Cervical Cancer

Invasive cancer of the cervix is considered a preventable

disease
long preinvasive state
cervical cytology screening programs are
currently available
treatment of preinvasive lesions is effective

Risk factors for cervical cancer
young age at first intercourse (<16 years)
multiple sexual partners
cigarette smoking
race
high parity
lower socioeconomic status

*** Many of these risk factors are linked to sexual
activity and exposure to sexually transmitted diseases

Infection with human papillomavirus (HPV)
- causal agent in the development of cervical
cancer
- Herpes virus and Chlamydia trachomatis likely
acting as cofactors

Infection with HPV
- The initiating event in cervical dysplasia and
carcinogenesis
- high-risk subtypes: HPV 16 and 18

*** Mechanism by which HPV affects cellular growth
and differentiation is through the interaction of viral E6
and E7 proteins with tumor suppressor genes p53 and
Rb, respectively.

Human immunodeficiency virus (HIV) in cervical cancer
is thought to be mediated through immune
suppression.

Vaginal bleeding (postcoital bleeding)
- is the most common symptom occurring in
patients with cancer of the cervix.

Evaluation of the supraclavicular, axillary, and
inguinofemoral lymph nodes
- to exclude the presence of metastatic disease

Rectal examination
- is the only way to determine cervical size if the
vaginal fornices have been obliterated by
menopausal changes or by the extension of
disease.
Parametrial extension of disease is best determined by
the finding of nodularity beyond the cervix on rectal
examination

When obvious tumor growth is present, a cervical
biopsy is usually sufficient for diagnosis.

If gross disease is not present, a colposcopic
examination with cervical biopsies and endocervical
curettage is warranted.

If the diagnosis cannot be established conclusively with
colposcopy and directed biopsies, cervical conization
may be necessary.

Colposcopic examination
- is mandatory for patients with suspected early
invasive cancer based on cervical cytology and a
grossly normal-appearing cervix.
- Colposcopically directed biopsies may permit
the diagnosis of frank invasion and thus avoid
the need for diagnostic cone biopsy, allowing
treatment to be administered without delay

Colposcopic findings that suggest invasion
- abnormal blood vessels
- irregular surface contour with loss of surface
epithelium
- color tone change

Abnormal looped vessels
- are the most common colposcopic finding and
arise from the punctated and mosaic vessels
present in cervical intraepithelial neoplasia
(CIN).
- angiogenesis occurs as a result of tumor and
local tissue production of VEGF, PDGF, EGF, and
other cytokines, resulting in the proliferation of
blood vessels and neovascularization

*** Abnormal reticular vessels represent the terminal
capillaries of the cervical epithelium

Irregular Surface Contour
- The surface epithelium ulcerates as the cells
lose intercellular cohesiveness secondary to loss
of desmosomes
- also may occur as a result of papillary
characteristics of the lesion




Color tone
- may change as a result of increasing vascularity,
surface epithelial necrosis, and in some cases,
production of keratin

!!! Adenocarcinoma of the cervix does not have a
specific colposcopic appearance !!!


Histologic Appearance of Invasion

Cervical conization
- is required to assess correctly the depth and the
linear extent of involvement when
microinvasion is suspected

Early invasion
- is characterized by a protrusion of malignant
cells from the stromal epithelial junction.

Early Invasive lesions form tonguelike processes without
measurable volume and are classified as International
Federation of Gynecology and Obstetrics (FIGO) stage
Ia1.

Lesions that are smaller than 3 mm - FIGO stage Ia1

Lesions that are 3 to 5 mm or more in depth and up to 7
mm in linear extent - FIGO stage Ia2

*** The depth of invasion should be measured with a
micrometer from the base of the epithelium to the
deepest point of invasion

Depth of invasion
- is a significant predictor for the development of
pelvic lymph node metastasis and tumor
recurrence.
- lesions invade between 3 to 5 mm have positive
pelvic lymph nodes invasion
- 3 mm or less rarely metastasize

!!! Cervical cancer is a clinically staged disease !!!

