This document discusses various methods for early detection of cervical cancer, including the Pap smear test and its limitations. It describes the Pap smear as the gold standard screening method but notes it has false negative and positive rates of 42% and limitations with specimen collection and analysis. The document summarizes alternative screening methods like ThinPrep, HPV testing, visual inspection with acetic acid, and a computer-assisted screening method called PapNet. It also provides details on cervical cancer classifications systems like The Bethesda System and explains concepts like ASCUS, LGSIL, HGSIL, and adenocarcinoma.

1. MODALITY of EARLY
DETECTION
CERVICAL CANCER
Poedjo Hartono SpOG (K)

2. Prevention of Cervical
Cancer
 Cervical cancer is a preventable
disease / STD
 Primary prevention:
 Education to reduce high risk
sexual behaviour
 Measures to reduce/avoid
exposure to HPV and other STIs
 Secondary prevention:
 Treatment of precancerous lesions
before they progress to cervical
cancer (implies practical screening
test)

3. Secondary Prevention of
Ca.Cx.
 Key Point is to detect
precancerous lesions .
 Answer: - A good screening
method
 PAP smear test is considered to be
the gold standard – Has limitations
?
 Alternatives to Pap Smear – What
are they?

4. Qualities of a Good
Screening Test?
Safe
Practical
Affordable
Available
Effective

6.  PAP smear test is the gold
standard – But has limitations*.

7. PAP SMEAR
SCREENING
EARLY DETECTION
Rekomendasi “A”
(US Prevention Service Task
Force)

8. Pap SmearPap Smear
Pemeriksaan sitologi eksfoliatif dari
epitel serviks untuk mendeteksi
lesi prakanker secara dini

9. PAP SMEARPAP SMEAR
SensitivitySensitivity 29-59%29-59%
SpesifisitySpesifisity 97-100%97-100%
False negativeFalse negative 42%42%
Akurasi >> pd HSILAkurasi >> pd HSIL

10. FALSE NEGATIVEFALSE NEGATIVE
Medical problemMedical problem
Financial problemFinancial problem
Legal implicationsLegal implications

11. FALSE POSITIVEFALSE POSITIVE
Financial problemFinancial problem
Psychologic problemPsychologic problem

12. False NegativeFalse Negative
sampling errorssampling errors 2/32/3
detection errorsdetection errors 1/31/3
False positiveFalse positive
interpretation errorsinterpretation errors

13. •PENGAMBILAN SPECIMEN
•PROSES DAN ANALISA
SPESIMEN
•INFORMASI HASIL
•KEPUTUSAN
KLINIS
MASALAH PADA PAP
SMEAR

14. Persentase transfer sel epitel
pada kaca benda berdasarkan
variasi alat
6,5 % dengan kapas lidi / spatula6,5 % dengan kapas lidi / spatula
8,4 % dengan cytobrush8,4 % dengan cytobrush
18,1 % gabungan cytobrush dengan spatula18,1 % gabungan cytobrush dengan spatula

16. Tes pap
konvensional
Spesifisitas 98%, sensitifitas 51%
(berdasarkan 84 penelitian meta
analisis yang dilaporkan oleh The
Agency for Health Care Policy)
50% false negatif terutama disebabkan
inadequate sampling dan sample
transfer

17. MEASURED TO REDUCE ERRORS
Using cytobrush and Ayre
No more than 100 specimens a day
10% of the normal smear must be
manually re-screened

18. Perkembangan Terminologi Hasil Tes PapPerkembangan Terminologi Hasil Tes Pap
 1943 Papanicolaou
 1953 Displasia - Karsinoma Insitu (Reagan)
 1967 Neoplasia Intraepitel Serviks (Richart RM)
 1988 The Bethesda System
 1990 Modifikasi Neoplasia Intraepitel Serviks
 1990 British Society for Clinical Cytology
 1991 The Bethesda System
 2001 The Bethesda System

19. KLASIFIKASI PAPANICOLAOU
Kelas IKelas I : Tidak ditemukan sel atipik atau: Tidak ditemukan sel atipik atau
sel abnormalsel abnormal
Kelas IIKelas II : Sitologi atipik tetapi tidak: Sitologi atipik tetapi tidak
ditemukan keganasanditemukan keganasan
Kelas IIIKelas III : Sitologi sugestif tetapi tidak: Sitologi sugestif tetapi tidak
konklusif keganasankonklusif keganasan
Kelas IVKelas IV : Sitologi sangat sugestif: Sitologi sangat sugestif
keganasankeganasan
Kelas VKelas V : Sitologi konklusif keganasan: Sitologi konklusif keganasan

