Download Management of Cervical Cancer

Management of Cervical
Cancer
Chu-Ling Wang
4/19/2006
Outline
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Epidemiology
Risk factors of cervical cancer
Role of human papillomavirus
Clinical manifestations
Management of cervical cancer
Human papillomavirus vaccine
Cervical cancer
• In the United States
– 10,370 new cases are diagnosed annually
– 3,710 deaths (1.3% of cancer deaths in women)
• Incidence
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Mean age at diagnosis of 47 years
0/100,000/year in women under age 20
1.7/100,000/year in women aged 20 - 24 years
Peaking at 16.5/100,000/year in women aged 45 to 49
years
– Only 10% of cases occurred in women age 75 or more
Cervical cancer
• In Taiwan (2002)
– 5,725 new cases are diagnosed (8.98% of cancer)
– 941 deaths (2.74% of cancer deaths)
• Incidence
– Mean age at diagnosis of 49 years
Risk factors of cervical cancer
• Early onset of sexual activity
• Multiple sexual partners
• High-risk sexual partner
– eg, promiscuous sexual activity, sexual exposure to a
partner with human papillomavirus infection
• Other risk factors:
– History of sexually transmitted diseases (eg, herpes
simplex virus)
– Smoking, immunosuppression, low socioeconomic
status, and previous history of vulvar or vaginal
squamous dysplasia
Role of human papillomavirus
• The human papillomavirus (HPV) is central to the
development of cervical neoplasia and can be
detected in almost all cervical cancers.
• Most HPV infections are transient, not all HPVs
are oncogenic, and the virus alone is not
sufficient to cause cervical neoplasia.
• The most prevalent HPV types associated with
cervical cancer are HPV-16 (60%) and HPV-18
(10%).
Histopathology
• Squamous cell carcinomas (SCCs) : 80%
• Adenocarcinomas: 15 %
• Adenosquamous carcinomas : 3 to 5 %
• Adenocarcinoma:
– A stronger association with oral contraceptives than
does squamous cell cancer. [Cancer J 2003 Sep-Oct;9(5):348-59 ]
– The risk increases with increasing duration of oral
contraceptive use.
Clinical manifestations
• Early cervical cancer is frequently asymptomatic,
underscoring the importance of screening.
• The most common symptoms at presentation are:
– Abnormal vaginal bleeding
– Postcoital bleeding
– Vaginal discharge that may be watery, mucoid, or
purulent and malodorous
• Advance disease:
– Pelvic or lower back pain
– Bowel or urinary symptoms, such as hematuria
Tests for screening for cervical
cancer
• There are two types of
technologies now available:
cervical
cytology
– The conventional Pap Smear
– The newer thin layer liquid preparations (eg,
ThinPrep®):
This newer technique reduces the false negative rate
of a conventional Pap smear by 60 % (ie, from 15-20
to 6-9 false negatives per 100 smears on initial
screening)
• Human papillomavirus testing
– A combined test (HPV plus Pap smear) was approved
for primary screening by the FDA in April 2003.
Human papillomavirus testing
• A combination of HPV DNA testing and cervical
cytology in women over age 30 who are being
screened for cervical cancer is another option for
primary screening.
• The rationale is to take advantage of the high
sensitivity of HPV DNA testing and the high
specificity of cervical cytology to increase the
screening interval in women who test negative for
HPV DNA and negative for cytological
abnormalities.
Examinations
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Palpation and inspection of the primary tumor
Colposcopy (陰道鏡檢查)
Endocervical curettage (子宮內頸搔刮術)
Conization (錐狀切片)
Hysteroscopy (子宮腔鏡)
Cystoscopy (膀胱鏡)
Proctoscopy (直腸鏡)
Intravenous pyelogram (IVP) (靜脈腎盂攝影)
Radiography of the lungs and skeleton
The International Federation of Gynecologists
and Obstetricians (FIGO) Staging System
FIGO Stage
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0 : Carcinoma in situ
IA : Microinvasive (IA1, IA2)
IB : Invasive (>5mm FIGO)
IIA : Upper 2/3 of vagina
IIB : Parametrial involvement
IIIA: Involves lower 1/3 of vagina
IIIB: Extends to pelvic and/or caused
hydronephrosis/ nonfunctional kidney
• IVA: Spread to bladder or rectum
• IVB: Distant metastasis
FIGO Stage (Con’t.)
