Vulva Neoplasia

85% of cancers of the vulva are squamous and the remaining are of various histological types, including melanomas. The labia majora is the most common site of involvement and accounts for about 50% of cases. The labia minora accounts for about 20% of cases.¹ The clitoris and Bartholin's glands are less frequently involved. Usually spreads slowly, locally and metastasises to groin nodes and from then to pelvic nodes.

• Vulvar cancer is primarily a disease of elderly women but has been observed in pre-menopausal women as well.
• In many cases, the development of vulvar cancer is preceded by condyloma or squamous dysplasias.
• Almost two-thirds of vulval cancers occur in women who have lichen sclerosus, but only a small percentage (1-2%) of women who have lichen sclerosus will go on to develop vulval cancer.
• Human papillomavirus (HPV) is a causative factor in genital tract carcinomas.
• Smoking increases the risk carcinoma in situ and cancer of the vulva.¹

• Vulval cancer may present with a vulval lump, vulval bleeding due to ulceration, pruritus or pain.
• The pattern of spread is influenced by the histology. Well-differentiated lesions tend to spread along the surface with minimal invasion, while anaplastic lesions are more likely to be deeply invasive.
• Spread beyond the vulva is either to adjacent organs such as the vagina, urethra, and anus, or via the lymphatics to the inguinal and femoral lymph nodes, followed by the deep pelvic nodes.
• Approximately 5% of cases spread to distant sites.

• The diagnosis of vulvar cancer is made by biopsy.
• Cystoscopy, proctoscopy, chest x-ray and intravenous urography are used for staging purposes.

• Lichen planus
• Ulcers: e.g. herpes, Crohn's, Behcets disease, syphilis
• Dermatitis
• Fungal infection
• Other causes of swellings of the vulva include boils, sebaceous cysts, Bartholin's cyst or abscess and urethral caruncle

Stages are defined by the Federation Internationale de Gynecologie et d'Obstetrique (FIGO) and the American Joint Committee on Cancer's (AJCC) TNM classifications.²

TNM Category/FIGO Stage

Primary tumour (T)

• TX: Primary tumour cannot be assessed
• T0: No evidence of primary tumour
• Tis/0: Carcinoma in situ (preinvasive carcinoma)
• T1/I: Tumour confined to the vulva or vulva and perineum, 2 cm or less in greatest dimension
• T1a/IA: Tumour confined to the vulva or vulva and perineum, 2 cm or less in greatest dimension, and with stromal invasion no greater than 1 mm.
• T1b/IB: Tumour confined to the vulva or vulva and perineum, 2 cm or less in greatest dimension, and with stromal invasion greater than 1 mm.
• T2/II: Tumour confined to the vulva or vulva and perineum, more than 2 cm in greatest dimension
• T3/III: Tumour of any size with contiguous spread to the lower urethra and/or vagina or anus
• T4/IVA: Tumour invades any of the following: upper urethra, bladder mucosa, rectal mucosa, or is fixed to the pubic bone

Regional lymph nodes (N)

• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1/III: Unilateral regional lymph node metastasis
• N2/IVA: Bilateral regional lymph node metastasis

Distant metastasis (M)

• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1/IVB: Distant metastasis (including pelvic lymph node metastasis)

AJCC stage groupings

• Stage 0: Tis, N0, M0
• Stage I: T1, N0, M0
• Stage IA: T1a, N0, M0
• Stage IB: T1b, N0, M0
• Stage II: T2, N0, M0
• Stage III: T1, N1, M0; T2, N1, M0; T3, N0, M0; T3, N1, M0
• Stage IVA: T1, N2, M0; T2, N2, M0; T3, N2, M0; T4, any N, M0
• Stage IVB: Any T, any N, M1

• Pre-invasive carcinoma
  • Simple vulvectomy gives a 5-year survival rate of essentially 100% but is seldom indicated. Other, more limited, surgical procedures produce equivalent results and are less deforming.
  • Vulvar intra-epithelial neoplasia occupying non-hairy areas can be considered an epithelial disease. With involvement of hairy sites, the pilo-sebaceous gland in usually involved and so requires a greater depth of destruction or excision.
  • Irrespective of the procedure, a significant number of patients develop a recurrence with the most common sites being the perianal skin, presacral area and clitoris.
  • Laser excision treatment is an alternative to surgery or an adjunct for those areas difficult to remove by surgery. Laser treatment is followed by a higher recurrence rate.
  • Topical 5% fluorouracil cream is not a reliable first choice for treatment but is useful for women when complete surgical resection is not possible. Topical steroids may be used to relieve associated irritation but is not a curative treatment.
• Standard treatment in vulvar cancer is surgery, including bilateral inguinal lymphadenectomy. For most patients with stage III or IV disease, surgery is supplemented by external-beam radiation therapy.
• Newer strategies integrate possible therapeutic advantages of surgery, radiation therapy and chemotherapy.
• Preoperative treatment with chemotherapy and radiotherapy reduces tumour size and improves the chances of surgical excision in women with initially inoperable primary tumours or fixed lymph nodes, but side effects (skin toxicity, wound breakdown, infection, lymphoedema and lymphoceles) are considerable.³
• In patients with large tumours, the complications of radiotherapy and chemotherapy followed by surgery might outweigh complications of surgery alone. Radiotherapy and chemotherapy treatment is not justified in patients with tumours that can be adequately treated with removal of the tumour by vulvectomy and bilateral groin node dissection alone.³
• Chemotherapy:
  • Pre-operative chemoradiotherapy (using 5-fluorouracil and mitomycin C) can reduce the size of large carcinomas and reduce the extent of surgery necessary.
  • Chemotherapy alone with bleomycin, methotrexate, and CCNU has been used successfully.⁴
  • However the results of chemotherapy for advanced and recurrent disease have overall been disappointing.²
• Because of the psychosexual consequences and significant morbidity associated with standard radical vulvectomy, there is now a preference towards conserving the vulva when possible.
• Invasive and pre-invasive neoplasms of the vulva may be HPV-induced and so close follow-up is required for early detection of recurrent or second tumours.

• Vulvar cancer is curable when diagnosed in an early stage.
• Operable disease without nodal involvement: the overall survival rate is 90%.
• Nodal involvement: the overall 5-year survival rate is approximately 50% to 60%.