The Management of Cervical Vulvar and Vaginal

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 • • 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 • • • 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 • • • Physical exam Cervical biopsies Chest x-ray IVP (Ct scan) Barium enema, cystoscopy, proctoscopy Surgical staging

Staging Stage I – confined to the cervix IA 1 – <3 mm depth of invasion IA 2 – stromal invasion 3 -5 mm in depth or <7 mm in width IB 1 - tumor < 4 cm IB 2 - tumor > 4 cm in diameter Stage II – extension beyond cervix IIA – upper 2/3 of vagina IIB – Parametrial involvement

Staging Stage 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 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 • • 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 c. Gy Over 4 -5 weeks Brachytherapy Intracavitary or interstitial 2000 -3000 c. Gy 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 • • 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 • • Pruritus Mass Pain Bleeding Ulceration Dysuria Discharge Groin Mass

Symptoms • May look like: – Raised – Erythematous – Ulcerated – Condylomatous – Nodular

Vulvar Cancer • IF IT LOOKS ABNORMAL ON THE VULVA • 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 T 1 N 0 M 0 – Tumor ≤ 2 cm – IA – IB ≤ 1 mm depth of Invasion 1 mm or more depth of invasion

Staging • Stage II T 2 N 0 M 0 – Tumor >2 cm – Confined to Vulva or Perineum

Staging • Stage III – T 3 N 0 M 0 – T 3 N 1 M 0 – T 1 N 1 M 0 – T 2 N 1 M 0 • Tumor any size involving lower urethra, vagina, anus OR unilateral positive nodes

Staging • Stage IVA – T 1 N 2 M 0 – T 2 N 2 M 0 – T 3 N 2 M 0 – T 4 N any M 0 • Tumor invading upper urethra, bladder, rectum, pelvic bone or bilateral nodes

Staging • Stage IVB – Any T Any N M 1 • Any distal mets including pelvic nodes

Treatment • Primarily Surgical – Wide Local 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 < 5 mm can be observed – 3 or more or >5 mm 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 • • Stage III Stage IV 90 77 51 18 Hacker and Berek, Practical Gynecologic Oncology 4 th 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 – Cervical – Uterine – Colorectal – Ovary – Vagina Fu YS, Pathology of the Uterine Cervix, Vagina and nd

Vaginal Carcinoma • • 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 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