10 06 MAR MARET ET

(1)

06 MARET 2017

Om Swastyastu

(2)

INFEKSI HPV DAN

PERKEMBANGAN LESI

PRAKANKER SERVIKS

I N.G. BUDIANA

Divisi Onkologi-Ginekologi,

Departemen Obstetri & Ginekologi,

FK UNUD/RSUP Sanglah Denpasar

(3)

• Lesi Prakanker/Kanker Serviks:



Kausa:

Human Papilloma Virus



Karsinogenesis

• Lesi Prakanker Serviks:



Padanan klasifikasi



Perjalanan alamiah



Pencegahan

(4)

• Kanker Ke-2 tersering pada perempuan

Indonesia

1

• _{Hampir 70% sudah pd stadium lanjut}

(> stage IIB)

2

• _{Cakupan Skrining 24,4% (ideal ~ 80%)}

3,4

1).IARC.GLOBOCON 2012

2) INASGO Cancer Registry. 2016

3) HPV Information Centre. Human Papillomavirus and Related Disease Report. 27 July 2017. Available at www.hpvcentre.net

(5)

Sebanyak 58 kasus baru kanker

serviks terjadi setiap harinya.

1 26 wanita Indonesia meninggal

setiap hari karena kanker serviks

1

5

Globocan data 2012

1 BEBAN KANKER SERVIKS DI INDONESIA

Tingkat Kematian, Insidensi, Prevalensi

5 Tahun Tertinggi diantara

Negara-negara di Asia Tenggara

1 _!!!!!

WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human

Papillomavirus and Related Cancers in Indonesia. Summary Report 2014-08-22. Available at www.

Hpvcentre.net

(6)

• Analisis dari 932 spesimen dari wanita di

22 negara menunjukkan prevalensi DNA

HPV pada kanker serviks: 99,7%

HPV adalah penyebab utama

kanker serviks

HPV dan Kanker Serviks

(7)

• HPV ditemukan pada pasien-pasien

kanker serviks: 95,9%

• Sedangkan pada kontrol: 25,4%

Human Papilloma Virus

Di INDONESIA :

De Boer MA, Vet JNI, Azis MF, Cornain S, Purwoto G, van den Akker BEWM, Dijkman A, Peters

AAW, Fleuren GJ. Humanpapilloma virus and other risk factors for cervical cancer in Jakarta,

Indonesia. Int J Gynecol Cancer 2006;16:1809-1814

(8)

• >100 types identified

2 • ~30–40 anogenital

2,3

– Oncogenic*

,2,3

• HPV 16 and HPV 18

types account for the

majority of worldwide

cervical cancers.

4 – Nononcogenic**

• HPV 6 and 11 are most

often associated with

dysplasia and external

anogenital warts.

3

1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott-Raven; 2001:2197–2229. 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, Castellsagué X, et al. Int J Cancer. 2004;111:278–285.

Non enveloped

double-stranded DNA virus

1

(9)

80+%

~40%

~100%

60-90%

~100%

Percentages represent cases attributable to HPV infection 1.Braaten KP et al. Rev Obstet Gynecol. 2008;1:2–10. 2.Hoots BE et al. Int J Cancer. 2009;124:2375–2383.

3.IARC. IARC monographs on the evaluation of carcinogenic risks to humans. Human papillomaviruses. Vol 90. Lyon, France: IARC, 2007.

Kanker

Serviks

1,3

Kanker

Vulva

1

Kanker

Vagina

1

Kanker

Anal

1-3

Kutil

Kelamin

1,3

12-70%

Kanker

Orofaring

3

45%

_Cancer

Penile

3

Tipe kanker High risk

group-16,18,31,33,45,52,58

Tipe non-kanker

grup low risk –

6,11.

