PRETEST 1

S YA H R I N I W D R . S P O G , M . K E S

KAN

LATAR BELAKANG

• Kanker serviks adalah kanker wanita tersering nomor 3 dari segi insiden (527.600

kasus baru) dan mortalitas (265.700 kematian) di seluruh dunia, setelah kanker

payudara dan kolorektal.

• Angka kejadian kanker serviks di Indonesia pada tahun 2012 sebesar 20.928 kasus

dengan angka kematian sebanyak 9.498. Kebanyakan pasien datang pada stadium

lanjut yaitu stadium IIB-IVB, sebanyak 66,4%.

• Human Papilloma Virus (HPV) sangatlah penting pada perkembangan neoplasma

serviks dan bisa dideteksi pada 99,7% kasus kanker serviks.

• 2 Tipe histologi dari kanker serviks terbanyak adalah karsinoma sel skuamous

(69% dari kanker serviks) dan adenokarsinoma (25%).

DEFINISI

• Kanker serviks adalah keganasan pada serviks yang disebabkan oleh infeksi

HPV grup onkogenik risiko tinggi; terutama HPV 16 dan 18 serta filogeniknya.

• Lebih dari 95% kanker serviks adalah tipe epithelial yang terdiri atas jenis

karsinoma sel skuamosa dan adenokarsinoma.

ETIOLOGI

Ada 4 langkah utama perkembangan kanker serviks:

• Infeksi HPV onkogenik pada epitel metaplasia dari zona transformasi serviks.

• Infeksi HPV persisten

• Perkembangan klon sel epitel dari infeksi virus persisten menuju pra kanker -

Perkembangan menjadi kanker dan invasi melalui membran basalis

• Infeksi HPV genital sangatlah umum, tidak menimbulkan gejala dan sering

Infeksi HPV terdeteksi pada hingga 99% wanita dengan

karsinoma serviks skuamosa. HPV adalah agen penyebab,

baik pada skuamosa dan adenokarsinoma serviks, tetapi

masing-masing tumor mungkin memiliki jalur karsinogenik

yang berbeda.

Secara umum, perkembangan displasia menjadi kanker invasif memerlukan beberapa

tahun, meskipun waktu dapat sangat bervariasi. Perubahan molekuler yang terlibat

dengan karsinogenesis serviks adalah kompleks dan tidak sepenuhnya dipahami.

Karsinogenesis saat ini diduga merupakan hasil interaksi antara paparan lingkungan,

imunitas, dan variasi genom sel somatik.

Patofisiologi

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Interaksi Faktor Risiko dengan sel serviks

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Peran Onkoprotein

Mekanisme HPV mempengaruhi

pertumbuhan dan diferensiasi sel

adalah melalui interaksi protein

virus E6 dan E7 dengan masing-

masing gen penekan tumor p53

dan Rb.

Protein E7 berikatan dengan

protein penekan tumor

retinoblastoma (Rb), sedangkan

E6 berikatan dengan protein

penekan tumor p53.

Penghambatan p53 mencegah

penghentian siklus sel dan apoptosis

seluler, yang biasanya terjadi ketika

DNA rusak, sedangkan

penghambatan Rb mengganggu

faktor transkripsi E2F, yang

mengakibatkan proliferasi seluler

yang tidak diregulasi.

Kedua langkah ini berperang penting

dalam transformasi maligna sel epitel

serviks dengan proliferasi sel yang tidak

terkontrol dan kegagalan sel dalam

memicu apoptosis sel.

FAKTOR RESIKO

Hubungan seks dini / berganti – ganti pasangan

Riwayat penyakit menular seksual

kondisi immunosupresi (HIV, penggunaan obat immunosupresi)

Merokok

Sosio ekonomi rendah

REKOMENDASI SKRINING SERVIKS ( ACOG/ AMERICAN COLLEGE OF OSTETRICIANS AND GYNECOLOGISTS)

