengambilan informasi
faktor sebab & akibat
1. Informasi status sebab & akibat pada saat
yang sama: Studi kros-seksional

2. Informasi status sebab & akibat pada saat yang

berbeda (sebab yg terjadi waktu yg lalu atau
sedang berjalan):
Studi longitudinal:
a. Studi kasus-kontrol
b. Studi kohort
c. Studi intervensi
 Study Design Exercise

DZ
-

DZ

E
ati onal
bs e rv
O
Study
E

Cross-Sectional Study
 Study Design Exercise

DZ
E

E -

ati onal
bs e rv DZ
O
Study
E

Case-Control Study
 Study Design Exercise

v at ional DZ
Obser
Study
E
DZ

DZ
DZ
E

-
DZ

Cohort Study
 Prinsip penelitian
intervensi/eksperimental
 PENELITIAN
EPIDEMIOLOGI

PENCEGAHAN SEKUNDER :

SCREENING
 VALIDITAS

KEMAMPUAN DARI SUATU

PEMERIKSAAN/TEST UNTUK
MENENTUKAN INDIVIDU MANA YANG
MEMPUNYAI PENYAKIT/BERISIKO
(TIDAK NORMAL) DAN
INDIVIDU MANA YANG TIDAK
MEMPUNYAI PENYAKIT
(NORMAL/SEHAT).
 VALIDITY

The degree to which the results of a

measurement corresponds to the true state
of the phenomenon being measured

If the findings can be taken as being a

reasonable representation of the true
situation
 EXTERNAL VALIDITY
(generalizability)

The degree to which the results of an

observation hold true

If the study was repeated in the same

population using the same methods,
approximately the same results would be
obtained
 External validity:

 Characteristics of study participants (e.g.,

age, disease spectrum).
 Test cut-off point definition (test negative
versus positive).
 Definition of disease.
 All affect generalizability and
comparability between studies.
 INTERNAL VALIDITY

The degree to which the results of an

observation are correct for the subjects
being studied
 Internal validity:

 Avoidance of misclassification bias:

 Accepted gold standard used as reference test; no
time lag between new test and reference test.
 Avoidance of information bias:
 Assessment of the different tests, independent of all
relevant clinical information and other test results.
 Avoidance of verification bias:
 The reference standard is applied to the full study
population.
INDIKATOR UTK MENILAI
VALIDITAS

1.SENSITIVITAS

2.SPESIFISITAS
 PROGRAM PENCEGAHAN SEKUNDER
SKRINING

 Mendeteksi pre kanker serviks (diagnosa dini)

dengan menggunakan test skrining yang tepat guna
.

 Mengobati kanker serviks sedini mungkin untuk

mencegah progressivitas dari kanker tersebut.

 Meng follow up mereka yang hasil skrining test

positif untuk membatasi drop out antara waktu dari
setelah test skrining dan waktu pengobatan
Estimation of test characteristics:

Cross-sectional study

Population sample

Screening test Positive / Negative

comparison
Reference test Diseased / Not diseased
 ACCURACY OF SCREENING TESTS

Test No. of women Sensitivity % Specificity %

(study sites) (range in study sites) range in study sites)
Cytology 22,633 (5) 58 (29-77) 95 (89-99)

HPV testing 18,065 (4) 67 (46-81) 94 (92-95)

VIA 54,981 (11) 77 (58-94) 86 (75-94)

VIAM 16,900 (3) 64 (61-71) 87 (83-90)

Int J Cancer 2004; 110-907-13;

J Med Screening 2004; 11:77-84;
Int J Cancer 2004; 112: 341-7
Cancer Detect Prev 2004; 28: 345-51

Study
 Types of Epidemiologic Studies

E x p e r i m e n t a l S tu d y O b s e rv a ti o n a l S tu d y

R a n d o m i z e d C li n i c a l T r i a l D e s c rip tiv e S tu d y A n a l y t i c S tu d y

C o m m u n it y T r i a l
D e sc rip tiv e S tu d y C o h o rt S tu d y

C r o s s -S e c ti o n a l S tu d y C a s e - C o n tr o l S tu d y

E c o l o g ic S t u d y C r o s s -S e c ti o n a l S tu d y

E c o l o g ic S t u d y
 PENELITIAN
EPIDEMIOLOGI

DESIGN :