(10)

Rute seksual

85 %

Rute Non Seksual

15 %

Kontak Genital :

• Hubungan

senggama

• Genital-genital

• Anal-Genital

• Oral-genital

Extragenital :

• - pakaian

- handuk

- surgical gloves

- biopsi forceps

Vertikal

ibu

Neonatus

Saat lahir

Respiratory

papilomatosis

Horizontal

• Genital-finger

• Ujung jari kuku

1. F.Xavier Bosch et al. International Journal of Gynecology and Obstetrics (2006) 94 (Supplement 1), S8-S21; 2. Sonnex X et al. Sexually Transmitted Infections 1999 Oct;75(5):317-9

(11)

• >100 tipe HPV telah teridentifikasi

• HPV tipe 16 dan 18 mayoritas penyebab

kanker serviks di seluruh dunia

• HPV tipe 6 dan 11 yang paling banyak

berhubungan dengan external

anogenital warts

Human Papilloma Virus

1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott-Raven; 2001:2197–2229. 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, Castellsagué X, et al. Int

(12)

HPV Types

Lead to:

Low-Risk

High-Risk

HPV 6, 11,

40 ,

42, 43, 44,

54, 61,

70, 72, 81

HPV 16, 18,

31, 33, 35, 39, 45,

51, 52, 56, 58, 59,

68 , 73, 82

Benign cervical

changes

Genital warts

Precancer cervical

changes

Cervical cancer

Anal and other cancers

1. Cox. Baillière’s Clin Obstet Gynaecol. 1995;9:1.

2. Munoz et al. N Engl J Med. 2003;348:518.

(13)

Tipe HPV berdasarkan jenis histopatologi

• Adenocarcinoma: dominan HPV tipe 18

(56%)

• Squamous cell carcinoma: dominan HPV tipe

16 (51%)

• Adenosquamous: dominan HPV tipe 18 (46%)

Human Papilloma Virus

Schellekens MC, Dijkman A, Azis MF, Siregar B, Cornain S, Kolkman S, Peters LAW, Fleuren GJ.

Gynecologic Oncology 93 (2004):49-53

(14)

• Virus DNA, tdk berkapsul

• Genom: 8000 pasang

basa

• Kapsid:



Kapsid Mayor (L1): 80%

dari total protein



Kapsid Minor (L2)

(15)

Human Papilloma Virus

• Genom virus terbagi :

–

Early region

(E): transkripsi, replikasi dan

transformasi virus

–

Late region

protein (L): mengkode protein

kapsid virus

–

Long control region (LCR)

: mengandung

elemen pengontrol transkripsi dan replikasi

dan

viral origin replication

(16)

Fungsi Protein HPV:

Human Papilloma Virus

________________________________________

E1

E2

E4

E5

E6

E7

L1

L2

________________________________________

Replikasi virus

Replikasi dan transkripsi virus

Siklus pertumbuhan dan pematangan virus

Transformasi virus

Onkoprotein, berikatan dengan p53

Onkoprotein, berikatan dengan pRb

Mengkode protein kapsid mayor

Mengkode protein kapsid minor

(17)

(18)

(19)

1.Stanley M. Vaccine 2006; 24: S106-13, 2.Tindle, Nat Rev Cancer 2002; 2, 59, 3.Stanley M. Vaccine 2006; 24: S16-22, 4. Stanley M. HPV Today 2007; 11: 1-16

Local infection

1-4

Infect the epithelium through micro abration

No viremia

1-4

Enters basal epithelial cells, integrates DNA in host cell

1-4

Replication in the cells and remains entirely intraepithelial

Local immunosupression

1-4

1-4

Uses the natural life cycle of epithelial cells to release new viruses

1-4

Doesn’t cause cell deaths

No inflammation,

1-4

No attraction of immune cells

Poor exposure to Antigen Presenting Cells

(20)

Perjalanan infeksi HPV ?

Jika terinfeksi HPV

80% akan dibersihkan

dengan sistem immun

(kekebalan)

10- 20% berkemungkinan menjadi

infeksi persisten (menetap)

Risiko menjadi kanker serviks

Kebanyakan pria dan wanita yang telah berhubungan seksual, berisiko

terinfeksi HPV

Lebih dari 75% wanita yg berhubungan intim, pernah

terinfeksi HPV, puncak di antara umur 18-22 tahun

(21)

(22)

(23)

Biopsy

Regress

Persist

Progress Progress

Result

to CIS to Invasion

CIN1

57%

32%

11%

1%

CIN2

43%

35%

22%

5%

CIN3

32%

56%

--

>12%

CIN = Cervical Intraepithelial Neoplasia

Source: Öst

Ö

r AG. Int J Gynecol Pathol. 1993;12(2):186-192.