Optional evaluation procedures
• Although they are not used to assign disease
stage in the FIGO classification, optional staging
examinations,
including
CT,
MRI,
PET,
lymphangiography (LAG), or ultrasonography
may be of value for planning treatment,
particularly the extent of the radiation therapy
field or scope of surgery.
MRI vs. CT
• Detection of nodal disease
– Sensitivity: MRI 60% vs. CT 43%
• Detection of parametrial invasion
– Sensitivity: MRI 74% vs. CT 55%
– MRI showed a trend toward better assessment of
bladder and rectal involvement.
• Positive findings by either imaging modality
should be histologically confirmed by fine needle
aspiration under CT guidance.
Gynecol Oncol 2003 Oct;91(1):59-66.
PET scan
• PET scanning may provide a better assessment
of the presence of extrapelvic metastases than
other imaging modalities.
Management of cervical cancer
Early stage (FIGO stage IA, IB1, nonbulky IIA)
• Radical Hysterectomy or radiation therapy
– The survival is similar with radical hysterectomy or
radiation therapy.
– Surgery may preserve ovarian function and long-term
sexual function, providing an advantage in
premenopausal patients.
– Radical trachelectomy with lymphadenectomy is an
alternative to radical hysterectomy for selected
women with early stage lesions who wish to preserve
fertility.
Management of cervical cancer
Early stage (FIGO stage IA, IB1, nonbulky IIA)
• Radiation therapy
– Normal ovarian function may be preserved in only 20
to 50% of premenopausal women who receive
postoperative adjuvant RT.
– The two main methods of radiation delivery for
cervical cancer are external photon beam RT and
brachytherapy.
– Several isotopes are available for intracavitary
brachytherapy:
Low dose rate therapy, typically with 137-Cs.
High dose rate therapy, typically with 192-Ir.
Management of cervical cancer
Early stage (FIGO stage IA, IB1, nonbulky IIA)
• For women who undergo hysterectomy, the
presence of positive or close resection margins,
positive
lymph
nodes,
or
microscopic
parametrial involvement indicates a high risk for
recurrence.
– Recommend
postoperative
cisplatin-based
concomitant chemoradiotherapy rather than adjuvant
RT alone.
– Weekly cisplatin (40 mg/m2 to a cumulative dose of at
least 200 mg/m2) during RT.
Management of cervical cancer
Early stage (FIGO stage IA, IB1, nonbulky IIA)
• Compared to RT alone, chemoradiotherapy was
associated with a significant 29% reduction in
the risk of death [absolute improvement in
overall survival of 12 % (from 40 to 52%)]; and a
39% improvement in PFS [16% absolute
improvement (from 47 to 63%)].
• Concomitant chemoradiotherapy was associated
with a significant decrease in both local and
distant recurrence compared with RT alone.
Lancet 2001 Sep 8;358(9284):781-6.
Quality of Life
• Quality of life after RT or surgery:
– Both hysterectomy and RT can lead to changes such
as vaginal shortening and decreased vaginal
lubrication, which adversely influence sexual function,
overall quality of life.
Quality of Life (Con’t.)
• Women were at least 5 years after initial
treatment for cervical cancer. Eligible women had
squamous cell tumors smaller than 6 cm (stage I)
at diagnosis, were currently disease-free, and
had either undergone surgery or radiotherapy, but
not both.
• 114 patients (37 surgery, 37 radiotherapy, 40
controls) were included for analysis.
J Clin Oncol 23:7428-7436.
Quality of Life (Con’t.)
