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Older patients with associated medical problems are at high risk from radical surgery. The surgery, however, is usually well tolerated.
Patients who are not surgical candidates can be treated with combination chemotherapy and/or radiation.
In the very elderly, palliative vulvectomy provides relief of symptoms for ulcerating symptomatic advanced disease.
EPIDEMIOLOGY
Incidence
- In 2015, 5,150 women were diagnosed with vulvar cancer and 1,080 women died from vulvar cancer in the United States (2).
- Ethnic distribution: more common in Caucasian women than in any other race
- Surveillance, epidemiology, and end result (SEER) data showed that the incidence of in situ vulvar carcinoma increased by >400% between 1973 and 2000.
- Mean age at diagnosis 65 years; in situ disease: mean age 40 years; invasive malignancy: mean age 60 years (3)
ETIOLOGY AND PATHOPHYSIOLOGY
- Patients with cervical cancer are more likely to develop vulvar cancer later in life, secondary to "field effect " phenomenon with a carcinogen involving the lower genital tract (3).
- HPV has been associated with squamous cell abnormalities of the cervix, vagina, and vulva; 55% of vulvar cancers are attributable to oncogenic HPV, predominantly HPV 16 and 33; 92% of VIN 2/3, vaginal intraepithelial neoplasia (VAIN) 2/3, and anal intraepithelial neoplasia (AIN) are attributable to HPV.
- Squamous cell carcinoma
- The warty basaloid type, also known as bowenoid type, is related to HPV infection and occurs in younger women. Although traditionally graded in a three-level system, the International Society for the Study of Vulvovaginal Disease voted not to use a grading system for VIN in 2004. This system eliminated VIN 1 and combined VIN 2 and VIN 3. This is based on the fact that VIN 1 is not reproducible. VIN 2 and VIN 3 were combined because VIN 2 is rare and carries the same risk of progression to malignancy as VIN 3 (1).
- The more common variant is simplex or differentiated and does not appear to be related to HPV, occurs in older age groups, and associated with lichen sclerosus and chronic venereal diseases; it is thought to carry a higher risk of progression to malignancy.
- Melanoma, second most common histology, often identified in postmenopausal women; often pigmented but can be amelanotic, arising de novo, often found on clitoris or labia minora (1).
- Cases not associated with HPV infection are typically associated with vulvar dystrophies, such as lichen sclerosus or squamous cell hyperplasia.
- Smoking is associated with squamous cell disease of the vulva, possibly from direct irritation of the vulva by the transfer of tars and nicotine on the patient 's hands or from systemic absorption of carcinogen.
Genetics
No known genetic pattern
RISK FACTORS
- VIN or cervical intraepithelial neoplasia (CIN)
- Smoking
- Lichen sclerosus (vulvar dystrophy)
- HPV infection, condylomata or sexually transmitted diseases (STD) in the past
- Low economic status
- Autoimmune processes
- Immunodeficiency syndromes or immunosuppression
- Northern European ancestry
GENERAL PREVENTION
- HPV vaccination has the potential to decrease vulvar cancer by 60% (3, 4, 5).
- Abstinence from smoking/smoking cessation counseling (1)
COMMONLY ASSOCIATED CONDITIONS
- Patients with invasive vulvar cancer are often elderly and have associated medical conditions.
- High rate of other gynecologic malignancies
DIAGNOSIS
HISTORY
Complaints of pruritus or raised lesion in the vaginal area
PHYSICAL EXAM
- In situ disease: a small raised area associated with pruritus, single vulvar plaque, ulcer, or mass on labia majora, perineum, clitoris
- Vulvar bleeding, dysuria, enlarged lymph nodes less common symptomatology
- Invasive malignancy: an ulcerated, nonhealing area; as lesions become large, bleeding occurs with associated pain and foul-smelling discharge; enlarged inguinal lymph nodes indicative of advanced disease.
DIFFERENTIAL DIAGNOSIS
- Infectious processes can present as ulcerative lesions and include syphilis, lymphogranuloma venereum, and granuloma inguinale.
- Disorder of Bartholin gland, seborrheic keratosis, hidradenomas, lichen sclerosus, epidermal inclusion cysts
- Crohn disease can present as an ulcerative area on the vulva.
- Rarely, lesions can metastasize to the vulva.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Hypercalcemia can occur when metastatic disease is present.
- Squamous cell antigen can be elevated with invasive disease.
Follow-Up Tests & Special Considerations
- Upon examination, any suspicious lesions should be biopsied.
- Diagnosis based on histologic findings following vulvar biopsy (6)
- The vulva can be washed with 3% acetic acid to highlight areas and visualized with a colposcope, allows for visualization of acetowhite lesions and vascular lesions (6).
- For patients with new onset of pruritus, the area of pruritus should be biopsied.
- Liberal biopsies must be used to diagnose in situ disease prior to invasion and to diagnose early invasive disease.
- The patient should not be treated for presumed benign conditions of the vulva without full exam and biopsy, including Pap smear and colposcopy of cervix, vagina, and vulva.
