Download Cervical cancer

Cervical cancer
Incidence and mortality
• Worldwide, cervical cancer accounted for an estimated
530,000 new cancer cases and for 275,000 deaths
• In developed countries in 2008, cervical cancer was the
tenth most common type of cancer in women (9.0 per
100,000 women) and ranked below the top ten causes of
cancer mortality (3.2 per 100,000). In contrast, in
developing countries it was the second most common
type of cancer (17.8 per 100,000) and cause of cancer
deaths (9.8 per 100,000) among women
Histopathology:
• Squamous cell carcinoma – 69%
• Adenocarcinoma (including adenosquamous) – 25%
• Other histology (e.g. small cell carcinoma, lymphoma,
sarcoma,…etc.) – 6%
Age distribution
- The lifetime risk of developing cervical cancer for United
States women is 0.76%. The mean age at diagnosis is 48
years
Age (year)
<20
Incidence of
cervical cancer
0.1/100,000
20-24
1.5/100,000
30-85
11-15.8/100.000
Pathogenesis
• Human papillomavirus (HPV) is central to the
development of cervical neoplasia and can be detected
in 99.7% of cervical cancers.
• There are four major steps in cervical cancer
development:
1) Oncogenic HPV infection of the metaplastic epithelium
at the cervical transformation zone
2) Persistence of the HPV infection
3) Progression of a clone of epithelial cells from
persistent viral infection to precancer
4) Development of carcinoma and invasion through the
basement membrane
Pathogenesis
• Most HPV infections are transient. When HPV infection
persists, the time from initial infection to development of
high grade cervical intraepithelial neoplasia and, finally,
invasive cancer takes an average of 15 years, although
more rapid courses have been reported
• Among the more than 40 genital mucosal HPV types
identified, approximately 15 are known to be oncogenic.
Subtypes. HPV 16 and 18 are found in over 70 percent of
all cervical cancers.
Risk factors
Most of these factors are associated with an increased risk
of acquiring or having compromised immune response to
infection with human papillomavirus (HPV), the etiologic
agent of most cervical cancers. These include:
• Early onset of sexual activity
• Multiple sexual partners
• A high-risk sexual partner (e.g., a partner with multiple
sexual partners or known human papillomavirus
infection)
• History of sexually transmitted infections (e.g., Chlamydia
trachomatis, genital herpes)
• History of vulvar or vaginal squamous intraepithelial
neoplasia or cancer
Risk factors
• Immunosuppression (e.g. AIDS)
• Low socioeconomic status
• Others:
Non-white women
Early age at first birth (< 20 years old) and increasing
parity (>3 or more)
Smoking (SCC of the cervix only)
Oral contraceptive use
Cervical cancer is less common in sexual partners of
circumcised males
Routes of Spread:
Cervical cancer can spread by:
• Direct extension: may involve uterine corpus, vagina,
parametria, peritoneal cavity, bladder, or rectum.
Ovarian involvement by direct extension of cervical
cancer is rare; (0.5% in SCC and 1.7% of
adenocarcinomas)
• Lymphatic spread
• Hematogenous dissemination: the most common sites
are the lungs, liver, and bone
Clinical manifestation:
•
•
•
•
Asymptomatic – abnormal cervical smear
Vaginal bleeding
Postcoital bleeding
Abnormal vaginal discharge
In advanced disease
• Pelvic or lower back pain, which may radiate along the
posterior side of the lower extremities
• Bowel or urinary symptoms, such as pressure-related
complaints, hematuria, hematochezia, or vaginal passage
of urine or stool
FIGO staging of carcinoma of the cervix uteri
Stage 0: preinvasive carcinoma, CIS
Stage I: carcinoma strictly confined to the cervix (extension to the corpus should
be disregarded)
stage Ia - Preclinical carcinoma of the cervix, i.e. those diagnosed only by
microscopy
o Stage Ia1: lesion < 3 mm invasion & < 7 mm in width
o Stage Ia2: lesion 3-5 mm invasion & < 7 mm in width.
Stage Ib - lesion invasion > 5mm & / or diameter > 7 mm
o Stage Ib1: lesion < 4 cm
o Stage Ib2: lesion > 4 cm
Stage II: the carcinoma extend beyond the cervix but has not extend onto the
pelvic wall. The carcinoma involve the vagina, but not the lower one-third
Stage
IIa
Stage
IIb
- No obvious parametrial involvement (extension to the upper two
third of the vagina)
- Obvious parametrial involvement
Stage III: the carcinoma has extended to the pelvic wall. On rectal exam, there is no
cancer-free space between the tumor & the pelvic wall. The tumor involved the
lower third of the vagina. All cases of hydronephrosis or nonfunctioning kidney
Stage
IIIa
Stage
IIIb
- Tumor extend to the lower third of the vagina (no extension to the
pelvic wall)
- Extension onto the pelvic wall &/or hydronephrosis or non-functioning
kidney
Stage IV: the carcinoma has extended beyond the true pelvis or has clinically
involved the mucosa of the bladder or rectum.