• Cervical cancer survivors treated primarily with
radical
hysterectomy
have
less
sexual
dysfunction
than
patients
treated
with
radiotherapy.
• Authors strongly recommend either the use of a
vaginal dilator or the engagement in sexual
intercourse frequently after completion of
radiotherapy for cervical cancer in an effort to
maintain the length, width, and elasticity of the
vaginal canal.
J Clin Oncol 23:7428-7436.
Management of cervical cancer
Bulky stage IB2 and IIA disease
• Women with bulky early stage cervical cancer (ie,
stage IB2 and IIA) have a higher local failure
rate. After surgery alone, the rate of relapse is as
high as 30%.
Management of cervical cancer
Bulky stage IB2 and IIA disease
• There are three options for treating women with
stage IB2 or IIA disease:
1. Chemoradiotherapy alone
2. Surgery followed by chemoradiotherapy
– For patient with high or intermediate risk factors for
recurrence
3. Chemoradiotherapy followed by hysterectomy
– Reduction in pelvic recurrence rates (from 15 to 20 %
to 2 to 5%)
Clinical practice guideline
Management of cervical cancer
Locally advanced disease
• For women with stages IIB, III, and IVA cervical
SCC,
primary
chemoradiotherapy
is
recommended over RT alone.
• Suggest weekly cisplatin (40 mg/m2 to a
cumulative dose of at least 200 mg/m2) during
RT.
Management of cervical cancer
Locally advanced disease
• The previously meta-analysis included trials that
randomly assigned patients with FIGO stage IB to
IVA disease to concomitant chemoradiotherapy
vs. RT with or without surgery, and with or without
additional adjuvant chemotherapy
• Compared
to
RT
alone,
concomitant
chemoradiotherapy was associated with a
significant 29% reduction in the risk of death, a
39% improvement in PFS, and a significant
decrease in both local and distant recurrence.
Lancet 2001 Sep 8;358(9284):781-6.
Clinical practice guideline
HPV Vaccine
• A randomised, double-blind, controlled trial to
assess the efficacy, safety, and immunogenicity
of a bivalent HPV-16/18 L1 virus-like particle
vaccine.
• 1113 women between 15–25 years of age to
receive three doses of either the vaccine
formulated with AS04 adjuvant or placebo on a 0
month, 1 month, and 6 month schedule. (followup 27 months)
Lancet 2004; 364: 1757–65
HPV Vaccine (Con’t.)
• In the according-to-protocol analyses:
– Vaccine efficacy was 91.6% against incident infection
and 100% against persistent infection with HPV-16/18.
• In the intention-to-treat analyses:
– vaccine efficacy was 95.1% against persistent cervical
infection with HPV-16/18 and 92.9% against cytological
abnormalities associated with HPV-16/18 infection.
Lancet 2004; 364: 1757–65
HPV Vaccine (Con’t.)
• The vaccine targets HPV types 16 and 18.
Women were followed for up to 4.5 years:
– More than 98% of women had antibodies against
HPV16 and HPV18.
– Vaccine efficacy was 97% against incident infection
with HPV-16/18.
– Protection against HPV16- or HPV18-related
precancerous changes to the cervix was 100%.
Lancet. Early Online Publication April 6, 2006.
HPV Vaccine (Con’t.)
• A randomised double-blind placebo-controlled
phase II trial was done to assess the efficacy of a
prophylactic quadrivalent vaccine targeting the
HPV types associated with 70% of cervical
cancers (HPV 16 and 18) and with 90% of genital
warts (HPV 6 and 11).
• Women between 16–23 years of age to receive
three doses of HPV vaccine (n=277) or placebo
(n= 275) on a day 1, month 1, and month 6.
(follow-up 36 months)
Lancet Oncology 2005; 6: 271–278
HPV Vaccine (Con’t.)
• Combined incidence of persistent infection or
disease with HPV 6, 11, 16, or 18 fell by 90%
( p<0.0001) in those assigned vaccine compared
with those assigned placebo.
Lancet Oncology 2005; 6: 271–278