FIGO staging system
- is the current standard and is applicable to all
histologic types of cervical cancer.
- When there is doubt concerning the stage to
which a cancer should be allocated, the earlier
stage should be selected.



Preinvasive Carcinoma:
Stage 0: Carcinoma in situ, intraepithelial
carcinoma

Invasive Carcinoma:
Stage Ia: Carcinoma strictly confined to the
cervix (extension to the corpus should be disregarded)
Stage Ia1 Lesions with 3 mm invasion
Stage Ia2 lesion with 3 to <5 mm depth of
invasion AND <7mm horizontal spread

Stage IB any grossly visible tumor or tumor
beyond Stage IA
Stage IB1 tumor 4 cms
Stage IB2 tumor > 4 cms

Stage II Extends beyond cervix but not to
pelvic wall; involves vagina but not the lower 1/3
Stage IIa no parametrial involvement
Stage IIA1 tumor 4 cms
Stage IIA2 tumor > 4 cms
Stage IIB with parametrial involvement

Stage IIIa involves lower third of the vagina
but no extension to pelvic wall

Stage IIIb lesion extended onto pelvic wall on
rectal exam; or (+) hydronephrosis or non-functioning
kidney

Stage IVa lesion extended onto mucosa of
bladder / rectum

Stage IVb lesion extended beyond the true
pelvis or to distant organs

A recent systematic review comparing CT scan with MRI
has shown that MRI is significantly more sensitive with
equivalent specificity
- MRI has excellent sensitivity on T2-weighted
images for the detection of parametrial disease
- MRI has become the preferred study to
evaluate tumor size, lymph node metastasis,
and local tumor extension.

Position emission tomography scans
- may be more useful than other techniques for
the detection of abdominal and extrapelvic
disease
- PET scans may be a better predictor of
treatment outcome


Radiographic guided fine-needle aspirations (FNA)
- can be performed to confirm metastatic disease
and individualize treatment planning.

*** The clinical staging system developed by FIGO is
based on the belief that cervical cancer is a local disease
until rather late in its course

PATHOLOGY

Invasive squamous cell carcinoma
- is the most common variety of invasive cancer
in the cervix
- include large cell keratinizing, large cell
nonkeratinizing, and small cell types
- Immunohistochemistry or electron microscopy
can differentiate the small cell neuroendocrine
tumors

Adenocarcinoma in situ (AIS)
- is believed to be the precursor of invasive
adenocarcinoma
- intraepithelial or invasive squamous neoplasia
occurs in 30% to 50% of cervical
adenocarcinomas
- Adenocarcinoma of the cervix is managed in the
same a manner to that used for squamous cell
carcinoma

Patients with stage I adenocarcinomas can be selected
for treatment according to the same criteria as for
those with squamous cancers

No significant difference in survival among patients
treated with radiation alone or radiation plus
extrafascial hysterectomy

About 80% of cervical adenocarcinomas are made up
predominantly of cells of the endocervical type with
mucin production.

Minimal deviation adenocarcinoma (adenoma
malignum)
- is an extremely well-differentiated form of
adenocarcinoma in which the branching
glandular pattern strongly simulates that of the
normal endocervical glands
- lining cells have abundant mucinous cytoplasm
and uniform nuclei

Adenosquamous carcinomas
- Carcinomas with a mixture of malignant
glandular and squamous components
- have a poorer prognosis than those with pure
adenocarcinoma or squamous carcinoma
- Glassy cell carcinoma has been recognized as a
poorly differentiated form of adenosquamous
carcinoma

Embryonal rhabdomyosarcoma
- most important sarcoma of the cervix
- occurs in children and young adults
- has grapelike polypoid nodules, known as
botryoid sarcoma

Cervical adenosarcoma
- low-grade tumor with a good prognosis

Cancer of the cervix spreads by:
- direct invasion into the cervical stroma, corpus,
vagina, and parametrium
- lymphatic metastasis
- blood-borne metastasis
- intraperitoneal implantation