(24)

Anttilla, A., Aoki, D., Arbyn, M, Austoker, J., Bosch, X., Chirenje, Z. 2005. IARC Handbooks of Cancer Prevention: Cervic Cancer Screening. First Edition. IARC press: South Africa Selatan. p. 1-242

(25)

Lesi Prakanker Serviks

• Infeksi HPV, CIN-1/displasia ringan

CIN derajat rendah (LSIL)

• CIN-2/displasia sedang, CIN-3/displasia berat,

karsinoma insitu

(26)

Pencegahan Primer

Strategi Pencegahan Kanker Serviks

• Menghilangkan/mengurangi risiko kanker

serviks pd individu normal:



Edukasi/Promosi

(27)

Vaksinasi HPV diprioritaskan untuk individu yang naïve

terhadap HPV yaitu target usia 9-13 tahun.

(WHO position paper 2014)

Masih bisa

menerima

manfaat dari

vaksinasi HPV

World Health Organization, United Nations Population Fund. Preparing for the Introduction of HPV Vaccines: Policy and Programme Guidance for Countries. World Health Organization; 2006. World Health Organization. Weekly Epidemiological Record. 2009;15(84):117–132.

US FDA. FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human Papillomavirus. Available at

http://www.fda.gov/bbs/topics/NEWS/2006/NEW01385.html.2006. Accessed October, 2007.

The American College of Obstetricians and Gynecologists. Human Papillomavirus Vaccination. ACOG Committee Opinion No. 344. ObstetGynecol. 2006; 108 : 699 – 705

(28)

REKOMENDASI WHO

World Health Organization, United Nations Population Fund. Preparing for the Introduction of HPV Vaccines: Policy and Programme Guidance for Countries. World Health Organization; 2006. World Health Organization. Weekly Epidemiological Record. 2009;15(84):117–132.

US FDA. FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human Papillomavirus. Available at

http://www.fda.gov/bbs/topics/NEWS/2006/NEW01385.html.2006. Accessed October, 2007.

The American College of Obstetricians and Gynecologists. Human Papillomavirus Vaccination. ACOG Committee Opinion No. 704 Juni 2017

Vaksinasi membantu memberikan perlindungan

3 Vaksinasi direkomendasikan tanpa melihat aktivitas seksual

seseorang atau paparan sebelumnya terhadap HPV.

Vaksinasi direkomendasikan bahkan bila pasien tersebut

positif pada tes HPV DNA

4 Primary prevention:

(29)

Pencegahan Sekunder

Strategi Pencegahan Kanker Serviks

• Deteksi dini fase lesi prakanker dan

melakukan terapi secara adekuat sebelum

berkembang menjadi kanker serviks

(30)

Pencegahan Tersier

Strategi Pencegahan Kanker Serviks

• Upaya untuk mengurangi morbiditas dan

mortalitas pada pasien-pasien kanker

(31)

TAKE HOME MESSAGE

HPV sebagai penyebab kanker serviks

Perjalanan alamiah kanker serviks sudah

jelas, cukup waktu untuk mencegah

terjadinya kanker serviks

Dengan manajemen yang baik insidens

kanker serviks akan dapat diturunkan

1

2

(32)

Terima Kasih

Matur Suksma

FREE OF

CERVICAL

CANCER 2020

(33)

(34)

VACC-1249743-0000

CERTIFICATE

OF

ATTENDANCE

This is To Proudly Certify That:

-~---~---

has attended and successfully completed the program of

HPV Master Class

as

SPEAKER

March 10

th,

20181 Courtyard Marriot Hotel, Nusa Dua Bali

No. 21

1 1I

/

2018

/

SKP/

I

D

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-

BALI

Participant 4

SKP

,

Speaker 8

SKP,

Moderator 2

S

KP

,

C

om

mit

t

e

1 S

K

P

Head of POGI Bali