Stage
Iva
Stage
IVb
- Spread to adjacent organs
- Spread to distant organs
Diagnosis:
Examination
• Pelvic examination – speculum, bimanual, and
rectovaginal examination for palpation and inspection
of the primary tumor, uterus, vagina, and parametria
• Examination for distant metastases – palpation of groin
and supraclavicular lymph nodes
Cervical biopsy: the diagnosis of cervical cancer is made
based upon histologic evaluation of a cervical biopsy
• Colposcopy with directed cervical biopsy
• Endocervical curettage
• Conization
Diagnosis
• Imaging studies - X rays, CT,MRI, PET…etc
• Lab: CBC,KFT, LFT, UA…etc.
Treatment
Surgical Management of Early Invasive Cancer of the
Cervix
Stage
Comment
Rx
Stage < 3 mm invasion
Conization (or)
Ia1
No lymph vascular Simple
hysterectomy
space invasion
(abdominal or vaginal)
Trachelectomy + pelvic LNDs
Stage < 3 mm invasion
(or)
Ia1
With lymph vascular Simple
hysterectomy
or
space invasion
modified radical hysterectomy
+ pelvic LNDs
Treatment
Radical trachelectomy + pelvic
Stage >3-5 mm invasion & LNDs
Ia2
<7 mm in diameter (or)
Modified radical hysterectomy
+ pelvic LNDs
Stage Lesion <2 cm
Ib1
Modified radical hysterectomy
with pelvic lymphadenectomy
Stage Lesion > 2 cm
Ib1
Radical hysterectomy with
pelvic lymphadenectomy
Complication of radical hysterectomy:
Acute / subacute Complications
• Ureterovaginal / vesicovaginal fistula (2-3%)
• Pulmonary embolus (1-2%)
• Blood loss
• Febrile morbidity (25-50%): atelectasis, pelvic cellulitis,
urinary tract infection, wound infection, pelvic abscess,
and phlebitis
• Postoperative bladder dysfunction
• Lymphocyst formation
Chronic Complications
• Bladder hypotonic
• Ureteral strictures
• Compromised sexual activity, decreased lubrication, &
shortened vagina
Treatment
For more advanced disease (> stage 1B1): Chemoradiation
Compared with surgery, chemoradiation resulted in:
• Higher incidence of sexual dysfunction
• Higher incidence of bowel dysfunction
• A higher incidence of urinary incontinence
• Ovarian failure — women treated with surgery may be at
risk for premature ovarian failure possibly due to
impairment of ovarian perfusion. Pelvic RT (with or
without concomitant chemotherapy) uniformly results in
ovarian failure due to the doses required for curative
intent therapy.
Comparison of surgery versus radiations for stage Ib / IIa
cancer of the cervix
Surgery
Radiation
Serious - Urologic fistula 3%
complicat
ions
Vagina
- Initially shortened, but
may lengthen with
regular intercourse
Ovaries
- may be conserved
Chronic
effects
- Bladder atony in 3%
- Intestinal & urologic
fistula & stricture in
1.4-5.3%
- Fibrosis & possible
stenosis particularly in
postmenopausal
women
- Destroyed
- Radiation fibrosis of
bladder & bowel in 68%
Anatomic
structure
Uterus
Simple
hysterectomy
Removed
Removed
Removed
Ovaries
Optional removal
Optional removal
Optional removal
Cervix
Removed
Removed
Removed
Vaginal margin
None
1-2 cm margin
> 2-3 cm margin
Ureters
Not mobilized
Dissected through Dissected through
broad ligament
broad ligament
Cardinal
ligaments
Divided at uterine Divided
where
border
ureter transit the
broad ligament
Divided at cervical Partially resected
border
Mobilized to base of Mobilized to upper
cervix
vagina
Not mobilized
Mobilized below
cervix
Uterosacral
ligaments
Bladder
Rectum
Modified radical
Radical
Divided at pelvic
sidewall
Divided near sacral
origin
Mobilized
to
middle vagina
Mobilized below
middle vagina
Treatment
• Women who are not surgical candidates due to
poor functional status – chemoradiation
• Women who wish to preserve fertility – For
women of reproductive age who wish to
preserve their fertility and have a lesion size ≤2
cm and no lymph node metastases
Trachelectomy +/- PLNs may be offered
Prognosis
The major prognostic factors affecting survival among
women with cervical cancer are stage, nodal status, tumor
volume, depth of cervical stromal invasion, and
lymphovascular space invasion (LVSI).
Disease stage is the most important prognostic factor
Stage
5-years Survival rate
Ia
95%
Ib
80%
II
64%
III
38%
IV
14%
Recurrent Disease
• Following treatment of early stage cervical cancer, distant
metastases or multiple recurrence sites develop in 15 to
61 percent of cases, usually within the first two years of
completing treatment.
• Recurrent cervical cancer presents as disease isolated to
the pelvis (locoregional recurrence) or with disease
involving other organs or outside the pelvis
• Treatment depends on the mode of primary therapy &
the site of the recurrence, e.g.:
Patient who have initial treatment by surgery should be
considered for radiotherapy
Patient who had radiotherapy should be considered for
surgery provided the recurrence is central & there is no
evidence of distal recurrence
Screening and Prevention
• Cervical smear: the rate of cervical cancer has declined
significantly in settings in which cervical cancer screening
is employed
• HPV vaccine