The Management of
Cervical , Vulvar and
Vaginal Cancers
Kerry J. Rodabaugh, M.D.
Division of Gynecologic Oncology
University of Nebraska Medical Center
Incidence:
global public health issue
450,000 – 500,000 women diagnosed each
year worldwide
In developing countries, it is the most
common cause of cancer death
340,000 deaths in 1985
United States Incidence
15,000 women diagnosed annually
4,800 annual deaths
Mortality Rates
• <2/100,000: Finland, France, Greece,
Israel, Japan, Korea, Spain, Thailand
• 2.7/100,000: USA
• 12-15.9/100,000: Chile, Costa Rica,
Mexico
Lifetime risk of developing
cervical cancer
5% - South America
0.7% - USA
Cervical CA Risk Factors
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Early age of intercourse
Number of sexual partners
Smoking
Lower socioeconomic status
High-risk male partner
Other sexually transmitted diseases
Up to 70% of the U.S. population is infected with
HPV
Screening Guidelines for the Early
Detection of Cervical Cancer,
American Cancer Society 2003
• Screening should begin approximately three years after a women
begins having vaginal intercourse, but no later than 21 years of
age.
• Screening should be done every year with regular Pap tests or
every two years using liquid-based tests.
• At or after age 30, women who have had three normal test results
in a row may get screened every 2-3 years. However, doctors may
suggest a woman get screened more if she has certain risk factors,
such as HIV infection or a weakened immune system.
• Women 70 and older who have had three or more consecutive Pap
tests in the last ten years may choose to stop cervical cancer
screening.
• Screening after a total hysterectomy (with removal of the cervix) is
not necessary unless the surgery was done as a treatment for
cervical cancer.
American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005
Pap Smear
• Single Pap false negative rate is 20%.
• The latency period from dysplasia to
cancer of the cervix is variable.
• 50% of women with cervical cancer have
never had a Pap smear.
• 25% of cases and 41% of deaths occur in
women 65 years of age or older.
Clinical Presentation
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CIN/CIS/ACIS – asymptomatic
Irregular vaginal bleeding
Vaginal discharge
Pelvic pain
Leg edema
Bowel/bladder symptoms
Physical Findings
• Exophytic, cauliflower like mass
• Cervical ulcer, friable or necrotic
• Firm “barrel-shaped” cervix
• Hydronephrosis
• Anemia
• Weight loss
Histology
Squamous
85-90%
Adenocarcinoma
10-15%
Lymphoma
Neuroendocrine/small cell
Melanoma
Route of Spread
Cervical cancer spreads by direct
invasion or by lymphatic spread
Vascular spread is rare
Staging
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Physical exam
Cervical biopsies
Chest x-ray
IVP (Ct scan)
Barium enema, cystoscopy, proctoscopy
Surgical staging
Staging
Stage I – confined to the cervix
IA1 – <3mm depth of invasion
IA2 – stromal invasion 3-5mm in depth
or <7 mm in width
IB1- tumor < 4 cm
IB2 - tumor > 4 cm in diameter
Stage II – extension beyond cervix
IIA – upper 2/3 of vagina
IIB – Parametrial involvement
Staging
Stage III
IIIA – lower 1/3 of vagina
IIIB – extension to pelvic sidewall or
hydronephrosis
Stage IV
IVA – bladder or rectal mucosa
IVB – distant metastases
5 year survival rates
Stage IA
Stage IB
Stage II
Stage III
Stage IV
90-100%
70-90%
50-60%
30-40%
5%
Therapy
Cervical conization
Simple hysterectomy
Radical hysterectomy
Radiation therapy with
chemosensitization
5 year Survival
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Stage I
Stage II
Stage III
Stage IV
70%
51%
33%
17%
Pros and Cons
Surgery
Bladder dysfunction
Vesico/uretero fistula
Bowel obstruction
Ovarian preservation
Vaginal preservation
Radiation
Sigmoiditis
Rectovaginal fistula
Bowel obstruction
Vesico/uretero fistula
Ovarian failure
Radiation Therapy
External Beam
Whole pelvis or para-aortic window
4000-6000 cGy
Over 4-5 weeks
Brachytherapy
Intracavitary or interstitial
2000-3000 cGy
Over 2 implants
Recurrent Cervical Cancer
10-20% of patients treated with
radical hysterectomy
Recurrence has an 85% mortality
83% are diagnosed within the first two
years of post-treatment surveillance
Recurrent Cervical Cancer
Radiation
Pelvic exenteration
Palliative chemotherapy
Vulvar Cancer
• 3870 new cases 2005
• 870 deaths
• Approximately 5% of Gynecologic
Cancers
American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005
Vulvar Cancer
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85% Squamous Cell Carcinoma
5% Melanoma
2% Sarcoma
8% Others
Vulvar Cancer
• Biphasic Distribution
• Average Age 70 years
• 20% in patients UNDER 40 and appears to
be increasing
Vulvar Cancer Etiology
• Chronic inflammatory conditions and
vulvar dystrophies are implicated in older
patients
• Syphilis and lymphogranuloma venereum
and granuloma inguinal
• HPV in younger patients
• Tobacco
Vulvar Cancer
• Paget’s Disease of Vulva
– 10% will be invasive
– 4-8% association with underlying
Adenocarcinoma of the vulva
Symptoms
• Most patients are treated for “other”
conditions
• 12 month or greater time from symptoms to
diagnosis
Symptoms
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Pruritus
Mass
Pain
Bleeding
Ulceration
Dysuria
Discharge
Groin Mass
Symptoms
• May look like:
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Raised
Erythematous
Ulcerated
Condylomatous
Nodular
Vulvar Cancer
• IF IT LOOKS ABNORMAL ON THE
VULVA
• BIOPSY!