20. Sistem Deskriptif
Meliputi kriteria:
 Negatif (tidak ditemukan sel ganas)
 Inkonklusif (spesimen tidak memuaskan)
 Displasia (didapatkan sel-sel diskariotik)
 Positif (didapatkan sel-sel ganas)

21. Sistem Neoplasia Intraepitel Serviks (NIS)
Karena secara biologik tidak ditemukan perbedaan
antara displasia dan karsinoma insitu, keduanya
dianggap satu kesatuan penyakit yang hanya berbeda
tingkatannya, disebut NIS.
NIS 1 sesuai displasia ringan
NIS 2 sesuai displasia sedang
NIS 3 sesuai displasia berat dan karsinoma insitu

22. Sistem Pelaporan Klasifikasi BSCCSistem Pelaporan Klasifikasi BSCC
((British Society for Clinical Cytology 1980British Society for Clinical Cytology 1980))
 Tidak memuaskan untuk evaluasiTidak memuaskan untuk evaluasi
 NegatifNegatif
 Perubahan inti (Perubahan inti ( borderlineborderline))
 Sel diskariotik : ringan ,sedang danSel diskariotik : ringan ,sedang dan
beratberat
 Sel ganas invasif, skuamosa atauSel ganas invasif, skuamosa atau
adenokarsinomaadenokarsinoma

23. The Bethesda System
 Terminologi pelaporan hasil tes Pap terbaru yang
berorientasi klinik
 Perkembangan :
 1988 : Pengembangan sistem pelaporan sebagai
sistem terminologi yang seragam untuk panduan
penatalaksanaan klinik.
 1991 : Modifikasi, setelah implementasi pengalaman
klinik dan laboratorium aktual
 2001 : Reevaluasi, dengan adanya teknologi dan
penemuan baru

24. Padanan dari klasifikasi
Class I Class II Class III Class IV Class V
Normal Inflam
Mild Mod Sev
CIS
Cancer
D y s p l a s i a
Normal Atypia
CIN I CIN II
CIN III Cancer
K o i l o c y t o s i s
WNL
Benign
Cellular
Changes
AS
CUS
LGSIL HGSIL HGSIL Carcinoma
NEGATIF
AS
CUS
LGSIL HGSIL HGSIL Carcinoma

25. The Bethesda System
(TBS)
 Rekomendasi :
 Laporan sitopatologi adalah konsultasi medik
 Klasifikasi Papanicolaou sudah tidak layak
digunakan pada praktek diagnostik sitopatologi
modern
 Sistem Bethesda berfungsi sebagai petunjuk
pelaporan sitopatologi serviks / vagina.

26. Laporan sitopatologi adalah konsultasi medik :
Evaluasi diagnostik dan laporan menjadi
tanggung jawab ahli sitopatologi
Dokter perujuk wajib mencantumkan
informasi klinik yang berhubungan
Ahli sitopatologi harus menentukan
adekuasi spesimen
Laporan diagnostik mencakup rekomendasi dan
evaluasi diagnostik.
The Bethesda System (TBS)

27. Fiksasi tidak baik (artefak)Fiksasi tidak baik (artefak)

28. Apusan terlalu tebalApusan terlalu tebal

29. SITOLOGI NORMAL
Sel skuamosa Sel endoserviks

30. Sitologi Abnormal
ASCUS
• Sitoplasma mirip dengan sel Intermediet
• Nukleus 2-3x ukuran sel Intermediet
• Normokromatin sampai hiperkromatin ringan
• Nukleus bulat tanpa atau dengan minimal
iregularitas
• Tidak ada efek HPV
• Biasanya sel terisolasi (kecuali pada
atypical repair)

31. LG SIL / LIS derajat rendah
• LIS derajat rendah dahulu dilaporkan / sepadan dengan
 Pap III (Papanicolaou)
 Displasia ringan (Reagan)
 NIS I (Richart)
• LIS derajat rendah, meliputi :
 Displasia ringan/ NIS 1
 Infeksi HPV (tanpa gambaran displasia)

32. LGSIL / HPV
SEL KOILOSIT DISKERATOSIS

33. LGSIL / NIS 1

34. HG SILHG SIL / LIS derajat tinggi/ LIS derajat tinggi
• LIS derajat tinggi, meliputi:
• Displasia sedang /NIS 2
• Displasia berat / NIS 3 / karsinoma insitu
• LIS derajat tinggi dahulu dilaporkan / sepadan dengan
 Pap III-IV (Papanicolaou)
 Displasia sedang / berat /karsinoma in situ (Reagan)
 NIS 2 dan NIS 3 (Richart)