JENIS PEMERIKSAAN DAN USIA FREKUENSI

Pap smear untuk wanita > 20 Tahun Setiap 1-3 tahun sekali

Pemeriksaan HPV DNA untuk wanita > 30

tahun

Setiap 1-3 tahun sekali

Pemeriksaan co testing Pap smear + HPV

DNA untuk wanita > 30 tahun

Setiap 1-3 tahun sekali

IVA untuk wanita > 20 tahun Setiap 1-3 tahun sekali

> 65 tahun tidak memerlukan skrining, jika hasil 2 kali pemeriksaan skrining

sebelumnya negatif

SKRINING SECARA SITOLOGIK

http://www.ps21.gov.sg/papsmear.jpg

http://www.brooksidepress.org/Pap/c5320x_lg.jpg

http://www.cervicalscreening.gov.hk/hp_taking_sampling.jpg

Source: EngenderHealth, Wright TC, 1996

Normal servik Servik dengan IVA +

IVA tes

• Vaksin dapat diberikan mulai usia 10-55

• Jadwal pemberian : 0, 1, 6 bulan (Bivalent); 0, 2, 6

bulan (Quadrivalent), pemberian ketiga bisa bulan

6-12. Interval minimum antara dosis pertama dan

kedua adalah 4 minggu, interval minimum antara

dosis kedua dan ketiga adalah 12 minggu.

• Pada usia 9-13 tahun, kedua vaksin dapat diberikan

pada 0, 6 bulan (2 kali pemberian)

REKOMENDASI VAKSIN HPV ( ACOG/ AMERICAN COLLEGE OF OSTETRICIANS AND GYNECOLOGISTS)

• Kontra indikasi: Hamil, Terkena Lesi Pra kanker

atau kanker terkait HPV, Demam tinggi,

Hipersensitivitas thd vaksin

• Boleh diberikan saat laktasi

• Penyimpanan Vaksin : pada suhu 2-8°C (tidak boleh

dibekukan)

• Cara pemberian IM (Deltoid)

• Booster : belum diperlukan

• Vaksin pada pria terbukti menurunkan insiden

kanker terkait HPV (10-26 th)

• Vaksin pada wanita yang telah terpapar HPV

terbukti menurunkan insiden kanker terkait HPV

• Bukan untuk terapi lesi pra kanker atau kanker

• Tidak menggantikan/ mengubah jadwal penapisan

KLASIFIKASI

PERJALANAN KANKER SERVIK

Sel Normal Lesi Pra Kanker Kanker

www.nccc-online.org

SERVIKS NORMAL ( LEHER RAHIM)

Lesi pra kanker serviks

GAMBARAN KLINIS KANKER SERVIKS

Jika kanker sudah metastasis : Sulit BAK dan mungkin gagal ginjal.

Nyeri BAK dan kadang2 kencing darah .

Bengkak di kaki

Diarrhea, atau nyeri di daerah anus atau BAB

berdarah

Mual, lemas, BB turun, nafsu makan turun, dan terasa

nyeri.

Konstipasi

Lubang Abnormal di leher rahim (fistula)

pembesaran kelenjar limphe di leher atau ketiak.

Penyebaran lanjut ke tulang, paru, usus atau otak

memberikan tanda – tanda abnormal.

Manifestasi Klinis

Pengobatan Kanker Serviks

Surgery

Radiation Therapy

External Radiation

Chemotherapy

Paliatif Therapy

TATALAKSANA

Stadium IA1

• Konisasi adalah pilihan terapi utama pada stadium IA1.

• Follow up pasca terapi dengan Pap smear dilakukan setiap 3 bulan selama 2 tahun,kemudian setiap 6 bulan pada 3 tahun berikutnya.

Stadium IA2

• Terapi yang direkomendasikan adalah histerektomi radikal tipe 2 dengan limfadenektomi kelenjar getah bening pelvis.

• Bila fungsi reproduksi masih diperlukan, pilihan terapi adalah :

• 1. Konisasi serviks dengan limfadenektomi pelvik, atau

• 2. Trakhelektomi radikal (abdominal, vaginal atau laparoskopi) dan limfadenektomi pelvik.

Stadium IB-IIA

• Terapi pembedahan untuk stadium IB-IIA adalah modified histerektomi radikal tipe 2 atau histerektomi radikal tipe 3 (laparotomi atau laparoskopi) dan limfadektomi pelvis.

Stadium IIB

• Kemoradiasi merupakan terapi standar pada stadium IIB

• Dosis radiasi eksternal yang disarankan adalah 45-50 Gy pada 180-200 cGy per fraksi.

