Vulvar cancer

ALSO KNOWN AS: Vulvar carcinoma

RELATED CONDITIONS: Human papillomavirus (HPV), vaginal cancer, vaginal intraepithelial neoplasia (VAIN), vulvar intraepithelial neoplasia, melanoma, squamous cell carcinoma, Paget disease, adenocarcinoma, verrucous carcinoma, basal cell carcinoma, Bowen disease

DEFINITION: Vulvar cancer is the name for malignant growths that originate from the vulva, the visible part of the female external genitalia. The vulva is the collective term for the labia majora, labia minora, clitoris, and perineum. The parts of the vulva are similar in tissue type, which suggests the cancers that can arise from them. The most common tissue type is a squamous cell, which makes up the lining of many organs, such as the skin and mucous membranes of the vagina and mouth. Squamous cell carcinoma accounts for about 90 percent of all types of vulvar cancer. Individual cells from this type of carcinoma appear flattened, immature, disordered, multilayered, and with dark-staining nuclei on light microscopy. Another common type that makes up about 5 percent of vulvar cancer patients is melanoma, which is derived from the pigment cells of the skin (melanocytes). Other, less common types include Paget disease of the vulva, sometimes associated with adenocarcinoma and verrucous, Bartholin gland, and basal cell carcinomas.

Risk factors: The risk factors for acquiring vulvar cancer include older age, tobacco use, age of first sexual intercourse less than nineteen years, having more than two sexual partners, and low socioeconomic status. Abnormal Pap smears, long-standing vulvar dystrophy associated with diabetes, a compromised immune system, exposure to herpes simplex virus 2 (HSV2), and human papillomavirus (HPV) types 16 or 18 are also risk factors. Vulvar cancer has also been associated with a prior history of cervical or vaginal cancer. Precursor lesions such as lichen sclerosis and vulvar intraepithelial neoplasia grade III may also be risk factors.

Etiology and the disease process: Like most cancers, the development of vulvar cancer is closely linked to deoxyribonucleic acid (DNA) damage and the mechanisms that regulate cell division, particularly the TP53 tumor-suppressor gene. Multiple factors contribute to the probability of inducing a cell to become cancerous. Toxic substances in cigarette smoke or replicating viral DNA spliced with cell DNA can cause damage to replicating or unwound DNA in tissue with high cell turnover and division (such as that in the skin and intestinal tract). Replication errors can also occur in aging cells.

Incidence: Vulvar cancer affects about 0.7 percent of all women and about 6 percent of cancers in the female reproductive system. More than 80 percent of individuals with vulvar cancer are over fifty. However, the proportion of vulvar cancer in women under the age of fifty increased dramatically dramatically in the late twentieth century and early twenty-first century. It more than doubled from 1980–89 to 1998–2007. In the United States, women have a 1 in 333 chance of developing vulvar cancer, with slightly less than seven thousand diagnoses annually.

Symptoms: Persistent itching of the vulva in an older woman with involvement of the surrounding skin, with or without the presence of a vulvar lesion, may be the first sign of vulvar cancer, as it is associated with increased proliferation of vulvar tissue. The itching may have been previously treated but was unsuccessful. The patient may have a wartlike lesion, lump, or an ulcer that has appeared and has been recalcitrant to treatment. A mass in or near the groin area that persists even after antibiotic treatment can be suggestive of cancer that has spread to the lymph nodes, draining the vulvar area. Many clinical situations can preclude this, including more common infectious etiologies. Physical examination of the vulva may also be nominal in early-stage vulvar cancer. However, an irregularly shaped, changing, and persistent ulcer or solid mass that may or may not be movable in the vulvar area, accompanied by a suggestive clinical history, increases the probability of cancer.

Screening and diagnosis: There is no screening test for vulvar cancer. However, if a lesion on the vulva does not respond to treatments for common etiologies, a wedge biopsy removal or punch biopsy of lesions should be performed to confirm the diagnosis. Care must be taken to ensure groin lymph nodes are truly absent, as their presence can alter disease management. Sentinel node biopsy may be performed to determine the extent to which the cancer has spread. The margin of normal tissue is necessary to assess the microscopic extent of the cancer and correctly stage the cancer. The diagnosis of vulvar cancer is confirmed when microscopic examination of the cells and tissue architecture shows changes in the characteristics of cancer cells. In addition, the gross specimen is evaluated in terms of the depth of penetration of the lesion into the stroma (underlying tissue) and its widest visible breadth.

