Cancer of the Vulva

Cancer of the vulva is a malignant neoplasm arising from the external female genitalia. It is predominantly a disease of older women and most commonly presents as squamous cell carcinoma. In many cases, vulvar cancer develops from premalignant lesions known as vulvar intraepithelial neoplasia (VIN). Early diagnosis and treatment are important because disease confined to the vulva is associated with better treatment outcomes, whereas advanced disease may require multimodal therapy and is associated with increased morbidity.

Epidemiology

Vulvar cancer is relatively uncommon compared with other gynecological malignancies. It primarily affects older women, although HPV-associated disease may occur in younger women. Squamous cell carcinoma is the most common histological subtype. The incidence is increased among women with persistent HPV infection and immunosuppression, particularly those living with HIV.

Risk factors

Risk factors for vulvar cancer include:

• Human papillomavirus (HPV) infection.

• Vulvar intraepithelial neoplasia (VIN).

• Human immunodeficiency virus (HIV) infection.

• Cigarette smoking.

• Persistent vulvar dystrophic lesions.

• Increasing age.

Pathophysiology

Most vulvar cancers arise from premalignant epithelial changes known as vulvar intraepithelial neoplasia. Persistent HPV infection may induce dysplastic changes within the vulvar epithelium, leading to progressive cellular atypia and malignant transformation. Over time, invasive carcinoma may develop and spread locally to adjacent structures, regional lymph nodes, and distant organs.

Clinical presentation

Patients commonly present with chronic vulvar symptoms that may initially be mistaken for benign dermatological conditions. Persistent itching, vulvar masses, and non-healing ulcers should raise suspicion for malignancy, particularly in older women.

Symptoms

• Persistent vulvar itching.

• Vulvar lump or mass.

• Non-healing vulvar ulcer.

• Vulvar discomfort.

• Pain in advanced disease.

• Bleeding from vulvar lesions.

• Symptoms related to locally advanced or metastatic disease.

Clinical signs

• Vulvar mass or lump.

• Leukoplakia involving the vulva.

• Dystrophic vulvar changes.

• Ulcerative vulvar lesions.

• Non-healing vulvar ulcers.

• Enlarged inguinal lymph nodes.

• Locally invasive lesions in advanced disease.

Differential diagnosis

Conditions that may mimic vulvar cancer include:

• Vulvar intraepithelial neoplasia (VIN).

• Lichen sclerosus.

• Chronic vulvitis.

• Vulvar candidiasis.

• Genital warts.

• Bartholin gland cyst or abscess.

• Vulvar tuberculosis.

• Syphilitic ulcer.

• Traumatic vulvar ulcers.

• Other benign vulvar dermatoses.

Diagnostic criteria

Vulvar cancer should be suspected in women presenting with:

• A vulvar lump or mass.

• Persistent vulvar itching.

• Leukoplakia or dystrophic vulvar lesions.

• Non-healing vulvar ulcers.

• Persistent vulvar lesions that fail to respond to treatment.

Definitive diagnosis requires histological confirmation from biopsy of the vulvar lesion.

Staging

Disease staging should be performed using:

• FIGO staging system.

• TNM staging system.

Investigations

Laboratory investigations

• Full blood count (FBC).

• Liver function tests (LFTs).

• Urea.

• Creatinine.

• HIV test.

Imaging investigations

• Chest X-ray (CXR).

• Ultrasonography of the abdomen and pelvis.

• Computed tomography (CT) scan of the abdomen and pelvis.

• Positron emission tomography/computed tomography (PET/CT).

Specialized investigations

• Colposcopy to assess for associated lesions of the cervix and vagina.

Histopathological investigations

• Biopsy of the vulvar lesion for definitive diagnosis.

Management

Management should be individualized according to:

• Histological type.

• Disease stage.

• Patient age.

• Performance status.

• Presence of local or distant spread.

Primary treatment is surgical whenever feasible.

Non-pharmacological treatment

Surgical treatment

The primary treatment is:

• Wide local excision (radical vulvectomy).

• Groin lymph node dissection.

Radiotherapy

Radiotherapy may be indicated in the following situations:

Primary treatment

• Patients with small primary tumors, particularly younger patients in whom extensive surgical resection may result in significant psychological consequences.

Locally advanced disease

• Patients with unresectable locally advanced disease.

Adjuvant treatment

• Following surgery to treat pelvic and groin lymph nodes.

• Following surgery in patients with positive surgical margins.

Palliative treatment

Radiotherapy may be used for symptom relief in patients with advanced disease, including:

• Pain control.

• Control of bleeding.

• Palliation of other tumor-related symptoms.

Pharmacological treatment

Chemotherapy may be administered as a radiosensitizer during radiotherapy or for palliative treatment in recurrent, persistent, metastatic, or advanced disease.

Concurrent chemoradiotherapy

Cisplatin

• 40 mg/m² intravenously once weekly during radiation therapy.

• Maximum dose: 70 mg weekly.

For patients with HIV infection or mild renal impairment:

Cisplatin

• 30 mg/m² intravenously once weekly during radiation therapy.

• Maximum dose: 60 mg weekly.

Palliative chemotherapy options

For metastatic, recurrent, or persistent disease, the following agents may be used as single agents or in combination regimens:

• Cisplatin.

• Paclitaxel.

• Bevacizumab.

• Carboplatin.

• Docetaxel.

• Gemcitabine.

Monitoring during chemotherapy

Before each chemotherapy cycle:

• Full blood count (FBC).

• Urea.

• Creatinine.

Management according to underlying cause

HPV-associated disease

• Management according to stage and extent of disease.

• Evaluation for associated cervical and vaginal lesions.

HIV-associated disease

• Management according to stage and extent of disease.

• Careful assessment of immune status and treatment tolerance.

Referral

Refer all patients with suspected or confirmed vulvar cancer to a gynecologist or specialized cancer treatment center for definitive management.

Urgent referral is required for:

• Histologically confirmed vulvar cancer.

• Enlarging vulvar masses.

• Non-healing vulvar ulcers.

• Locally advanced disease.

• Regional lymph node involvement.

• Recurrent disease.

Complications

• Local tissue destruction.

• Chronic pain.

• Secondary infection.

• Persistent ulceration.

• Lymph node metastasis.

• Distant metastasis.

• Recurrence after treatment.

• Psychological distress.

• Treatment-related complications.

• Death.

Prognosis

Prognosis depends on disease stage, lymph node involvement, histological subtype, and response to treatment. Early-stage disease managed appropriately with surgery has a favorable prognosis, whereas advanced disease with nodal or distant metastasis is associated with poorer outcomes.

Prevention

• Prevention of HPV infection.

• HPV vaccination.

• Smoking cessation.

• HIV prevention and treatment.

• Early diagnosis and treatment of vulvar intraepithelial neoplasia.

• Regular gynecological evaluation of persistent vulvar lesions.

• Prompt biopsy of suspicious vulvar lesions.

Follow-up

Patients should undergo regular follow-up to assess:

• Local recurrence.

• Regional lymph node recurrence.

• Treatment-related complications.

• Development of additional lower genital tract neoplasia.

Follow-up schedules should be individualized according to disease stage and treatment received.