STUDI KROS SEKSIONAL

 KANKER SERVIKS KLINIK PUSAT DIAGNOSTIK DINI
YAYASAN KANKER INDONESIA
1993-1997

TAHUN PAP TEST KANKER %

SEVIKS
1993 8.677 29 0.33

1994 10.801 36 0.33

1995 8.477 32 0.38

1995 8.184 15 0.18

1996 8180 12 0.15

TOTAL 44.289 124 0.28

SKRIPSI KURNIA WIDYASTUTI 1998

 DISTRIBUSI PROPORSI INFEKSI HPV PADA
PENDERITA KANKER SERVIKS
KLINIK PDD YKI 199301997

INFEKSI TOTAL
HPV
N %

YA 11 8.9

TIDAK 113 91.1

TOTAL 124 100

SKRIPSI KURNIA WIDYASTUTI 1998
 KARAKTERISITIK PENGUNJUNG
DETEKSI DINI KANKER SERVIKS DI RS
KANKER DHARMAIS 2007
KARAKTERISTIK %

UMUR RATA-RATA 41.2 THN

MENIKAH 91.6 %
UMUR >20 MENIKAH 81.5 %
MENIKAH SEKALI 49.1%
PARITAS 2-3 ANAK 56.5%
TDK MENGGUNAKAN 82.6%
KONTRASEPSI
TDK PERNAH PAP SMEAR 82.1%
SBLMNYA
SARJANA 36.9%
TIDAK BEKERJA 49.8%
MEROKOK 11.4%
SKRIPSI ISTIATY SYAHRIANA 2008
PENGUNJUNG DETEKSI DINI KANKER
SERVIKS MENURUT HASIL PAP TEST
DI RS KANKER DHARMAIS

HASIL PAP TEST JUMLAH %

POSITIF 4 0.8
NORMAL 459 87.1
RADANG 49 9.3
RADANG TDK 2 0.4
SPESIFIK
CANDIDIASIS 5 0.9
INKONKLUSIF 8 1.5

TOTAL4 527

SKRIPSI ISTIATY SYAHRIANA 2008

 TES PAP,TES HPV&
SERVIKOGRAFI SBG PEM.AN
TRIASE UTK TES IVA POSITIF
 WANITA USIA 25-45 THN
 DARI 8 PUSKESMAS & KLINIK BERSALIN
DI JAKARTA PUSAT & TIMUR
 DILAKSANAKAN OLEH 14 BIDAN

TEST IVA (n) POSITIF %

1250 130 10.4%

DISERTASI DWIANA OCVIYANTI

JENIS POSITIF SENSITIVITAS SPESIFISITAS PREDIKSI
PEMERIK N (%) % % +
SAAN %
TEST IVA 67 (51.5) 51.5
PAP STLH
IVA 33 (25.4) 40 90
82
HPV STLH
IVA 19(14.6) 16 87
58
SERVIKO
GRAFI 36(29.3) 56 97
STLH IVA
94
PAP&HPV
STLH IVA 45(34.6) 49 81
73
PAP&SERV
IKOGRAFI 57(46.3) 80 87
STLH IVA
86
HPV&SERV 78
IKOGRAFIS 46(37.4) 59 84
TLH IVA
PAP,SER,H
PV STLH 64(52) 80 76
IVA
77
 PENELITIAN
EPIDEMIOLOGI

DESIGN :

STUDI KASUS KONTROL

 HUBUNGAN RIWAYAT REPRODUKSI & POLA
KONSUMSI THD NIS DI PUSKESMAS PILOT
PROJECT DETEKSI DINI KANKER SERVIKS
KAB KARAWANG

 Design studi : kasus kontrol

 KASUS: POSITIF NIS DGN PEMERIKSAAN IVA

– (138)

 KONTROL: NEGATIF DGN PEMERIKSAAN IVA

– (138)

THESIS SUSMURNI OKTAVIA 2010

 HUBUNGAN RIWAYAT REPRODUKSI & POLA
KONSUMSI THD NIS DI PUSKESMAS PILOT
PROJECT DETEKSI DINI KANKER SERVIKS
KAB KARAWANG

HASIL ANALISA MULTIVARIAT REGRESI LOGISTIK

VARIABEL Β P WALD ODD 95%
BEBAS RATIO CI

PEKERJAAN 0.902 0.001 2.46 1.42-4.25

JML PSNG 1.792 0.000 6 2.74-13.12

SEKSUAL

PARITAS 0.907 0.002 2.48 1.41-4.35

THESIS SUSMURNI OKTAVIA 2010

Smoking and oral contraceptives as risk
factors for cervical carcinoma In situ

Our nested case-control study

was based on a study population
comprising all women resident in
Uppsala county, with a total
population of approximately
281,000 individuals, any time
from 1969 through 1995
Smoking and oral contraceptives as risk
factors for cervical carcinoma In situ

Eligible for the study were those

women in the cohort who were
alive and available for personal
interview at the start of the study
(January 1, 1996).

