Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals.
It most commonly affects the labia majora, and less often, the labia minora, clitoris, or Bartholin’s glands.
Accounts for 5% of all female genital cancers and 1% of all malignancies in women.
2500 cases per year and 500 deaths per year in the U.S.
Vulvar cancer symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.
Occurs after the age of 45.
Tissue types: Squamous cell cancer, adenocarcinoma, melanoma, sarcoma, basal cell carcinoma.
Risk factors: Vulvar intraepithelial neoplasia (VIN), HPV infection, genital warts, smoking, many sexual partners.
Differential diagnosis Lichen sclerosus, hyperplasia
Prevention HPV vaccination
Treatment
Surgery, radiation therapy, chemotherapy, biologic therapy
Prognosis
Five-year survival ~ 71%
Frequency 44,200 globally
Deaths 15,200 (2018) globally
Risk factors include vulvar intraepithelial neoplasia (VIN), HPV infection, genital warts, smoking, and many sexual partners.
Most vulvar cancers are squamous cell cancers, but other types include adenocarcinoma, melanoma, sarcoma, and basal cell carcinoma.
Diagnosis is suspected based on physical examination and confirmed by tissue biopsy.
Standard treatments may include surgery, radiation therapy, chemotherapy, and biologic therapy..
In the United States, there are about 6,070 people with 1,280 deaths a year.
Onset is typically after the age of 45.
Outcomes, are affected by spread to lymph nodes.
The signs and symptoms can include: Itching, burn, or bleeding on the vulva that does not go away, changes in the color of the skin of the vulva, so that it looks redder or whiter than is normal, a rash or warts, Sores, lumps, or ulcers on the vulva that do not go away.
Pain in the pelvis, especially during urination or sex, may occur.
Typically, lesions presents in the form of a lump or ulcer on the labia majora and may be associated with itching, irritation, local bleeding or discharge, in addition to pain with urination or pain during sexual intercourse.
The labia minora, clitoris, perineum and mons pubis are less commonly involved with vulvar carcinoma.
Two main pathophysiological pathways: human papillomavirus (HPV) infection and chronic inflammation or autoimmunity affecting the vulvar area.
HPV DNA can be found in up to 87% of vulvar intraepithelial neoplasia (VIN) and 29% of invasive vulvar cancers.
HPV 16 is the most commonly detected subtype, followed by HPV 33 and HPV 18.
Chronic inflammatory conditions of the vulva that may be precursors to vulvar cancer: lichen sclerosus.
Risk factors for vulvar cancer involving exposure or infection with the HPV virus and/or acquired or innate auto-immunity.
Increasing age
History of vulvar or cervical intraepithelial neoplasia
Increased number of male sexual partners
Prior history pre-invasive or invasive cervical cancer
History of cigarette smoking
Infection with human immunodeficiency virus (HIV)
Vulvar lichen sclerosus
Immunodeficiency syndromes
Northern European ancestry
Diagnosis
Examination of the vulva includes a thorough inspection of the perineum, including areas around the clitoris and urethra, and palpation of the Bartholin’s glands.
Examination may reveal ulceration, a lump or mass in the vulvar region.
Suspicious lesions are biopsied.
Additional evaluation may include a chest X-ray,cystoscopy or proctoscopy, CT imaging as well as blood counts and metabolic assessment.
Different histologic cancer subtypes may arise in vulvar structures.
Squamous cell carcinoma: accounts for approximately 75% of all vulvar cancers, originating from epidermal squamous cells.
Carcinoma-in-situ is a precursor lesion of squamous cell cancer that does not invade through the basement membrane.
There are two types of precursor lesions: Usual-type vulvar intraepithelial neoplasia, associated with human papillomavirus (HPV) and often affects younger women.
This precursor lesion progresses to squamous cell carcinoma in approximately 6%.
Differentiated vulvar intraepithelial neoplasia is associated with chronic skin conditions including lichen sclerosus and lichen planus and typically affects older women.
This lesion progresses to keratinizing squamous cell carcinoma in approximately 33%.
Squamous cancer lesions tend to arise in a single site and occur most commonly in the vestibule.and grow by local extension and spread via the local lymph system.
The lymphatics of the labia drain to the upper vulva and mons pubis, then to both superficial and deep inguinal and femoral lymph nodes.
The last deep femoral node is called the Cloquet’s node, and spread beyond this node reaches the lymph nodes of the pelvis.
The vulvar tumor may also invade nearby organs such as the vagina, urethra, and rectum and spread via their lymphatics.
