The Management of Cervical , Vulvar and Vaginal Cancers

1. The Management of Cervical , Vulvar and Vaginal Cancers Kerry J. Rodabaugh, M.D. Division of Gynecologic Oncology University of Nebraska Medical Center Updated 7/2019

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 • 12-15.9/100,000: 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. 2012 Screening Guidelines for the Early Detection of Cervical Cancer • Age 21-29. Testing with cytology (Pap) alone every 3 years. • Co-testing should NOT be performed for women < age 30. • Reflex HPV testing for ASCUS only. • Saslow et al. ACS/ASCCP/ASCP. CA Cancer J Clin 2012; 62: 147-72 and AJCP 2012; 137: 516 – 542. • Moyer VA, et al. USPSTF. Ann Int Med 2012; 156: 880-91 • ACOG Practice Bulletin #131, November 2012 • NCCN Cervical Cancer Screening Guideline v. 2-2012. www.NCCN.org

8. 2012 Screening Guidelines for the Early Detection of Cervical Cancer • Age 30-65. Testing with cytology alone every 3 years or co-testing with cytology and testing for high-risk HPV types every 5 years. • Co-testing “preferred” and cytology “acceptable” by all but USPSTF • Recommendations NOT intended for women with HIV, immunocompromised, or in-utero DES exposure • Saslow et al. ACS/ASCCP/ASCP. CA Cancer J Clin 2012; 62: 147-72 and AJCP 2012; 137: 516 – 542. • Moyer VA, et al. USPSTF. Ann Int Med 2012; 156: 880-91 • ACOG Practice Bulletin #131, November 2012 • NCCN Cervical Cancer Screening Guideline v. 2-2012. www.NCCN.org

9. 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.

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

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

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

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

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

16. Staging Stage I – confined to the cervix IA – <5mm maximum depth of invasion IA1 – <3mm depth of invasion IA2 – stromal invasion ≥3mm and <5 mm depth of invasion IB – ≥5 mm maximum depth of invasion (greater than Stage IA) IB1 – tumor ≥5 mm depth of stromal invasion and <2 cm in dimension IB2 – tumor ≥2 cm and <4 cm in dimension IB3 – ≥4 cm in dimension

17. Staging Stage II – extension beyond cervix, IIA – upper 2/3 of vagina without parametrial involvement IIA1 – <4 cm in greatest dimension IIA2 – ≥4 cm in greatest dimension IIB – parametrial involvement not up to pelvic wall

18. Staging Stage III – Lower 1/3 of vagina, extends to the pelvic wall, causes hydronephrosis or nonfunctioning kidney, involves pelvic, para-aortic lymph nodes IIIA – lower 1/3 of vagina, no extension to pelvic wall IIIB – extension to pelvic wall or hydronephrosis or nonfunctioning kidney IIIC – involvement of pelvic or para-aortic lymph nodes, irrespective of tumor size and extent IIIC1 – pelvic lymph node metastasis only IIIC2 – para-aortic lymph node metastasis

19. Staging Stage IV – Extended beyond the true pelvis or involved bladder or rectum IVA – adjacent pelvic organs IVB – distant metastases

21. 5 year survival rates Stage IA 90-100% Stage IB 70-90% Stage II 50-60% Stage III 30-40% Stage IV 5%

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

26. 5 year Survival • Stage I 70% • Stage II 51% • Stage III 33% • Stage IV 17%

27. 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

28. 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

31. 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

32. Recurrent Cervical Cancer Radiation Pelvic exenteration Palliative chemotherapy

33. Vulvar Cancer • 3870 new cases 2005 • 870 deaths • Approximately 5% of Gynecologic Cancers American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005

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

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

36. 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

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

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

41. Symptoms • Pruritus • Mass • Pain • Bleeding • Ulceration • Dysuria • Discharge • Groin Mass

42. Symptoms • May look like: • Raised • Erythematous • Ulcerated • Condylomatous • Nodular

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

44. Tumor Spread • Very Specific nodal spread pattern • Direct Spread • Hematogenous

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

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

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

48. 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

49. 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

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