KANKER SERVIKS

Induksi Senior Patol

Obstetri 2016

PENDAHULUAN
Kanker serviks merupakan kanker genital
wanita yang paling umum, setiap tahun
sekitar 500.000 wanita menderita kanker
serviks dan 75% berasal dari negara
berkembang.

300.000 wanita meninggal setiap

tahunnya karena kanker serviks, 75%
berasal dari negara berkembang.

INSIDEN
Angka kejadian 4-6% dari kanker
genital wanita.

Paling banyak terjadi pada usia 4050 tahun.

PENGERTIAN
Kanker serviks adalah penyakit ganas
pada seriks uterus yang disebabkan
oleh infeksi Human Papilloma Virus
(HPV) grup onkogenik resiko tinggi,
terutama HPV 16 dan 18 serta
filogeniknya.
Lebih dari 95% kanker serviks adalah
tipe epithelial yang terdiri dari jenis
karsinoma sel skuamosa dan
adenokarsinoma.

Faktor Resiko dan Etiologi

Hubungan seksual sebelum usia 16 th
meningkatkan resiko 50%
Multiseksual partner
Merokok
Male related risk factors :
Number of the partners previous sexual relationships is relevant .
Cervical cancer risk increased if partners has penile cancer
Previous wife with cervical cancer.

Previous CIN

Faktor Resiko dan Etiologi

Poor uptake of screening program.
Long term use of the contraceptive pill increase the
risk due to increasing exposure to seminal fluids.
Barrier method decrease the risk (condom)
Immuno suppresion risk increased with immuno
suppressed renal transplant patients and in HIV
positive women.
HPV (Human papilloma virus ) infection mainly
16,18
the main aetiological is infection with subtypes of HPV (16,18)
Low socioecomic class

HPV 16,18

Smoking

Cervical cell

Male factors

Infhibation of CX
cellp53 tumour
suppression gyne
Protection against
tumour
development lifted

Cancer develops

Type of Patient
Multiparo
us

Low
socioecon
omic class

Poor
hygiene

Prostitute
s

Predisposing Factors
Cervical dysplasia

Cervical intraepithelial
neoplasia
CIN III / CARCINOMA IN
SITU
THE LESION PROCEEDS THE
INVASION BY 10-12 YEARS

GEJALA KLINIS
Early symptoms
- None.
- Thin, watery, blood
tinged vaginal
discharge frequently
goes unrecognized by
the patient.
- Abnormal vaginal
bleeding
Intermenstrual
Postcoital
Perimenopausal
Postmenopausal
- Blood stained foul
vaginal discharge.

Late symptoms
Pain, leg oedema.
Urinary and rectal
symptoms
Dysuria
Haematuria
Rectal bleeding
Constipation
Haemorrhoids
Uraemia

Tipe PA

Squamous cell carcinoma (90%)

Adenocarcinoma (10%)

Tipe Pertumbuhan
Kanker
Exophytic
is like
cauliflow
er filling
up the
vaginal
vault

Endophyti
c
it
appears
as hard
mass
with a
good
deal of
induratio
n

Ulcerative
an ulcer
in the
cervix

DIAGNOSIS
Anamnesis

Biasanya asimptomatik
Perdarahan vagina
Inter Menstrual bleeding
Post coital bleeding
Perimenopausal bleeding
Postmenopausal bleeding
Blood stain vaginal discharge

DIAGNOSIS
PEMERIKSAAN

Inspeksi
Palpasi
Biopsi
Sistoskopi
Rektoskopi
IVP
Foto thorak
USG
CT scan
MRI

Cytology

Histology

Colposcopy

Penentuan Stadium
Berdasarkan kriteria FIGO 2009
Pemeriksaan bisa dengan anesthesi
Bimanual palpation
Cervical biopsy, uterine biopsy
Cystoscopy, Proctoscopy, if
necessary

FIGO staging system, 2009

Stage I
The carcinoma is strictly confined to the cervix
(extension to the corpus would be disregarded)
Stage IA: Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion 5 mm and largest extension 7 mm
Stage IA1: Measured stromal invasion of 3.0 mm in depth and extension of 7.0 mm.
Stage IA2: Measured stromal invasion of >3.0 mm and 5.0 mm with an extension of not >7.0 mm
Stage IB: Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA *
Stage IB1: Clinically visible lesion 4.0 cm in greatest dimension
Stage IB2: Clinically visible lesion >4.0 cm in greatest dimension

Stage II
Cevical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina
Stage IIA: Without parametrial invasion
Stage IIA1: Clinically visible lesion 4.0 cm in greatest dimension
Stage IIA2: Clinically visible lesion >4 cm in greatest dimension
Stage IIB: With obvious parametrial invasion