- When symptoms persist, reexamine and rebiopsy.
- Treatment of benign condyloma of the vulva has not been shown to decrease the eventual incidence of in situ or invasive disease of the vulva.
- CT scan to evaluate pelvic and periaortic lymph node status if tumor >2 cm or if suspicion of metastatic disease (6)[A].
Diagnostic Procedures/Other
Office vulvar biopsy is done to establish the diagnosis.
Test Interpretation
A surgical staging system is used for vulvar cancer (International Federation of Obstetrics and Gynecology Classification).
- Stage I: tumor confined to the vulva
- Stage IA: lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1 mm, no node metastasis
- Stage IB: lesions >2 cm in size or with stromal invasion >1 mm, confined to the vulva or perineum, with negative nodes
- Stage II: tumor of any size with extension to adjacent perineal structures (lower 1/3 urethra, lower 1/3 vagina, anus) with negative nodes
- Stage III: tumor of any size with or without extension to adjacent perineal structures (lower 1/3 urethra, lower 1/3 vagina, anus) with positive inguinofemoral lymph nodes
- Stage IIIA
- With 1 lymph node metastasis ( ≥5 mm), or
- 1 to 2 lymph node metastases (<5 mm)
- Stage IIIB
- With ≥2 lymph node metastases ( ≥5 mm), or
- ≥3 lymph node metastases (<5 mm)
- Stage IIIC: with positive nodes with extracapsular spread
- Stage IV: tumor invades other regional (upper 2/3 urethra, upper 2/3 vagina) or distant structures
- Stage IVA: tumor invades any of the following:
- Upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone
- Fixed or ulcerated inguinofemoral lymph nodes
- Stage IVB: any distant metastasis, including pelvic lymph nodes (7)[B]
TREATMENT
GENERAL MEASURES
- Wide excision can be performed for carcinoma in situ, and any suspicious lesion should be excised for definitive diagnosis.
- Cystoscopy and sigmoidoscopy should be performed if there is a question of invasion into the urethra, bladder, or rectum.
MEDICATION
- As an adjuvant therapy, fluorouracil (Efudex) cream for in situ disease can produce occasional results but is not well tolerated because of irritation of the vulva (8)[A].
- Chemoradiotherapy with cisplatin and 5-fluorouracil (5-FU) has been successful in advanced or recurrent disease, although local morbidity is increased (8)[A].
- Contraindications: elderly patients: If chemotherapeutic agents are used, pay close attention to the patient 's performance status and ability to tolerate aggressive chemotherapy.
ISSUES FOR REFERRAL
Patients may need care from a gynecologic oncologist and/or a radiation oncologist.
ADDITIONAL THERAPIES
- Preoperative radiation therapy can be used in those with advanced vulvar cancer (6)[B].
- Adjuvant radiation should be considered with tumor size >4 cm, evidence of lymphovascular invasion, positive surgical margins, or lymph node involvement.
- Preoperative chemoradiation allows for a less radical surgical procedure in patients who are not surgical candidates (8)[A].
- Postoperative radiation decreases recurrence frequency and may improve survival (8)[A].
- Radiation is contraindicated with verrucous carcinoma because it induces anaplastic transformation and increases metastases.
SURGERY/OTHER PROCEDURES
- In situ disease can be treated with wide excision or laser vaporization of the affected area. Laser vaporization is preferable in the younger patient, whereas wide excision is preferable in the elderly patient, in whom the risk of invasive disease is also higher (6)[A].
- If tumor extension within <1 cm from structures that will not be removed, preoperative radiation to prevent inadequate surgical margins prior to excision
- Inguinofemoral lymphadenectomy removal of superficial inguinal and deep femoral lymph nodes
- 1 cm tumor-free margin is required because smaller margin would increase risk of recurrence (8)[A].
- Stage IA: radical local excision without lymph node dissection
- Stage IB: radical local excision with either sentinel lymph node biopsy (SLNB) or ipsilateral inguinofemoral lymph node dissection because the risk of metastases is >8%
- Stage II: modified radical vulvectomy and/or chemoradiation and groin node dissection
- Stages III and IV: neoadjuvant chemoradiation and less radical surgery
- Pelvic exenteration after radiation provides effective therapy for advanced or recurrent malignancies involving the bladder or rectum.
- More limited surgery
- Has been undertaken for early invasive lesions, especially in young patients, to preserve the clitoris and sexual function
- Sentinel lymph node biopsy (SLNB) also has been advocated for early invasive lesion (stage IB or higher). It has shown to accurately diagnose groin metastases in women with early vulval cancer and unknown groin node status. This will limit the surgical morbidity associated with inguinofemoral lymphadenectomy (IFL) in those with early stage disease (9)[A].
- Radical vulvectomy with bilateral groin node dissection through separate incisions provides better cosmetic results than en bloc technique.
- Unilateral lymphadenectomy should be considered when lesion <2 cm, lateral lesion >2 cm from vulvar midline, or no palpable groin nodes (7)[B].