35. HGSIL

36. KARSINOMA SEL
SKUAMOSA

37. Perluasan subkategori AGUS (Atypical Glanduler Cells of Undetermined
Significance) pada TBS 1991, menjadi:
• Atipik (NOS) : sel endoserviks, endometrium,
glanduler
• Atipik (favor neoplastic) : sel endoserviks, glanduler
• Adenokarsinoma insitu serviks (AIS)
• Adenokarsinoma : endoserviks, endometrium,
ekstrauterin, NOS
Atypical Glanduler Cells (AGC) TBS 2001

38. ATYPICAL GLANDULAR CELLS

39. ADENOKARSINOMA
INSITU SERVIKS

40. ADENOKARSINOMA
SERVIKS

41. Cervical Cancer
Screening
 Automated papsmear
 Thin Prep (Liquid base cervical cytology)
 Cervicography
 Molecular (HPV/DNA) tests
 Colposcopy
 Visual inspection with acetic acid (VIA)
 Visual inspection with lugol’s iodine (VILI)
 Visual inspection with acetic acid and magnification (VIAM):
Gynescope or Speculoscopy
Other Options: -

42. PAP NET

43. PAP NET

44. Hasil PAP NET
setelah di baca oleh Ahli Sitologi

45. PAP NET
 Pap Net meningkatkan akurasi skrining
apusan serviks dengan mengurangi
angka negatif palsu.
 Reskrining Pap Net dari hasil negatif
skrining manual didapatkan 4,8 %
abnormal (Ferenczy,dkk. 1996)

46. Kelebihan Pap Net
♦ Menurunkan angka negatif palsu dan positif palsu
♦ Meningkatkan akurasi pemeriksaan Tes Pap
♦ Menurunkan angka kesalahan skrining
♦ Menurunkan waktu pemeriksaan skrining Tes Pap
♦ Mengurangi angka kelelahan skrining
♦ Jumlah sampel yang diperiksa dapat dalam jumlah besar
Kekurangan Pap Net
♦ Harga mahal dan tidak ekonomis
♦ Masih memerlukan tenaga ahli sitologi untuk menegakkan
diagnosis

47. THIN PREP
LIQUID BASED CERVICAL CYTOLOGY

48. Thin Prep
Preparasi sediaan Tes Pap dengan teknik
Thin-Layer dimana hasil smear
dapat berupa satu lapisan sel-sel tidak
bertumpuk dan tidak tertutup oleh darah,
mukus, atau debris lainnya dengan
Tujuan Thin Prep
untuk meningkatkan akurasi hasil
Tes Pap

51. Pap konvensional Thin prep

52. A S C U S
Thin prepPap konvensional

53. Kelebihan Thin Prep
• Menurunkan angka negati palsu dan positif palsu
• Menurunkan angka Kesalahan interpretasi
• Meningkatkan akurasi Tes Pap
• Mengurangi kelelahan skriner
Kekurangan Thin Prep
Harga mahal

58. I V A
Sankaranarayanan dkk (Thailand)
Efektif, aman, praktis, murah
Tidak invasif
Oleh dokter – bidan - paramedis

59. Diagram Histopatologi Epitel
Skuamosa Serviks Normal dan
Displasia

60. ASAM
ASETAT

61. Gambaran Visual dengan Aplikasi
Asam Asetat pada Lesi Prakanker
Sebelum pemberian asam asetat Setelah pemberian asam asetat

62. What Is VIA
 Looking at the cervix to detect
abnormalities after applying acetic acid
 Acetic acid is used to enhance and
“mark” the acetowhite change of a
precancerous lesion or actual cancer
 Sensitivity and specificity of VIA - 70-
92%
 Positive Predictive Value - 15-20%
“Visual Inspection after Acetic Acid “
Also known as “Aided Visual Inspection of Cervix”, or
“ Acid Acetic Test”

63. Effects of acetic acid
1. Acetic acid coagulates mucus, which becomes easier
to remove.
-allows a better view of the cervix
2. Acetic acid constricts the superficial vessels and
blows up the columnar papillae so that they become
pale.
- allows a better view of the squamocolumnar junction
3. Acetic acid causes dehydration of the cells and
coagulation of cellular proteins, thereby reducing the
transparency of the epithelium
- allows a better recognition of dysplastic epithelium

64. Objectives Of Acetic
Acid Examination
 Locate the squamocolumnar
junction
 Identify any lesion & its limits
 Decide whether the lesion is CIN
 Determine whether invasion is
possible
 Select a site or sites for biopsy if
appropriate

65. What May Be Acetowhite
 All acetowhite patches are not cancer
 Any of these epithelial changes can
become acetowhite
 Healing or regenerating epithelium
 Congenital transformation zone
 Inflammation
 Immature squamous metaplasia
 HPV infection
 CIN / CGIN
 Adenocarcinoma
 Invasive squamous cell carcinoma