Stage III
The tumor extends to the pelvic wall and/or involves lower third of the vagina and or causes hydronephrosis or non-functioning kidney **
Stage IIIA: Tumor involves lower third of the vagina, with no extension to the pelvic wall
Stage IIIB: Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney

Stage IV
The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum.
A bullous edema, as such, does not permit a case to be allotted to Stage IV
Stage IVA: Spread of the growth to adjacent organs.
Stage IVB: Spread to distant organs.
All macroscopically visible lesionseven with superficial invasionare allotted to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 mm and a horizontal
extension of not >7.00 mm. Depth of invasion should not be >5.00 mm taken from the base of the epithelium of the original tissuesuperficial or glandular. The depth of invasion should always be reported in
mm, even in those cases with early (minimal) stromal invasion (~1 mm). The involvement of vascular/lymphatic spaces should not change the stage allotment.
**
On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. All cases with hydronephrosis or non-functioning kidney are included, unless they are known to be due to
another cause.
*

PENYEBARAN
Direct

Lymphatic

- Uterus

A- primary node:
parametrial.
- Vagina
Paracervical.
- Parametrium
Vesicovaginal.
- Bladder and rectum Rectovaginal.
Hypogastric.
Obturator and external
iliac
B-Secondary nodes:
Common iliac
Sacral
Vaginal
Paraaortic
Inguinal.

Dissemination
(late)
- parametrial spread
causes obstruction of
the ureters, many
deaths occur due to
uraemia.
- Obstruction to the
cervical canal results in
pyometria.

DIAGNOSA BANDING
Kanker endometrium (terutama
stadium II)
Servisitis kronis
Cervical ectropion
Cervical tuberculosis
Cervical syphilis, Schistosomiasis,
and Choriocarcinoma are rare
causes

TERAPI

Surgical.
Radiotherapy.
Radiotherapy & Surgery.
Radiotherapy and Chemotherapy
followed by Surgery.
Palliative treatment.

Cervical cancer
FIGO Stage I a
Microinvasive carcinoma (invasion 5 mm)
Recommended work-up
Vaginal and rectal examination, exfoliative cytology (Papanicolaou smear), colposcopy, biopsy and/or endocervical curettage (ECC), conization or Loop electrosurgical procedure (LEEP)
Histopathological finding with all standard tumor parameters
Laboratory analyses: WBC, biochemical analyses
Imaging: Chest X-ray, pelvic and abdominal ulstrasound

Diagnosis is based on conization!

Conization

Necessary HP parameters:2

Depth of invasion

Width of the tumor

Tumor differentiaion

Lympho-vascular space invasion (LVSI)

Resection margins

Margins
Margins clear
clear
ECC
ECC negative
negative

Stage
Stage Ia1
Ia1
LVSI
LVSI negative
negative

Conization if preservation of fertility is desired

or
Simple (extrafascial, type A6) hysterectomy with or without
salpingoophorectomy

Margins
Margins and/or
and/or
ECC
positive
ECC positive for
for dysplasia
dysplasia

Stage
Stage Ia1
Ia1 with
with extensive
extensive LVSI
LVSI
Stage
Stage Ia2
Ia2

Repeated conisation
Modified radical hysterectomy (type B6) if re-conisation is not possible
pelvic lymphadenectomy

Conization or radical trachelectomy if preservation of fertility is desired

or
Modified radical hysterectomy (type B6)
and
Pelvic lymphadenectomy

Recommended follow-up
Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination, including cytology
colposcopy, should be performed depending on symptoms, local findings and general condition of the patient

and

Cervical cancer
FIGO Stage Ib - IIa
Squamocellular, Adenocarcinoma, Adenosquamous

Recommended work-up

Neccessary investigations:
Vaginal and rectal examination, colposcopy, biopsy and/or endocervical curettage (ECC); conization or loop electrosurgical procedure (LEEP) if needed for definitive diagnosis
Histopathological finding with all standard tumor parameters
Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb
Imaging: Chest X-ray, abdominal and pelvic ultrasound (size and position of the tumor and tumor volume/cervix ratio)
Optional investigations:
Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should be confimed histologically

Radical surgery

Chemo-radiation

or

Neoadjuvant chemotherapy followed by radiation or surgery is an option for locally advanced

tumors (Ib2 and IIa2) but awaits confirmatory evidence from controlled clinical trials.