INPATIENT CONSIDERATIONS
Typically inpatient for treatment
Admission Criteria/Initial Stabilization
In advanced malignancy involving the urethra and rectum, concomitant cisplatin/5-FU chemotherapy with radiation produces a significant decrease in size of the primary tumor, usually obviating the need for pelvic exenteration.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Early stage, treated with surgery alone: clinical exam of the groin nodes and vulvar area every 6 months for 2 years; then annually
- Following chemoradiation, assessment for further treatment within 6 to 12 weeks of therapy completion
- Advance stage, clinical exam of the groin nodes and vulvar area every 3 months for 2 years; then every 6 months for 3 years, and then annually (10)[B]
- Cervical and/or vaginal cytology annually
- Majority of relapses occur within 1st year.
DIET
As tolerated and according to comorbid conditions
PATIENT EDUCATION
- American College of Obstetricians and Gynecologists (ACOG), 409 12th St. SW, Washington, DC 20024-2188; (800) 762-ACOG; http://www.acog.org/
- American Cancer Society: http://www.cancer.org/
PROGNOSIS
The 5-year survival is based on stage:
- Stage I: 78.5%
- Stage II: 58.8%
- Stage III: 43.2%
- Stage IV: 13.0%
- Inguinal and/or femoral node involvement is the most important determinant of survival (11)[A].
COMPLICATIONS
- The major complications from radical vulvectomy and groin node dissection are wound breakdown, lymphedema, urinary stress incontinence, and psychosexual consequences.
- Two common complications with radical vulvectomy and bilateral groin node dissection
- In the immediate postoperative period, ~50% of patients experience breakdown of the wound. This requires aggressive wound care by visiting nurses as often as twice a day. The wounds usually granulate and heal over a period of 6 to 10 weeks.
- ~15 " 20% of patients experience some form of mild to moderate lymphedema after the groin node dissection. These patients should be instructed in the use of leg elevation and support hose. <1% of patients experience severe, debilitating lymphedema.
REFERENCES
11 Crosbie EJ, Slade RJ, Ahmed AS. The management of vulval cancer. Cancer Treat Rev. 2009;35(7):533 " 539.22 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5 " 29.33 U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999 " 2010 Incidence and Mortality Web-based Report. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2013.44 Hampl M, Sarajuuri H, Wentzensen N, et al. Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol. 2006;108(6):1361 " 1368.55 Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR " 2):1 " 24.66 de Hullu JA, van der Zee AG. Surgery and radiotherapy in vulvar cancer. Crit Rev Oncol Hematol. 2006;60(1):38 " 58.77 Radziszewski J, Kowalewska M, Jedrzejczak T, et al. The accuracy of the sentinel lymph node concept in early stage squamous cell vulvar carcinoma. Gynecol Oncol. 2010;116(3):473 " 477.88 Shylasree TS, Bryant A, Howells RE. Chemoradiation for advanced primary vulval cancer. Cochrane Database Syst Rev. 2011;13(4):CD003752.99 Lawrie TA, Patel A, Martin-Hirsch PP, et al. Sentinel node assessment for diagnosis of groin lymph node involvement in vulval cancer. Cochrane Database Syst Rev. 2014;(6):CD010409.1010 Stuckey A, Schutzer M, Rizack T, et al. Locally advanced vulvar cancer in elderly women: is chemoradiation beneficial? Am J Clin Oncol. 2013;36(3):279 " 282.1111 Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204(6):466 " 478.
CODES
ICD10
- C51.9 Malignant neoplasm of vulva, unspecified
- D07.1 Carcinoma in situ of vulva
- C51.0 Malignant neoplasm of labium majus
- C51.1 Malignant neoplasm of labium minus
- C51.8 Malignant neoplasm of overlapping sites of vulva
- C51.2 Malignant neoplasm of clitoris
ICD9
- 184.4 Malignant neoplasm of vulva, unspecified site
- 233.39 Carcinoma in situ, other female genital organ
- 184.1 Malignant neoplasm of labia majora
- 184.2 Malignant neoplasm of labia minora
- 184.3 Malignant neoplasm of clitoris
SNOMED
- 94143002 Primary malignant neoplasm of vulva
- 92802003 Carcinoma in situ of vulva (disorder)
- 93850006 Primary malignant neoplasm of labia majora
- 93851005 Primary malignant neoplasm of labia minora
- 254896002 Malignant melanoma of vulva (disorder)
- 371980003 Primary malignant neoplasm of clitoris
- 313351009 Bowen 's disease of vulva
- 254895003 Squamous cell carcinoma of vulva (disorder)
CLINICAL PEARLS
- 60% of vulvar cancers are attributable to oncogenic HPV, and 92% of all VIN 2/3, VAIN 2/3, and AIN are attributable to HPV. Therefore, HPV vaccination has the potential to decrease vulvar cancer by 1/3.
- Biopsy all suspicious or nonhealing vulvar lesions.