• BIOPSY!
• BIOPSY!
Tumor Spread
• Very Specific nodal spread pattern
• Direct Spread
• Hematogenous
Staging
• Based on TNM Surgical Staging
– Tumor size
– Node Status
– Metastatic Disease
Staging
• Stage I T1 N0 M0
– Tumor ≤ 2cm
– IA
– IB
≤1 mm depth of Invasion
1 mm or more depth of invasion
Staging
• Stage II T2 N0 M0
– Tumor >2 cm
– Confined to Vulva or Perineum
Staging
• Stage III
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T3 N0 M0
T3 N1 M0
T1 N1 M0
T2 N1 M0
• Tumor any size involving lower urethra, vagina,
anus OR unilateral positive nodes
Staging
• Stage IVA
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T1 N2 M0
T2 N2 M0
T3 N2 M0
T4 N any M0
• Tumor invading upper urethra, bladder, rectum,
pelvic bone or bilateral nodes
Staging
• Stage IVB
– Any T Any N M1
• Any distal mets including pelvic nodes
Treatment
• Primarily Surgical
– Wide Local Excision
– Radical Excision
– Radical Vulvectomy with Inguinal Node
Dissection
• Unilateral
• Bilateral
• Possible Node Mapping, still investigational
Treatment
• Local advanced may be treated with
Radiation plus Chemosensitizer
• Positive Nodal Status
– 1 or 2 microscopic nodes < 5mm can be
observed
– 3 or more or >5mm post op radiation
Treatment
• Special Tumor
– Verrucous Carcinoma
• Indolent tumor with local disease, rare mets
UNLESS given radiation, becomes Highly
malignant and aggressive
• Excision or Vulvectomy ONLY
Vulva 5 year survival
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Stage I
Stage II
Stage III
Stage IV
90
77
51
18
Hacker and Berek, Practical Gynecologic Oncology
4th Edition, 2005
Recurrence
• Local Recurrence in Vulva
– Reexcision or radiation and good prognosis if
not in original site of tumor
– Poor prognosis if in original site
Recurrence
• Distal or Metastatic
– Very poor prognosis, active agents include
Cisplatin, mitomycin C, bleomycin,
methotrexate and cyclophosphamide
Melanoma
• 5% of Vulvar Cancers
• Not UV related
• Commonly periclitoral or labia minora
Melanoma
• Microstaged by one of 3 criteria
– Clark’s Level
– Chung’s Level
– Breslow
Melanoma Treatment
• Wide local or Wide Radical excision with
bilateral groin dissection
• Interferon Alpha 2-b
Vaginal Carcinoma
• 2140 new cases projected 2005
• 810 deaths projected 2005
• Represents 2-3% of Pelvic Cancers
American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005
Vaginal Cancer
• 84% of cancers in vaginal area are
secondary
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Cervical
Uterine
Colorectal
Ovary
Vagina
Fu YS, Pathology of the Uterine Cervix, Vagina and Vulva,
nd
Vaginal Carcinoma
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Squamous Cell
Clear Cell
Sarcoma
Melanoma
80-85%
10%
3-4%
2-3%
Clear Cell Carcinoma
• Associated with DES Exposure In Utero
– DES used as anti abortifcant from 1949-1971
– 500+ cases confirmed by DES Registry
– Usually occurred late teens
Vaginal Cancer Etiology
• Mimics Cervical Carcinoma
– HPV 16 and 18
Staging
• Stage I
• Stage II
Confined to Vaginal Wall
Subvaginal tissue but not
to pelvic sidewall
• Stage III Extended to pelvic
sidewall
• Stage IVA
Bowel or Bladder
• Stage IVB
Distant mets
Treatment
• Surgery with Radical Hysterectomy and
pelvic lymph dissection in selected stage I
tumors high in Vagina
• All others treated with radiation with
chemosensitization