Medical contra-indications for surgery

Ib2/IIa2 tumors in selected cases
Anterior vaginal extension
Invasive cancer after simple hysterectomy
Choice of the patient

Uterus with paracervical tissues and upper part of vagina (radical, type C6 hysterectomy) + pelvic lymphadenectomy
or
Entire cervix with paracervical tissues (radical trachelectomy) if fertility is desired + pelvic lymphadenectomy
or
Upper part of vaginal cuf, paracervical tissues + pelvic lymphnodes in case of previous simple hysterectomy
* At least 2 cm distance from the resection margins is desirable
** In premenopausal women ovaries can be retained; if so tranposition is advised.
*** For the desision of further management, all neccesary histopathologic parameters44 should be requested

Negative
Negative nodes
nodes
GOG
GOG score*
score*
5
*consider
*consider using
using GOG
GOG score
score as
as aa guide
guide for
for adjuvant
adjuvant treatment
treatment5
Low
Low risk
risk
(GOG
(GOG score
score << 120)
120)

Low
Low risk
risk
(GOG
(GOG score
score << 120)
120)

Follow up

Radiation
Chemotherapy

Positive
Positive nodes
nodes (1-3)
(1-3)
Poorly
Poorly differentiated
differentiated or
or undifferentiated
undifferentiated tumor
tumor (G3)
(G3)
LVSI
LVSI present
present
Primary
Primary tumor
tumor
(tumor-cervix
(tumor-cervix volume)
volume) >3
>3 cm
cm
Endocervical
Endocervical invasion
invasion
(barrel
(barrel shaped
shaped cervix)
cervix)
Inadequate
Inadequate surgery
surgery
Insufficient
Insufficient HP
HP (if
(if report
report of
of all
all necessary
necessary parts
parts is
is missing)
missing)

Radiation
Chemotherapy

Positive
Positive resection
resection margins
margins
Involvement
Involvement of
of parametria
parametria
Residual
Residual tumor
tumor
Multiple
Multiple positive
positive nodes
nodes (>3)
(>3)

Concomitant
Chemo-radiation

Recommended follow-up
Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination should be performed
depending on symptoms, local findings and general condition of the patient

Cervical cancer
FIGO stage IIb- IV
Recommended work-up

Vaginal and rectal examination, biopsy or endocervical curettage (ECC)

Histopathological finding with all standard tumor parameters
Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb
Imaging: Chest X-ray, abdominal and pelvic ultrasound
Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should
be confimed histologically

Pelvic MRI and

Abdominal CT
Paraaortic
Paraaortic nodes
nodes (PALN)
(PALN) negative
negative
(=not
(=not enlarged)
enlarged)

Pelvic
Pelvic or
or paraaortic
paraaortic nodes
nodes (PALN)
(PALN)
positive
positive (enlarged
(enlarged 2
2 cm))
cm))

Pelvic ( paraaortic) radiation

+ brachytherapy
+ concomitant chemotherapy

CT of the lungs & mediastinum

CT
CT negative
negative

Pelvic radiation (with paraaortic if PALN are positive) + brachytherapy + concomitant chemotherapy
* Consider:
resection of adnexal mass and/or extraperitoneal resection of enlarged nodes
Sequential chemoth and Concomitant ChemoRadioTherapy /External Beam RadioTherapy (CCRT/EBRT)

CT
CT positive
positive

Palliative pelvic RT
Palliative chemotherapy

*Stage IVa

with vesicovaginal fistula: if pelvic, abdominal and chest imaging exclude distant metastases primary pelvic exenteration can be considered
NACT may be offered to large bulky tumors to downsize tumor prior to CCRT

Recommended follow-up
Every 3 months after completed therapy; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination should be performed depending on
local findings and general condition of the patient

symptoms,

Cervical cancer
Squamocellular, Adenocarcinoma,
Adenosquamous

Recommended work-up

Neccessary investigations:
Vaginal and rectal examination, colposcopy, biopsy and/or endocervical curettage (ECC); conization or loop electrosurgical procedure (LEEP) if needed for definitive diagnosis
Histopathological finding with all standard tumor parameters
Laboratory analyses: WBC, biochemical analyses including including check for renal function and Hb
Imaging: Chest X-ray, abdominal and pelvic ultrasound (size and position of the tumor and tumor volume/cervix ratio)
Optional investigations:
Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should be confirmed histologically
*Stage of the disease is determined using FIGO classification1

FIGO Ia

FIGO Ib-IIa

Diagnosis is based on conization;

resection margins should be clear
Further decision depends on the
presence of poor histologic prognostic
factors2

FIGO
FIGO Ia1
Ia1
LVSI
LVSI negative
negative

FIGO
FIGO Ia1,
Ia1, LVSI
LVSI
positive
positive

Conization
or
Simple hysterectomy
(type A66)

Conization/radical
trachelectomy
or
Modified radical
hysterectomy(type B66)
and
Pelvic Lymphadenectomy

Follow-up

Surgery

or

FIGO IIb-IV
Chemo-radiation

Medical contra-indications for surgery

Ib2/IIa tumors
Anterior vaginal extension
Invasive cancer after simple hysterectomy
Choice of the patient
Radical hysterectomy (type C6)
or
Radical trachelectomy
or
Resection of the upper part of vagina and parametrectomy in case of previous
simple hysterectomy
and
Pelvic lymphadenectomy
* Decision about further therapy is based on the presence of adverse histological
factors
No
No adverse
adverse prognostic
prognostic factors
factors
Follow-up

Concomitant chemoradiation
or
Radical radiation only if unfit for
chemotherapy
* Stage IV1 with vesicovaginal fistula: if
pelvic, abdominal and chest CT exclude
distant metastases, primary pelvic
exenteration can be considered

Neoadjuvant chemotherapy followed by radiation

or surgery is an option for locally advanced
tumors, but awaits confirmatory evidence from
controlled clinical trials.