Stadium IIIA – IVA

• Standar terapi adalah radiasi atau kemoradiasi : radiasi eksternal yang disarankan adalah 45-50 Gy + brachytherapy 2100 cGy atau modifikasi box system (bila brachytherapy tidak tersedia) dengan radiosensitizer

Stadium IVB

• Terapi Sistemik

• Radiasi paliatif untuk gejala lokal

• Penanganan paliatif yang komprehensif

PROGNOSIS & FOLLOW UP

• Dari review sistematik 17 percobaan klinis tentang follow up pasien pasca terapi kanker serviks didapatkan waktu median kekambuhan setelah terapi bervariasi antara 7- 36 bulan setelah terapi primer.

• Pada Follow Up dilakukan anamnesa tentang keluhan pasien, pemeriksaan fisik dan ginekologi rutin untuk mendeteksi adanya kekambuhan, efek samping terapi dan juga morbiditas psikoseksual yang mungkin terjadi. Pemeriksaan biopsi jaringan, foto thorax, USG, CT scan, MRI, PET dapat dilakukan apabila didapatkan kecurigaan kekambuhan.

1. Which human papillomavirus (HPV) subtype is associated with adenocarcinoma of the cervix?

most strongly

• a. HPV 6

• b. HPV 16

• c. HPV 18

• d. HPV 31

2. Which of the following statements regarding cervical cancer risk factors is FALSE?

• a. Cervical cancer is an acquired immune deficiency syndrome (AIDS)-defining illness.

• b. Transplant recipients have an increased risk of cervical cancer.

• c. In general, women who have an autoimmune disease and take immunosuppressant

therapy do not have an increased risk of cervical cancer.

• d. Combination oral contraceptives are associated with an increased risk of cervical cancer

due to the higher number of sexual partners in users.

• 3. Which histologic subtype of cervical carcinoma is represented in this micrograph?

Arrows point to keratin pearls.

• a. Melanoma

• b. Adenocarcinoma

• c. Squamous cell carcinoma

• d. Neuroendocrine carcinoma

4. A woman presents for a routine health maintenance visit. The following is visualized during

speculum examination. What is the most appropriate next step?

• a. Perform a Pap test

• b. Perform a cervical biopsy

• c. Refer to a gynecologic oncologist

• d. Obtain abdominopelvic computed tomography

5. What is the most appropriate surgical approach for a woman who has a stage IAI squamous

cell carcinoma of the cervix and has completed childbearing?

• a. Cold-knife conization

• b. Extra fascial hysterectomy

• c. Type III radical hysterectomy

• d. Modified ( Type II) radical hysterectomy

6. Both urinary and genital systems develop from which of the following cell types?

• a. Ectoderm

• b. Endoderm

• c. Mesoderm

• d. None of the above

7.Embryos of male or female gender are indistinguishable from each other until which number of

weeks of development?

• a. 7

• b. 10

• c. 12

• d. 14

8. During a first-trimester ultrasound or pregnancy dating, you discover that your patient has a

subseptate uterus. While counseling her, you explain that this müllerian anomaly developed in

utero secondary to failure of the midline uterine septum to reabsorb completely. Normally,

reabsorption of the uterine septum in a fetus should occur by how many weeks of gestation?

• a. 20

• b. 28

• c. 32

• d. 36

9. In the male fetus, dihydrotestosterone (DHT ) is involved in which of the following?

• a. Enlargement of the phallus

• b. Lengthening of the anogenital distance

• c. Fusion of the labioscrotal folds to form the scrotum

• d. All of the above

10. When aced with ambiguous external genitalia of a newborn at delivery, the obstetrician

should do which of the following?

• a. Examine the mother for signs of hyperandrogenism.

• b. Refer to the newborn as “your baby” and not as “it.”

• c. Refrain from gender assignment by explaining that the genitalia are incompletely formed.

• d. All of the above

11. During menopausal transition, which of the following results from cessation of ovarian steroid

hormone release?

• a. A rise in luteinizing hormone (LH) levels

• b. A rise in follicle-stimulating hormone (FSH) levels

• c. A maximal increase in the frequency and amplitude of gonadotropin-releasing hormone

secretion

• d. All of the above

12. Anovulation is the most common cause of erratic bleeding during menopausal transition.

However, as shown in this sonogram, endometrial cancer is suspected during this transition in

those with abnormal uterine bleeding (AUB). Here, the thickened heterogeneous endometrium

measures 26 mm. The overall risk for endometrial cancer increases to what percentage in women

with AUB during menopausal transition?