Thus, a total of 373 risk sets (373

cases and 373 matched controls)
were included in the matched
analyses.
Smoking and oral contraceptives as risk
factors for cervical carcinoma In situ
Table I. OR AND 95% CI OF CERVICAL CARCINOMA IN SITU IN
RELATION TO SMOKING HABITS

Number
Variable of
95% CI 95% CI
Smoking status cases/ Crude Adjusted
controls OR1 OR2

Never 105/168 1 1 —
Ex-smoker 67/61 1.67 1.08–2.56 1.47 0.92–2.34
Current smoker 201/144 2.28 1.62–3.21 1.94 1.32–2.85
p<0.0014 p<0.0054
 Table OR AND 95% CI OF CERVICAL CARCINOMA IN SITU IN
RELATION TO OC USE
Variable
Number of Crude Adjusted
Combined 95% CI 95% CI
cases/controls OR1 OR2
estrogen-progestin

Never 48/84 1 — 1 —
1.38– 1.17–
Ex-user 241/239 2.22 1.98
3.56 3.33
2.09– 1.91–
Current user 77/48 3.78 3.64
6.85 6.93
Missing 7/2
p < 0.0013 p < 0.0013
 PENELITIAN
EPIDEMIOLOGI

DESIGN :

STUDI KOHORT
Studi KOHORT /longitudinal
 We restricted eligibility to female University
of Washington undergraduates who were 18
to 22 years old and
 who had never had vaginal intercourseor had
first had intercourse with one malepartner
within the previous three months.
 In addition, the women had to have a cervix,
could not be pregnant, had to be in good
general health, and had to be able to provide
written informed consent.
Assessment periods
Berdasarkan ada tidaknya perlakuan

• Experimental
– Peniliti mempunyai kontrol terhadap
pemaparan

• Observational
– Peneliti mengamati pemaparan yg
terjadi secara secara alamiah
(Peneliti tidak memanipulasi
pemaparan)
 PENELITIAN
EPIDEMIOLOGI

DESIGN :
RANDOMIZED
PLACEBO CONTROLLED TRIAL
Randomized controlled trials (RCTs):

Target population

R
Intervention Testing Control
plus group
treatment
group

CxCa CxCa
Outcome incidence Comparison incidence
or mortality or mortality
Randomized controlled trials (RCTs):

 Random assignment of people/communities to

one group or another to ensure comparability.

 Standardization of the intervention—test AND

treatment modalities—to ensure comparability
and reproducibility.

Best methodology, but very labor intensive.

 PENELITIAN
EPIDEMIOLOGI

PENCEGAHAN PRIMER :

HPV VACCINE
 PENELITIAN
EPIDEMIOLOGI

TUJUAN :

EFFICACY
HPV VACCINE
 Sustained efficacy up to 4·5 years of a bivalent L1
virus-like particle vaccine against human
papillomavirus types 16 and 18: follow-up from a
randomised control trial
 double-blind, randomised, placebo-
controlled trial reported in 2004.

 Included women who originally received all

three doses of bivalent HPV-16/18 virus-like
particle AS04 vaccine (0·5 mL; n=393) or
placebo (n=383).

 Assessed HPV DNA, using cervical

samples, and did yearly cervical cytology
assessments
Effectiveness consideration:

Showing that a prevention program protocol is

efficacious using a RCT does not mean it is
effective under normal program conditions.

 RCT outcome = result of strict application of a

standardized protocol under ideal conditions
(efficacious).

 Effectiveness = expected improvements in health

resulting from routine service delivery programs.
Alliance for Cervical Cancer
Prevention (ACCP) work:

Usefulness of Pap test in reducing cervical cancer mortality is

generally acknowledged in countries with well organized
screening programs, but successful implementation is
challenging in low-resource settings.

 In response to these challenges, ACCP is conducting:

 Cross-sectional studies to estimate characteristics of low-
cost tests in different settings.
 RCTs to answer efficacy questions for these screening tests and
treatments, integrated into specific service delivery approaches.
 Pilot projects to assess the effectiveness of alternative
prevention algorithms in routine practice.
 Conclusions:

 Determining a test’s characteristics requires a

rigorous cross-sectional study design

 Selecting a good test does not necessarily mean you

will have an effective prevention program

 RCT study designs are best for assessing program

efficacy, but are very labor intensive.

 Evaluations of pilot projects and observational study

designs are useful for assessing the effectiveness of
chosen prevention strategies in routine settings.