Because of the possibility of microscopic spread to other organs, other diagnostic tests may include a cervical Pap smear, vaginal and cervical colposcopy to look for other lesions, pelvic computed tomography (CT) scan, or magnetic resonance imagery (MRI) that includes the groin area to look for enlarged lymph nodes that were missed in the physical examination, a chest X-ray, and blood tests before surgery.

The International Federation of Gynecology and Obstetrics (FIGO) uses the following surgical staging system to classify the severity of vulvar cancer by tumor size, lymph node involvement, and the presence or absence of distal metastasis:

• Stage 0: Carcinoma in situ or preinvasive carcinoma
• Stage IA: Vulvar cancer is confined to the vulva or vulva and perineum and measures 2 cm or less at greatest breadth. Stromal invasion is less than or equal to 1 mm.
• Stage IB: Vulvar cancer is confined to the vulva or vulva and perineum and measures 2 cm or greater at greatest breadth or stromal invasion is greater than 1 mm.
• Stage II: Invasive vulvar cancer has encroached into the lower urethra, vagina, or anus but has not spread to the pelvic lymph nodes.
• Stage III: Invasive vulvar cancer has encroached into the lower urethra, vagina, or anus and has spread to corresponding right- or left-draining pelvic lymph nodes.
• Stage IV: Invasive vulvar cancer has encroached into the bladder mucosa, rectal mucosa, or upper urethral mucosa or is fixed to underlying bone, involves bilateral lymph nodes, or has invaded other, distant organs starting from the pelvic lymph nodes.

Surgical staging is only complete once the furthest extent of spread is evaluated, and it does not change afterward with treatment.

Treatment and therapy: For cancer confined within the epithelium or precancerous lesions such as vulvar intraepithelial neoplasia located on the lateral aspect of the labia majora outward, local excision of the vulvar epithelium with a one-centimeter (cm) margin is warranted. Lesions of the labia minora inward may be amenable to local excision, with laser ablation as an alternative. Wide local excision is recommended for Stage IA lesions two cm or less in breadth and less than one millimeter (mm) in depth.

There are two procedures used in the treatment of vulvar cancer beyond Stage IA—wide surgical excision of the lesion, surrounding vulvae, and perineal area, and dissection and biopsy of inguinal lymph nodes at the femoral region of the thigh. During the 1960s, a conservatory approach to radical vulvectomy that involved preserving as much normal tissue as possible and separating right and left inguinal incisions to dissect lymph nodes was adopted and became the standard approach. Bulky tumors that encroach into adjacent organs preclude conservation, where diseased areas are excised while preserving functionality where feasible.

Postoperative radiation therapy may be warranted in Stage III and IV vulvar cancer if surgical intervention is insufficient to address the spread into the vagina, bladder, urethra, rectum, or microscopic spread of tumor cells to neighboring lymph nodes. Radiation therapy, often combined with chemotherapy, is also used for patients who cannot tolerate radical surgery. Common chemotherapy drugs include Cisplatin (Platinol and Platinol-AQ) and fluorouracil (Carac). Some patients are good candidates for immunotherapy drugs, like Imiquimod cream (Aldara and Zyclara).

Prognosis, prevention, and outcomes: The overall five-year survival rate of women with vulvar cancer is 70.5 percent. Earlier diagnosis means a higher survival rate—when the cancer is localized (roughly stages I to II) at diagnosis, the survival rate is 85.7 percent; regional, 53.9 percent; and distant, 15.9 percent. Positive lymph node status and larger tumor size are associated with lower survival rates.

Preventive measures include modifying risk factors and early detection of disease. Smoking cessation, safe sexual behaviors, and good hygiene are recommended. Regular Pap smears, visual inspection of the vulvar area, and biopsy of suspicious lesions are also advised. Human papillomavirus (HPV) vaccines also deter the development of precancerous lesions.

Bibliography

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Mikami, Mikami, and Mikami Mikio. Surgery for Gynecologic Cancer. Springer, 2019.

Olawaiye, Alexander B., et al. "Cancer of the Vulva: 2021 Update." International Journal of Gynecology & Obstetrics, vol. 155, 2021, pp. 7-18. doi.org/10.1002/ijgo.13881.

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