PENELITIAN EPIDEMIOLOGI UNTUK PROGRAM PENCEGAHAN KANKER SERVIKSRATNA 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 DiseaseNatural history of disease progression of disease in an individual over time.

Natural History of Cervical Cancer:Current UnderstandingNormal Cervix About 60% regress within 2-3 yrs HPV Infection HPV-related Changes

Low-Grade SIL (Atypia, CIN I) About 15% progress within 3-4 yrs High-Grade SIL (CIN II, III/CIS) 30% - 70% progress within 10 yrs Invasive CancerSource: PATH 1997.

Cofactors High-Risk HPV (Types 16, 18, etc.)

Natural History of DiseaseAge of Individual 20 30 40 45 50 55 60

Birth Exposure Cells Screened Neoplasia Exfoliate Diagnosis

Symptom Diagnosis

Death

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 EXPOSUREEARLY 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 tertierBila telah terjadi defect /kerusakan struktural ataupun disabilitas: Adalahdeteksi&penatalaksanaan serviks dlm upaya mencegah terjadinya komplikasi Meningkatkan ketahanan hidup penderita Meningkatkan kualitas hidup pada kondisi terminal kanker

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Five Criteria for a Cause Effect RelationshipCriteria1) Timing 2) Strength 3) Prevalence 4) Relationship to other risk factors 5) Plausibility

Risk Factor for Disease

Exposure occurs before

development of disease or during its progression

Is dose-dependent Cessation of exposure can modify disease Occurs in multiple populations Is independent Can also act synergistically Produces structural or functional changeswhich 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-akibata. Tak ada: - Penelitian diskriptif

Survey,studi cross sectionalb. Ada: 1. Ke depan (forward looking): dari exposure ke outcome a. Kohort prospektif b. Studi intervensi 2. Ke belakang (backward looking) dari outcome exposure a. Kasus-kontrol ke

Berdasarkan pengambilan informasi faktor sebab & akibat1. 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

ation v bser dy O u al St

E

Cross-Sectional Study

Study Design ExerciseE DZ E

ation v bser dy O u al St

E DZ E

-

Case-Control Study

Study Design Exercisen servatio Ob y al StudDZ E DZ DZ DZ E-

DZ

Cohort Study

Prinsip penelitian intervensi/eksperimental

PENELITIAN EPIDEMIOLOGIPENCEGAHAN SEKUNDER :

SCREENING

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

VALIDITYThe 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 VALIDITYThe 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 studyPopulation sample Screening test

Positive / Negative comparison

Reference test

Diseased / Not diseased

ACCURACY OF SCREENING TESTSTest Cytology HPV testing VIA VIAM No. of women (study sites) 22,633 (5) 18,065 (4) 54,981 (11) 16,900 (3) Sensitivity % 58 (29-77) 67 (46-81) 77 (58-94) 64 (61-71) Specificity % 95 (89-99) 94 (92-95) 86 (75-94) 87 (83-90)

(range in study sites)

range in study sites)

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 StudiesE R x p e a n C o r i m d m o m m e n t a i z e d u n it y l S tu d y O b s e r v a t i o n a l S S r t S t u tu t u

d y d

C D l i e n si c c a r il p T t i r v i ae l S A t u n d a y l y t i c T C r i a l D e s c r o E r i p t i v e S Ct u o d h y o

s s - S c o l o g

e c t i o nC a a l s S e t- u C d o y n t r o ic S tC u r d o y s s - S E c o l o g e ic c t i o S

t

PENELITIAN EPIDEMIOLOGIDESIGN : STUDI KROS SEKSIONAL

KANKER SERVIKS KLINIK PUSAT DIAGNOSTIK DINI YAYASAN KANKER INDONESIA 1993-1997TAHUN 1993 1994 1995 1995 1996 TOTAL PAP TEST 8.677 10.801 8.477 8.184 8180 44.289 KANKER SEVIKS 29 36 32 15 12 124 % 0.33 0.33 0.38 0.18 0.15 0.28

