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Vulvar cancer

Vulvar cancer is typically squamous cell cancer, most often occurring in older women. It usually manifests as a palpable lesion. The diagnosis is made by biopsy. Treatment typically includes surgical excision and lymph node dissection or sentinel lymph node mapping.

Vulvar cancer is the 4th most common gynecologic cancer in the United States; it represents 6% of tumors of the female genital tract. In the United States, vulvar cancer will cause an estimated 6,330 new cases and 1,560 deaths in 2022 ( 1 ).

The mean age at diagnosis is about 70; the incidence increases with age.

Vulvar cancer frequently occurs in the labia majora. Less often, vulvar cancer affects the labia minora, clitoris, or vaginal glands. Vulvar cancer usually develops slowly over several years. Precancerous cellular changes can develop on the surface of the vulvar epithelium (without invasion) over a long period of time. This condition (called vulvar intraepithelial neoplasia) can become invasive (cancerous) and therefore needs to be diagnosed and treated.

Risk factors for vulvar cancer include

• Human papillomavirus infection
• Vulvar intraepithelial neoplasia
• Cigarette smoke
• Lichen sclerosis
• Immunodeficiency
• Squamous hyperplasia
• Squamous cell carcinoma or intraepithelial neoplasia of the vagina, cervix, or anus
• Chronic granulomatous disease

Most vulvar cancers are caused by persistent human papillomavirus infection . The precursor to vulvar cancer is vulvar intraepithelial neoplasia.

General reference

• 1. American Cancer Society : Key Statistics for Vulvar Cancer. Accessed 6/21/22.

Pathology of vulvar cancer

About 90% of vulvar cancers are squamous cell carcinomas; about 5% are melanomas. Others include adenocarcinomas and transitional cell tumors, adenoid cystic carcinoma and adenosquamous carcinoma; all can originate from Bartholin’s glands. Basal cell carcinomas and sarcomas underlying an adenocarcinoma may also be found.

Vulvar cancer can spread as follows:

• By direct spread (eg, into the urethra, bladder, vagina, perineum, anus, or rectum)
• Hematogenous
• To the inguinal lymph nodes
• From inguinal lymph nodes to pelvic and para-aortic lymph nodes

Vulvar cancer diagnosis

• Biopsy

Vulvar cancer may mimic sexually transmitted genital ulcers (eg, chancroid ), basal cell carcinoma , vulvar Paget disease (pale eczematoid lesion), a Bartholin’s gland abscess or cyst , or condyloma acuminatum (genital warts) . Doctors should consider vulvar cancer if a vulvar lesion develops in women at low risk of sexually transmitted infections or if they do not respond to treatment for sexually transmitted infections.

A punch biopsy of the dermis using a local anesthetic is usually diagnostic. Occasionally, wide local excision is required to differentiate vulvar intraepithelial neoplasia from a tumor. Minimal lesions can be delineated by staining the vulva with toluidine blue or by using colposcopy.::

Staging

Staging of vulvar cancer is based on tumor size and location and spread to regional lymph nodes as evidenced by lymph node dissection or sentinel node biopsy done as part of initial surgical treatment (see table Staging of Vulvar Cancer ) .

Vulvar cancer prognosis

The 5-year overall survival rate is about 70%. The risk of spread to lymph nodes is proportional to the size of the tumor and the depth of invasion. Melanomas metastasize often, mainly based on the depth of invasion but also on the size of the tumor.

Treatment of vulvar cancer

• Wide excision and lymph node dissection except when stromal invasion is ≤ 1 mm
• Surgery, radiation and/or chemotherapy for stage III or IV cancer

(See also National Comprehensive Cancer Network (NCCN) : NCCN Clinical Practice Guidelines in Oncology: Vulvar Cancer [Squamous Cell Carcinoma].)

Wide radical excision ( ≥ 2-cm margin) of the local tumor is indicated when the tumor is confined to the vulva without extending to adjacent perineal structures. Lymph node dissection can be done when stromal invasion is > 1 mm, but is unnecessary when stromal invasion is ≤ 1 mm. Radical vulvectomy is usually reserved for adenocarcinoma of the Bartholin gland.

For lateralized lesions ≤ 2 cm, unilateral wide local resection and unilateral sentinel lymph node dissection are recommended. Lesions adjacent to the midline and most lesions > 2 cm require bilateral sentinel lymph node dissection.

For tumors with extension to adjacent perineal structures such as the urethra, vagina, or anus, a modified radical vulvectomy is indicated regardless of tumor size.

Sentinel node biopsy is a reasonable alternative to lymph node dissection for some women with vulvar squamous cell carcinoma. Sentinel node mapping should not be considered if clinical findings suggest that the cancer has spread to the inguinal lymph nodes. For sentinel node mapping, a tracer (blue dye, technetium-99 [ ⁹⁹ Tc], indocyanine green) is injected intradermally around and in front of the anterior border of the vulvar carcinoma.

Further lymph node evaluation and treatment are based on the results of sentinel node biopsy or lymph node dissection. If the inguinofemoral lymph nodes are negative, observation is reasonable. If one or more sentinel lymph nodes are positive, treatment depends on the size of the metastases. For micrometastases (≤ 2 mm), inguinofemoral radiation therapy (50 Gy) is a safe alternative to inguinal lymphadenectomy. For macrometastases in a sentinel node, inguinal lymphadenectomy is performed to prevent isolated groin recurrence ( 1 ).

For stage III, lymph node dissection is usually done before radical excision followed by postoperative external beam radiation and chemotherapy (chemoradiotherapy), preferably cisplatin; possibly fluorouracil. The alternative is radical or voiding surgery.

For stage IV, treatment is a combination of pelvic emptying, radiation therapy, and systemic chemotherapy (cisplatin, carboplatin, cisplatin, or carboplatin/paclitaxel, or cisplatin/paclitaxel plus bevacizumab).

Treatment reference

• 1. Oonk MHM, Slomovitz B, Baldwin PJW, et al : Radiotherapy versus inguinofemoral lymphadenectomy as treatment for vulvar cancer patients with micrometastases in the sentinel node:

Key points

• Most vulvar cancers are squamous cell carcinomas; about 5% are melanomas.
• Consider vulvar cancers if vulvar lesions, including itchy lesions and ulcers, do not respond to treatment for STIs or if the lesions occur in women at low risk for STIs.
• Diagnose vulvar cancer by biopsy, and stage it surgically.
• For tumors without distant metastases, use wide local excision, unless stromal invasion is < 1 mm, do lymph node dissection or sentinel node biopsy.
• For tumors with lymph nodes or distant metastases, treat with a combination of surgery, radiation therapy, and/or chemotherapy.

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