The cervix is commonly involved in cancer of the
endometrium and vagina

Cervical primaries
- Most lesions that involve the cervix and vagina

Treatment Options

*** The treatment of cervical cancer is similar to the
treatment of any other type of malignancy in that both
the primary lesion and potential sites of spread should
be evaluated and treated

Radiation therapy can be used in all stages of disease

Surgery is limited to patients with stage I to IIa disease

5-year survival rate for stage I cancer of the cervix is
approximately 85% with either radiation therapy or
radical hysterectomy.

Surgery
- There are advantages to the use of surgery
instead of radiotherapy, particularly in younger
women for whom conservation of the ovaries is
important
- are easily repaired and without long-term
complications
- Sexual dysfunction is less likely to occur after
surgical therapy than radiation because of
vaginal shortening, fibrosis, and atrophy of the
epithelium associated with radiation.

Radical hysterectomy
- is reserved for women who are in good physical
condition

Generally, it is prudent not to operate on lesions that
are larger than 4 cm in diameter because these patients
will require postoperative radiation therapy.

If radiation therapy is needed, ovarian function may be
preserved by transposing the ovaries out of the
planned radiation field

Cone biopsy of the cervix
- serves both a diagnostic and therapeutic role in
cervical cancer
- is indicated to confirm the diagnosis of cancer,
as well as to definitively treat stage Ia1 disease
when preservation of fertility is desired
- effective treatment:
o no evidence of lymphvascular space
invasion
o both endocervical margins and
curettage findings must be negative for
cancer or dysplasia.

Simple (Extrafascial) Hysterectomy
- Type I hysterectomy is an appropriate therapy
for patients with stage Ia1 tumors without
lymph-vascular space invasion who are not
desirous of future fertility. (lymphadenectomy
is not recommended)

If lympha-vascular space invasion is found, a modified
radical hysterectomy with pelvic lymphadenectomy is
appropriate and effective therapy.

Radical trachelectomy
- is a procedure that is gaining popularity as a
surgical management option for women with
stage 1a2 and Ib1 disease who desire uterine
preservation and fertility.
- may be performed vaginally or abdominally
- it usually is accompanied by pelvic
lymphadenectomy and cervical cerclage
placement
- Patients who are ideal candidates for this
procedure have
o tumors less than 2 cm in diameter
o negative lymph nodes
o no lymphvascular space
involvement.

Radical hysterectomy
- The operation includes pelvic lymph node
dissection along with removal of most of the
uterosacral and cardinal ligaments and the
upper one third of the vagina.
- This operation has been referred to as the type
III radical hysterectomy

Hysterectomy (by Wertheim)
- is less extensive than a radical hysterectomy
and removes the medial half of the cardinal
and uterosacral ligaments
- This procedure is often referred to as the
modified radical or type II hysterectomy


The modified radical hysterectomy (type II) differs
from the radical hysterectomy (type III) in the
following ways:
- The uterine artery is transected at the level of
the ureter, thus preserving the ureteral branch
to the ureter.
- The cardinal ligament is not divided near the
sidewall but instead is divided at about its
midportion near the ureteral dissection
- The anterior vesicouterine ligament is divided,
but the posterior vesicouterine ligament is
conserved
- smaller margin of vagina is removed

Type IV operation
- the periureteral tissue, superior vesicle artery,
and as much as three fourths of the vagina are
removed

Type V operation
- portions of the distal ureter and bladder are
resected.

The paravesical space is bordered by the following
structures:
- The obliterated umbilical artery running along
the bladder medially
- The obturator internus muscle along the pelvic
sidewall laterally
- The cardinal ligament posteriorly
- The pubic symphysis anteriorly


The pararectal space is bordered by the following
structures:
- The rectum medially
- The cardinal ligament anteriorly
- The hypogastric artery laterally
- The sacrum posteriorly