SKRIPSI KURNIA WIDYASTUTI 1998

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

INFEKSI HPV

TOTAL N 11 113 124 % 8.9 91.1 100

YA TIDAK TOTALSKRIPSI KURNIA WIDYASTUTI 1998

KARAKTERISITIK PENGUNJUNG DETEKSI DINI KANKER SERVIKS DI RS KANKER DHARMAIS 2007KARAKTERISTIK UMUR RATA-RATA MENIKAH UMUR >20 MENIKAH MENIKAH SEKALI PARITAS 2-3 ANAK TDK MENGGUNAKAN KONTRASEPSI TDK PERNAH PAP SMEAR SBLMNYA SARJANA TIDAK BEKERJA MEROKOKSKRIPSI ISTIATY SYAHRIANA 2008

% 41.2 THN 91.6 % 81.5 % 49.1% 56.5% 82.6% 82.1% 36.9% 49.8% 11.4%

PENGUNJUNG DETEKSI DINI KANKER SERVIKS MENURUT HASIL PAP TEST DI RS KANKER DHARMAISHASIL PAP TEST POSITIF NORMAL RADANG RADANG TDK SPESIFIK CANDIDIASIS INKONKLUSIF TOTAL4 JUMLAH 4 459 49 2 5 8 527 % 0.8 87.1 9.3 0.4 0.9 1.5

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 BIDANTEST IVA (n) 1250 POSITIF 130 % 10.4%

DISERTASI DWIANA OCVIYANTI

JENIS PEMERIKS AANTEST IVA PAP STLH IVA HPV STLH IVA SERVIKO GRAFI STLH IVA PAP&HPV STLH IVA PAP&SERVIK OGRAFI STLH IVA HPV&SERVI KOGRAFISTL H IVA PAP,SER,HP V STLH IVA

POSITIF N (%)67 (51.5) 33 (25.4) 19(14.6)

SENSITIVITAS SPESIFISITAS % %

PREDIKSI + % 51.5

40 16

90 87

82 58 94 73 86 78

36(29.3)

56

97

45(34.6)

49

81

57(46.3)

80

87

46(37.4)

59

84

64(52)

80

76

77

PENELITIAN EPIDEMIOLOGIDESIGN : 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 (138) DGN PEMERIKSAAN IVA

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 LOGISTIKVARIABEL BEBAS PEKERJAAN JML PSNG SEKSUAL PARITAS P WALD ODD RATIO 2.46 6 95% CI 1.42-4.25 2.74-13.12

0.902 1.792

0.001 0.000

0.907

0.002

2.48

1.41-4.35

THESIS SUSMURNI OKTAVIA 2010

Smoking and or al contraceptives as risk factor s for cer vical 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 or al contraceptives as risk factor s for cer vical 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 or al contraceptives as risk factor s for cer vical carcinoma In situ

T a b lIe

Tab le

PENELITIAN EPIDEMIOLOGIDESIGN : 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 EPIDEMIOLOGIDESIGN :

RANDOMIZED PLACEBO CONTROLLED TRIAL

Randomized controlled trials (RCTs):Target population

RIntervention Testing plus treatment group CxCa incidence or mortality Control group

Outcome

Comparison

CxCa incidence or mortality

Randomized controlled trials (RCTs):

Random assignment of people/communities to one group or another to ensure comparability. Standardization of the interventiontest AND treatment modalitiesto ensure comparability and reproducibility. Best methodology, but very labor intensive.

PENELITIAN EPIDEMIOLOGIPENCEGAHAN PRIMER :

HPV VACCINE

PENELITIAN EPIDEMIOLOGITUJUAN :

EFFICACY HPV VACCINE

double-blind, randomised, placebocontrolled trial reported in 2004.

Sustained ef ficacy up to 45 year s of a bivalent L1 vir us-like par ticle vaccine against human papillomavir us types 16 and 18: follow-up fr om a r andomised contr ol trial

Included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (05 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 lowcost 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 tests 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.