1. The Management of Cervical , Vulvar and Vaginal Cancers
Kerry J. Rodabaugh, M.D.
Division of Gynecologic Oncology
University of Nebraska Medical Center

2. 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

3. United States Incidence
15,000 women diagnosed annually 4,800 annual deaths

4. Mortality Rates
<2/100,000: Finland, France, Greece, Israel, Japan, Korea, Spain, Thailand
2.7/100,000: USA
/100,000: Chile, Costa Rica, Mexico

5. Lifetime risk of developing cervical cancer
5% - South America 0.7% - USA

6. 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

7. 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.
The American Cancer Society cervical cancer screening guidelines state that women should begin screening approximately three years after she 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 tests in a row may get screened every 2-3 years. Women 70 and older who have had three or more consecutive normal Pap tests in the last 10 years may choose to stop cervical cancer screening.
American Cancer Society. Cancer Facts & Figures Atlanta, GA; 2005

8. 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.

9. Clinical Presentation
CIN/CIS/ACIS – asymptomatic
Irregular vaginal bleeding
Vaginal discharge
Pelvic pain
Leg edema
Bowel/bladder symptoms

10. Physical Findings Exophytic, cauliflower like mass
Cervical ulcer, friable or necrotic
Firm “barrel-shaped” cervix
Hydronephrosis
Anemia
Weight loss

12. Histology Squamous 85-90% Adenocarcinoma 10-15% Lymphoma
Neuroendocrine/small cell
Melanoma

13. Route of Spread
Cervical cancer spreads by direct invasion or by lymphatic spread Vascular spread is rare

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

15. 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

16. 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

18. 5 year survival rates
Stage IA % Stage IB 70-90% Stage II 50-60% Stage III 30-40% Stage IV 5%

19. Therapy
Cervical conization Simple hysterectomy Radical hysterectomy Radiation therapy with chemosensitization

23. 5 year Survival
Stage I 70%
Stage II 51%
Stage III 33%
Stage IV 17%

24. Pros and Cons Surgery Radiation Bladder dysfunction
Vesico/uretero fistula
Bowel obstruction
Ovarian preservation
Vaginal preservation
Radiation
Sigmoiditis
Rectovaginal fistula
Bowel obstruction
Vesico/uretero fistula
Ovarian failure

25. Radiation Therapy External Beam Brachytherapy
Whole pelvis or para-aortic window
cGy
Over 4-5 weeks
Brachytherapy
Intracavitary or interstitial
cGy
Over 2 implants

28. 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

29. Recurrent Cervical Cancer
Radiation Pelvic exenteration Palliative chemotherapy

30. Vulvar Cancer 3870 new cases 2005 870 deaths
Approximately 5% of Gynecologic Cancers
American Cancer Society. Cancer Facts & Figures Atlanta, GA; 2005

31. Vulvar Cancer 85% Squamous Cell Carcinoma 5% Melanoma 2% Sarcoma
8% Others

32. Vulvar Cancer Biphasic Distribution Average Age 70 years
20% in patients UNDER 40 and appears to be increasing

33. 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

34. Vulvar Cancer Paget’s Disease of Vulva 10% will be invasive
4-8% association with underlying Adenocarcinoma of the vulva

37. Symptoms Most patients are treated for “other” conditions
12 month or greater time from symptoms to diagnosis

38. Symptoms Pruritus Mass Pain Bleeding Ulceration Dysuria Discharge
Groin Mass

39. Symptoms May look like: Raised Erythematous Ulcerated Condylomatous
Nodular

40. Vulvar Cancer
IF IT LOOKS ABNORMAL ON THE VULVA
BIOPSY!

41. Tumor Spread Very Specific nodal spread pattern Direct Spread
Hematogenous

42. Staging Based on TNM Surgical Staging Tumor size Node Status
Metastatic Disease

43. Staging Stage I T1 N0 M0 Tumor ≤ 2cm IA ≤1 mm depth of Invasion
IB 1 mm or more depth of invasion

44. Staging
Stage II T2 N0 M0
Tumor >2 cm
Confined to Vulva or Perineum

45. Staging Stage III T3 N0 M0 T3 N1 M0 T1 N1 M0 T2 N1 M0
Tumor any size involving lower urethra, vagina, anus OR unilateral positive nodes

46. Staging Stage IVA T1 N2 M0 T2 N2 M0 T3 N2 M0 T4 N any M0
Tumor invading upper urethra, bladder, rectum, pelvic bone or bilateral nodes

47. Staging Stage IVB Any T Any N M1
Any distal mets including pelvic nodes

48. Treatment Primarily Surgical Wide Local Excision Radical Excision
Radical Vulvectomy with Inguinal Node Dissection
Unilateral
Bilateral
Possible Node Mapping, still investigational

49. 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

50. Treatment Special Tumor Verrucous Carcinoma
Indolent tumor with local disease, rare mets UNLESS given radiation, becomes Highly malignant and aggressive
Excision or Vulvectomy ONLY

51. Vulva 5 year survival Stage I 90 Stage II 77 Stage III 51 Stage IV 18
Hacker and Berek, Practical Gynecologic Oncology 4th Edition, 2005

52. Recurrence Local Recurrence in Vulva
Reexcision or radiation and good prognosis if not in original site of tumor
Poor prognosis if in original site

53. Recurrence Distal or Metastatic
Very poor prognosis, active agents include Cisplatin, mitomycin C, bleomycin, methotrexate and cyclophosphamide

54. Melanoma 5% of Vulvar Cancers Not UV related
Commonly periclitoral or labia minora

55. Melanoma Microstaged by one of 3 criteria Clark’s Level Chung’s Level
Breslow

56. Melanoma Treatment
Wide local or Wide Radical excision with bilateral groin dissection
Interferon Alpha 2-b

57. Vaginal Carcinoma 2140 new cases projected 2005
810 deaths projected 2005
Represents 2-3% of Pelvic Cancers
American Cancer Society. Cancer Facts & Figures Atlanta, GA; 2005

58. Vaginal Cancer 84% of cancers in vaginal area are secondary Cervical
Uterine
Colorectal
Ovary
Vagina
Fu YS, Pathology of the Uterine Cervix, Vagina and Vulva, 2nd ed

59. Vaginal Carcinoma Squamous Cell 80-85% Clear Cell 10% Sarcoma 3-4%
Melanoma 2-3%

60. Clear Cell Carcinoma Associated with DES Exposure In Utero
DES used as anti abortifcant from
500+ cases confirmed by DES Registry
Usually occurred late teens

61. Vaginal Cancer Etiology
Mimics Cervical Carcinoma
HPV 16 and 18

62. Staging Stage I Confined to Vaginal Wall
Stage II Subvaginal tissue but not to pelvic sidewall
Stage III Extended to pelvic sidewall
Stage IVA Bowel or Bladder
Stage IVB Distant mets

63. Treatment
Surgery with Radical Hysterectomy and pelvic lymph dissection in selected stage I tumors high in Vagina
All others treated with radiation with chemosensitization