4
Adverse
Adverse prognostic
prognostic factors
factors4 present
present

Adjuvant therapy
(Radiation Chemotherapy)

Recommended follow-up
Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination
should be performed depending on symptoms, local findings and general condition of the patient

Pilihan Terapi tergantung

Kondisi Pasien

Keadaan umum pasien

Usia pasien
Stadium penyakit
Tipe lesi
Ketersediaan ahli

Surgical Procedure
The classic surgical procedure is the
wertheims hystrectomy for stage
Ib,IIa, and some cases of IIb in young
and fat patient

Werthemeims
Hystrectomy
Total abdominal hystrectomy including
the parametrium.
Pelvic lymphadenectomy
3 cm vaginal cuf
The original operation conserved the
ovaries, since squamouss cell carcinoma
does not spread directly to the ovaries.
Oophorectomy should be performed in
cases of adenocarcinoma as there is 510% of ovarian metastasis

Keuntungan Terapi Bedah

It allows presentation of the ovaries
(radiotherapy will destroy them)
There is better chance of preserving
sexual function
Vaginal stenosis occurs in up 85% of
irradiates
Psychological feeling of removing the
disease from the body
More accurate staging and prognosis

KOMPLIKASI TINDAKAN BEDAH

Perdarahan : primary or secondary

Cedera pada kandung kemih, ureter
Disfungsi kandung kemih
Fistula
Lymphocele
Pemendekan vagina

Radiotherapy

Stage IIb and III

Radical Radiotherapy
External irradiation (Teletherapy)
Intracavitary radiation
(Brachytherapy)
In some cases of stage IIa or b radio
and chemotherapy to be given then
followed by simple hysterectomy

Palliative Therapy

For stage IV individualized therapy

Some suitable for palliative XRT ( usually
intracavitary Caesium)
Some suitable for extensive surgery
Some suitable for chemotherapy
Good nursing care
Analgesia-must be used in sufficient amount to
alleviate pain (Codein sulfate, Pethidine,
Morphine, Diamorphine)
Antiemetic if necessary
IV drip, enteral, and parentral feeding
Urinary Catheterization
Other measures for symptom relief

PROGNOSIS
Tergantung pada :

Usia pasien

Keadaan umum pasien

Stadium penyakit

Tipe tumor

Adekuatnya terapi

5 YEARS SURVIVAL FOLLOWING

THERAPY :
Stage I -------80%
Stage II-------50-60%
Stage III-------30-40%
Stage IV-------4%

MANAGEMENT OF RECURRENT
DISEASE
1. Local recurrence
Radiation if not used
Pelvic exenturation
2. Distant disease
Chemotherapy

Cervical cancer
- recurrence Recommended work-up

Vaginal and rectal examination, biopsy - histopathological confirmation of recurrence

Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb
Imaging: Chest X-ray, pelvic and abdominal ultrasound, pelvic NMR and CT of the lungs and abdomen; (PET/CT if possible)
Cystoscopy, rectoscopy, IVU or sonographic renal examination

Lungs & abdominal CT

Pelvic
Pelvic recurrence
recurrence

No previous radiation

Options include:
Chemo-radiation
Neoadjuvant chemotherapy (NACT)
Supportive care

Extrapelvic
Extrapelvic recurrence
recurrence

Previous radiation

Central
Central pelvic
pelvic
recurrence
recurrence

Options include
Radical hysterectomy in tumor <2 cm
Pelvic exenteration
Neoadjuvant chemotherapy (NACT) + surgery
Other options if surgery is not possible:
Re-irradiation
Neoadjuvant chemotherapy (NACT) + radiation
Systemic therapy
Supportive care

Sidewall
Sidewall pelvic
pelvic
recurrence
recurrence

Options include:
Palliative radiotherapy or chemo-radiation
Systemic therapy
Supportive care
* Resection in selected cases
(in particular paraaortic nodes)
may be considered

Options include:
Resection of isolated disease
Systemic therapy
Supportive care

Recommended follow-up
Every 3 months for two years or more often if clinically indicated. Every 4-6 months thereafter. Annually afterwards. Investigations in addition to gynaecological examination should be
depending on symptoms, local findings and general condition of the patient

performed

Follow Up