• a. 0.1 percent

• b. 1 percent

• c. 10 percent

• d. 30 percent

13. A 55-year-old postmenopausal, thin, patient who smokes asks for counseling regarding

osteoporosis due to her concern for future bone fracture risk. In addition to the vertebrae and

femoral neck, which of the following is most commonly fractured?

• a. Rib

• b. Wrist

• c. Fibula

• d. Humerus

14. The North American Menopause Society term genitourinary syndrome of menopause(GSM)

encompasses which of the following signs and symptoms?

• a. Dyspareunia

• b. Vulvar dryness

• c. Urinary urgency and dysuria

• d. All of the above

15. In postmenopausal women, unopposed estrogen may be derived from which of the following

sources?

• a. Exogenous estrogen

• b. Extragonadal endogenous estrogen production

• c. Decreased sex hormone-binding globulin levels

• d. All of the above

16. Which of the following regarding thyroid function is true during normal pregnancy?

• A. Foetal thyroid function is largely dependent upon the function of the maternal thyroid

• B. Plasma thyroid-binding globulin concentration increases

• C. Plasma total thyroxine concentration falls

• D. Plasma TSH concentration increases

• E. Tri-iodothyronine is not able to cross the placenta to the foetus

17. Which of the following is correct regarding the diffusion of gases through the

placental membrane?

a. 〖CO〗_2crosses the placenta from foetus to mother because of a high

concentration gradient

b. 〖CO〗_2 diffuses through the placental membrane 5 times more quickly

than O_2

c. The mean 〖PO〗_2 in the foetus is 50 mmHg

d. The mean 〖PO〗_2in the mother’s blood is approximately 30 mmHg

e. The only way the foetus can excrete 〖CO〗_2 is through the placenta

18. Which of the following is not a normal finding in a healthy pregnant patient?

• A. A fourth heart sound

• B. A raised alkaline phosphatase

• C. Tall, peaked T waves in lead III

• D. Left axis deviation on the electrocardiograph (ECG)

• E. Thrombocytopenia

19. In a normal pregnancy, which of the following is

true regarding uterine blood flow?

• A. Is about 50 mL/minute at term

• B. Is increased during uterine contractions

• C. Is reduced by prostacyclin

• D. Represents about 10% of the cardiac

output by the end of the first trimester

• E. Within the choriodecidual space is

maintained throughout the cardiac cycle

20. Which of the following is true regarding aortocaval compression in a pregnant woman?

• A. A reduction in cardiac output may be due to compression of the superior vena cava

• B. A wedge should be placed under the left side

• C. Compression of the aorta may cause uterine hypoperfusion

• D. Is greater when lying on the right side

• E. Uterine contractions reduce the cardiovascular effects of aortocaval compression

21. Regarding the human placenta, which of the

following is true?

• A. Cytotrophoblast is in direct contact with

maternal blood

• B. Decidual cells are derived from myometrial

stromal cells

• C. Each cotyledon represents a primary stem

villi

• D. The anchoring villi are attached to the

myometrium

• E. The intervillous space communicates directly

with branches of the uterine arteries

22. Which of the following is true regarding human chorionic gonadotropin?

• A. Binds to luteinising hormone (LH) receptors

• B. Has intrinsic anti-thyroid activity

• C. Is a protein molecule

• D. Is synthesised by the corpus luteum of pregnancy

• E. Secretion peaks at 20 weeks of gestation

23. The concentrations of which of the following increase during pregnancy?

• A. Albumin

• B. Sodium

• C. Fibrinogen

• D. All of the above

• E. None of the above

24. Which of the following is not true regarding trophoblast?

• A. Develops from the blastocyst

• B. Enters the maternal circulation during normal pregnancy

• C. Gives rise to the foetal blood vessels in the placenta

• D. Is genetically identical to decidua

• E. Replaces endothelium of pregnant spiral arterioles

25. Which of the following normally decreases during pregnancy?

• A. Heart rate

• B. Stroke volume

• C. Systemic vascular resistance

• D. All of the above

• E. None of the above