Vulvar cancer is the 4th most common gynecologic cancer in the US; it accounts for 6% of cancers of the female genital tract. In the US, vulvar cancer will cause an estimated 6330 new cases and 1560 deaths in 2022 (1 General reference Vulvar cancer is usually a squamous cell cancer, most often occurring in older women. It usually manifests as a palpable lesion. Diagnosis is by biopsy. Treatment typically includes excision... read more ).
Median age at diagnosis is about 70 years; 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 a number of years. Precancer 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 [VIN]) can become invasive (cancerous) and so should be diagnosed and treated.
Risk factors for vulvar cancer include
Vulvar intraepithelial neoplasia (VIN)
Cigarette smoking
Immunodeficiency
Squamous hyperplasia
Squamous carcinoma or intraepithelial neoplasia of the vagina, cervix, or anus
Most vulvar cancers are caused by persistent human papillomavirus (HPV) infection Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more 
. The precursor to vulvar cancer is vulvar intraepithelial neoplasia (VIN).
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, adenoid cystic, and adenosquamous carcinomas; all may originate in Bartholin glands. Sarcomas and basal cell carcinomas with underlying adenocarcinoma also occur.
Vulvar cancer may spread as follows:
By direct extension (eg, into the urethra, bladder, vagina, perineum, anus, or rectum)
Hematogenously
To the inguinal lymph nodes
From the inguinal lymph nodes to the pelvic and para-aortic lymph nodes
Diagnosis of Vulvar Cancer
Biopsy
Vulvar cancer may mimic sexually transmitted genital ulcers (eg, chancroid Chancroid Chancroid is infection of the genital skin or mucous membranes caused by Haemophilus ducreyi and characterized by papules, painful ulcers, and enlargement of the inguinal lymph nodes... read more 
), basal cell carcinoma Basal Cell Carcinoma Basal cell carcinoma is a superficial, slowly growing papule or nodule that derives from certain epidermal cells. Basal cell carcinomas arise from keratinocytes near the basal layer, which are... read more 
, vulvar Paget disease (a pale eczematoid lesion), Bartholin gland cyst Bartholin Gland Cyst and Bartholin Gland Abscess Bartholin gland cysts are the most common large vulvar cysts. They are mucus-filled and are located on either side of the vaginal opening. Symptoms of large cysts include vulvar pressure or... read more 
or abscess, or condyloma acuminatum (genital wart) Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more . Clinicians should consider vulvar cancer if a vulvar lesion develops in women at low risk of sexually transmitted infections (STIs) or if it does not respond to treatment for STIs.
A dermal punch biopsy using a local anesthetic is usually diagnostic. Occasionally, wide local excision is necessary to differentiate VIN from cancer. Subtle lesions may 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 on regional lymph node spread as determined by lymph node dissection or sentinel lymph node (SLN) biopsy done as part of initial surgical treatment (see table Vulvar Cancer by Stage Vulvar Cancer by Stage 
).
Prognosis for Vulvar Cancer
Overall 5-year survival rate is about 70%. Risk of lymph node spread is proportional to the tumor size and invasion depth. Melanomas metastasize frequently, depending mostly on invasion depth but also on tumor size.
Treatment of Vulvar Cancer
Wide excision and lymph node dissection except when stromal invasion is ≤ 1 mm
Surgery, radiation therapy, 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 (≥ 2-cm margin) radical excision of the local tumor is indicated when the tumor confined to the vulva with no extension to adjacent perineal structures. Lymph node dissection may be done when stromal invasion is > 1 mm but is unnecessary when stromal invasion is ≤ 1 mm. Radical vulvectomy is usually reserved for Bartholin gland adenocarcinoma.
For lateralized lesions ≤ 2 cm, unilateral wide local excision and unilateral SLN dissection is recommended. Lesions near the midline and most lesions > 2 cm require bilateral SLN dissection.
For tumors with extension to adjacent perineal structures such as the urethra, vagina, or anus, a modified radical vulvectomy is indicated independent of tumor size.
Sentinel lymph node biopsy is a reasonable alternative to lymph node dissection for some women with squamous cell vulvar carcinoma. SLN mapping should not be considered if clinical findings suggest cancer has spread to lymph nodes in the groin. For SLN mapping, a tracer (blue dye, technetium-99 [99Tc], indocyanine green [ICG]) is injected intradermally around and in front of the leading edge of the vulvar carcinoma.
Further evaluation of lymph nodes and treatment are based on the results of SLN biopsy or lymphadenectomy. If inguinofemoral nodes are negative, observation is reasonable. If one or more SLNs are positive, treatment depends on the size of the metastasis. For micrometastases (≤ 2 mm), inguinofemoral radiotherapy (50 Gy) is a safe alternative to inguinal lymphadenectomy. For macrometastases in an SLN, inguinal lymphadenectomy is done to prevent isolated groin recurrence (1 Treatment reference Vulvar cancer is usually a squamous cell cancer, most often occurring in older women. It usually manifests as a palpable lesion. Diagnosis is by biopsy. Treatment typically includes excision... read more ).
For stage III, lymph node dissection followed by postoperative external beam radiation therapy and chemotherapy (chemoradiation)—preferably cisplatin; possibly fluorouracil—is usually done before wide radical excision. The alternative is more radical or exenterative surgery.
For stage IV, treatment is some combination of pelvic exenteration, 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: Results of GROINSS-V II. J Clin Oncol 39 (32):3623–3632, 2021. doi: 10.1200/JCO.21.00006 Epub 2021 Aug 25.
Key Points
Most vulvar cancers are squamous cell carcinomas; about 5% are melanomas.
Consider vulvar cancers if vulvar lesions, including pruritic lesions and ulcers, do not respond to treatment for STIs or the lesions occur in women at low risk of STIs.
Diagnose vulvar cancer by biopsy, and stage it surgically.
For cancers without distant metastases, use wide local excision, and unless stromal invasion is < 1 mm, do lymph node dissection or sentinel lymph node biopsy.
For cancers with lymph node or distant metastases, treat with a combination of surgery, radiation therapy, and/or chemotherapy.
More Information
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Cancer Institute: Vulvar Cancer: This web site provides links to information about causes, prevention, and treatment of vulvar cancer, as well as links to information about screening, statistics, and supportive and palliative care.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
indocyanine green |
IC Green |
cisplatin |
Platinol, Platinol -AQ |
fluorouracil |
Adrucil, Carac, Efudex, Fluoroplex, Tolak |
carboplatin |
Paraplatin |
paclitaxel |
Onxol , Taxol |
bevacizumab |
Alymsys, Avastin, MVASI, Zirabev |
