Vulvar and vaginal cancer

Vulvar cancer is a malignancy of the outer female genitalia that predominantly occurs in postmenopausal women. Major risk factors are HPV infection, smoking, vulvar dystrophy, and vulvar or cervical intraepithelial neoplasia. Clinical manifestations of vulvar cancer include new lumps or lesions, itching, a burning sensation and, less frequently, vulvar bleeding. Suspicious lesions must be biopsied for histological analysis and to rule out other similar conditions, such as vulvar dermatoses or vulvar intraepithelial neoplasia, which both increase the risk of vulvar cancer. Vulvar cancer is staged based on the depth of the lesion and the involvement of neighboring structures. Surgical resection (radical vulvectomy) is the first-line treatment, but advanced stages may require radiotherapy and/or palliative chemotherapy. Vulvar cancer is usually associated with a poor prognosis.

Vaginal cancer is closely related to vulvar cancer in terms of etiology and histology, but it occurs inside the vagina (typically the posterior third of the vaginal wall), rather than the vulva.

• Incidence: rare ^[1]
• Age ^[2]
  • HPV-related vulvar cancer: 35–65 years
  • Non-HPV related types: 55–85 years

Epidemiological data refers to the US, unless otherwise specified.

Risk factors ^[3]

• Infection with HPV 16, 18, 31, and 33 (16 and 33 account for 55% of HPV-related cases of vulvar cancer)
• Vulvar dystrophy and vulvar or cervical intraepithelial neoplasia (VIN/CIN)
• Smoking
• Precancerous lesions (e.g., lichen sclerosus)
• Immunosuppression

• Squamous cell carcinoma (> 80% of cases)
• Basal cell carcinoma
• Melanoma
• Paget disease of the vulva (see below)

• Pathology
  • Adenocarcinoma; carcinoma in situ
  • Low risk (< 15%) of underlying invasive Paget disease/invasive adenocarcinoma (unlike Paget disease of the breast which is always associated with underlying carcinoma)
• Clinical features
  • Eczematoid lesions
    • Raised, well-demarcated borders
    • Erythematous patches with white scaling
    • Crusting and ulcerations
  • Local pruritus

• May initially be asymptomatic ^[2]
• Local pruritus, possibly with burning sensation and pain
• Reddish, blackish, and/or whitish patches of discoloration
• Lumps or growths of various shapes, often wart-like lesions or ulcers
• Vulvar bleeding or discharge (less common)
• Dysuria, dyspareunia
• Lymphadenopathy in the groin area

• Pelvic exam and colposcopy
• Biopsy

All suspicious lesions must be biopsied for histological analysis.

Vulvar dermatoses

Vulvar dermatoses are not inherently precancerous, but they do increase the risk of squamous cell carcinoma.

• Subtypes
  • Lichen sclerosus: epidermal atrophy and loss of vulvar architecture
  • Lichen simplex chronicus: squamous cell hyperplasia
  • Other dermatoses, e.g., genital lichen planus (hypertrophied skin with purple lesions)
• Etiology: unclear
• Epidemiology: postmenopausal women and, less commonly, prepubescent girls
• Clinical features
  • Parchment-like, thin, shiny vulvar skin
  • Narrow, atrophic vaginal introitus resulting in dyspareunia
  • Burning pain, pruritus, bleeding vulvar ulcers
  • Lichen simplex chronicus is characterized by chronic pruritus, which provokes persistent scratching of the vulva and so causes lichenification of the skin.
• Diagnosis: Colposcopy and biopsy of suspicious lesions are required to rule out malignancy.
• Histology
  • Epidermal atrophy, localized hyperkeratosis, degeneration of the basement membrane
  • Loss of collagenous and elastic connective tissue
  • Presence of an inflammatory infiltrate
• Therapy
  • Without atypical cellular morphology: local therapy with glucocorticoid-containing creams
  • In the event of malignancy: surgical resection of the lesion

Vulvar intraepithelial neoplasia (VIN)

• Definition: precancerous lesion caused by dysplasia of squamous cells
• Classification ^[4]
  • VIN, usual type (most common)
    • Associated with HPV
    • Commonly multifocal
  • VIN, differentiated type
    • Associated with lichen sclerosus and other dermatoses
    • Commonly unifocal
  • VIN, unclassified type
• Diagnosis: tissue biopsy
• Treatment: : depending on severity, excision or ablation may become necessary
• Prognosis: may progress to vulvar carcinoma despite treatment (in < 10% of cases)

The differential diagnoses listed here are not exhaustive.

• First-line treatment; : local excision and surgical resection (radical vulvectomy) ^[5]
• Radiotherapy and/or palliative chemotherapy: when disease metastasizes to peripheral lymph nodes or other organs

• The average 5-year survival rates range from 30–50%.
• Survival rates vary greatly depending on the stage of the disease.

Overview

• Localization: The upper third of the posterior vaginal wall is the most common site of vaginal carcinoma.
• Etiology: same as vulvar neoplasia (e.g., HPV 16 and 18)

Subtypes

• Squamous cell carcinoma
  • Most common type
  • Usually occurs secondary to cervical squamous cell carcinoma, primary carcinoma is rare
• Clear cell adenocarcinoma
  • Usually occurs secondary to vaginal adenosis (the presence of glandular columnar epithelium within the upper two-thirds of the vaginal wall)
  • Seen in daughters of women who received diethylstilbestrol during pregnancy
• Sarcoma botryoides ^[6]
  • Rare, highly malignant embryonal rhabdomyosarcoma that arises most commonly, but not exclusively in the genitourinary system
  • Epidemiology: peak incidence in childhood (< 4 years) ^[7]
  • Pathology
    • Gross: clear, polypoid masses that resemble a bunch of grapes protruding through the vagina
    • Microscopy: pleomorphic spindle-shaped cells
    • Immunohistochemical staining: desmin positive

Symptoms

• Vaginal bleeding
• Leukoplakia, vaginal ulceration with contact bleeding
• Malodorous discharge
• Possibly urinary frequency

Diagnosis

• Pelvic exam
• Colposcopy: if abnormal cytology results without a clearly visible lesion during pelvic exam
• Biopsy of mass to determine histopathology

Therapy

• Radiotherapy
  • Indicated in squamous cell carcinomas
  • Preserves external genitalia
• Surgical therapy

Senile vaginitis should also be considered in patients presenting with vaginal pruritus, burning, and pain.