66. Why VIA as an
Alternative in
Low-resource Settings?
 Non-invasive, easy to perform and
inexpensive
 Can be performed by all levels of
healthcare workers, in almost any setting
 Skills consistent with service delivery
tasks performed by nurses/midwives in
MCH/FP clinic settings
 Results are available immediately
 →

67. Why VIA as an
Alternative in
Low-resource Settings?
 Initial treatment can be provided at
the time of the examination
 All system requirements are
available locally
 Potential for immediate link to
treatment
 Approach suitable for lowest-
resource settings
 ***

81. Servikografi
Kamera yang menghasilkan panoramik
gambar serviks dengan resolusi tinggi.
Tes pelengkap yang meningkatkan
sensitivitas dan spesifisitas tes pap untuk
mendeteksi lesi prakanker dan kanker serviks.

82. Why is cervicography
needed?
1.Screening
- the pap smear alone is not sensitive enough
- broadened cytology criteria decreases specificity
- triage of increased numbers of atypical smears
2.Documentation
- Evaluation and follow-up
- Research
- Teaching

83. Cervicography
Sensitivity –high
Specificity - low
High false-positive rate
Negative predictive value-almost 100%
Drawback-cannot evaluated endocervix

84. Tes HPV
HPV sulit dikultur
Tes deteksi dan tipe HPV
3 tes
Hybrid Capture 2 ( HC2)
Polymerase Chain Reaction (PCR)
In Situ Hybridization (ISH)

85. HPV Risk TypesHPV Risk Types
HPV DNA Test uses two RNA Probe cocktails
to differentiate between carcinogenic and low
risk HPV types
 Low risk
 6, 11, 42, 43, 44
 High risk
 16, 18, 31, 33, 35, 39, 45, 51, 52,
56, 58, 59, 68

86. Source-Program for Appropriate Technology in Health [PATH] 1997.
Effective Safe Practical Affordable Available
Visual
Inspection: AA
Yes Yes Yes Yes Yes
Visual
Screening:
Unaided
No Yes Yes Yes Yes
Automated Pap
Screening
Yes? Yes ? No No
HPV Screening Yes Yes ? ? Yes
Cervicography Yes? Yes ? ? Yes
HPV Vaccine ? ? Yes ? No
Approaches to Cervical Cancer
Prevention in low resource
settings
Alternatives to Pap Smear: -Alternatives to Pap Smear: -

87. Early detection of cervical
cancer
Screening test (Tes skrining)
Adjunctive test (Tes pelengkap)
Diagnostic test (Tes diagnostik)

88. Screening test
Pap test
Conventional
Papnet (computer assisted screening)
Thinprep (liquid base, thin layer cytology)
VIA (Visual Inspection with Acetic acid)

89. Adjunctive test
Cervicography
HPV-DNA test
Speculoscopy

90. Diagnostic test
Colposcopy

93. COLPOSCOPY
Abnormal colposcopySatisfactory unsatisfactory
Diagnostic
Conisation
CIN
Invasive
Biopsy/LEEP
Destruction
Excition
See and treat
Invasive
CIN
free margin
FUCIN 1 : FU
CIN 2 : Cryosurgery/ LEEP/LLETZ
CIN 3 : LLETZ

94. TREATMENT
MODALITY
Location, Grading,
Size
OBSERVATION
CHEMICAL
Interferon
Retinoid
5-FU topical
Excition
LEEP/LLETZ.
Conisation
Histerectomy
Destruction
Cryosurgery
E. Coagulation
Laser vap

95. Comparison of therapeutic
Modalities for Cervical
Intraepithelial Neoplasia
Procedure Rates Technical
Ease
Equipment
Cost
Complication
Rates
Primary
Cure
Cryosurgery +++ +++ ++ 80%
Loop electrosurgical
excision procedures
+++ ++ +++ 95%
Laser ablation + + +++ 95%
Laser excision + + ++ 95%
Cold-knife conization ++ +++ + 98%
+, low; ++, medium; +++, high

96. Treatment of Cervical Cancer at glance
CIN 1 CIN 2 CIN3 .0 .Ia1 Ia2 I b1 Ib2 II a II b III StgIV
LGSIL HG SIL
Cryo
Cauter
LEEP
Cryo
LEEP
LLETZ
Cryo2x
Cone
SH
SH Rad.H Rad.H Rad.H Rad.H
Radiation
Chemotherapy
Area which diagnostic conization have a role

97. CONIZATION :
1. Cone biopsy = Cold knife conization
the surgical removal of
a cone shaped of cervical tissue
that is examined under a microscope
to help detect or rule
out the presence of cancer
2. LLETZ 
(Large loop excision of the transformation zone)
1981 World Congress of Colposcopic and cx ca
Cartier small loop
US LEEP

98. CONIZATION :
1. Diagnostic
2. Treatment