A rare subtype of squamous cell cancer, verrucous carcinoma, tends to appear as a slowly growing, and tends to have a good overall prognosis, as these lesions hardly ever spread to regional lymph nodes or metastasize.
Basal cell carcinoma account for approximately 8% of all vulvar cancers.
Basal cell carcinoma of the vulva typically affects women in the 7th and 8th decade of life.
These tend to be slow-growing lesions on the labia majora but can occur anywhere on the vulva.
Melanoma is the third most common type and accounts for 6% of all vulvar cancers. These lesions arise from melanocytes, the cells, with a median age at diagnosis is 68 years.
The underlying biology of vulvar melanoma differs significantly from skin melanomas and mutational analyses have shown only 8% harbor a BRAF mutation compared to 70% of skin melanomas.
KIT mutations, however are significantly more common in vulvar melanoma.
BRAF-inhibitors that are commonly used in the treatment of skin melanomas, but play a minor role in vulvar melanomas.
Vulvar melanomas frequently express PD-L1 and checkpoint inhibitors and are effective in the treatment of advanced-stage vulvar melanoma.
In recurrent melanoma, tyrosine kinase inhibitors may be used in those patients with a KIT mutation.
Based on histology, there are different subtypes of vulvar melanoma: superficial spreading, nodular, acral lentigous and amelanotic melanoma.
Diagnosis of vulvar melanoma is often delayed.
Approximately 32% of women have regional lymph node involvement or distant metastases at the time of diagnosis of vulvar melanoma.
The overall prognosis of vulva melanoma is poor and significantly worse than in skin melanomas: The median overall survival is 53 months.
The Bartholin gland is a rare malignancy and usually occurs in women in their mid-sixties.
Other forms of vulvar cancer include invasive Extramammary Paget’s disease, adenocarcinoma (of the Bartholin glands, and sarcoma.
FIGO’s revised TNM classification system uses tumor size (T), lymph node involvement (N) and presence or absence of metastasis (M) as criteria for staging.
Stages I and II describe the early stages of vulvar cancer that still appear to be confined to the site of origin.
Stage III cancers include greater disease extension to neighboring tissues and inguinal lymph nodes on one side.
Stage IV indicates metastatic disease to inguinal nodes on both sides or distant metastases.
A number of diseases cause infectious lesions including herpes genitalis, human papillomavirus, syphilis, chancroid, granuloma inguinale, and lymphogranuloma venereum.
Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva.
Surgery may involve a wide local excision, radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes.
In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy.
Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum.
Complications of vulvar surgery include: wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.
Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects.
Radiation therapy before or after surgery may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis.
Chemotherapy is not usually used as primary treatment but may be used in advanced cases with metastases.
It may also be given with radiation therapy.
Checkpoint inhibitors may be given in melanoma of the vulva.
Overall, five-year survival rates for vulvar cancer are around 78%: affected by individual factors including cancer stage, cancer type, patient age and general medical health.
Five-year survival is greater than 90% for patients with stage I lesions but decreases to 20% when pelvic lymph nodes are involved.
Lymph node involvement is the most important predictor of prognosis.
Prognosis depends on the stage of cancer.
Vulvar cancer can be split up into two types: infection by human papillomavirus, which leads to vulvar intraepithelial neoplasia (VIN) and potentially on to vulvar cancer.
HPV associated vulvar carcinoma is most common in younger women, predominantly under the age of 40.
The second type is vulvar non-neoplastic epithelial disorders, most common in older women, due to the increased risk for developing cellular atypia which in turn leads to cancer.
In the United States, is newly diagnosed in about 6,070 people with 1,280 deaths a year.
It makes up about 0.3% of new cancer cases, and 5% of gynecologic cancers in the United States.
Vulvar cancer cases have been rising in the United States at an increase of 0.6% each year for the past ten years.
Any vulvar lesion discovered by a physical examination should be biopsied to rule out a neoplasm.
Most vulvar neoplasia are diagnosed in early stages.
Histology include melanoma, extramammary Paget’s, disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, with most cases being squamous cell carcinoma.
Approximately 39% of patients with vulvar cancer are diagnosed with advanced stages III or IV.
87% of lesions are squamous cancers and 6% are malignant melanoma.
Incidence of squamous cell vulvar cancer 2.5 per 100,000 women.
Risk factors include: increasing age, infection with HPV, cigarette smoking, inflammatory conditions affecting the vulva and immunodeficiency.
Standard treatment for early stage squamous cell carcinoma is wide local excision and unilateral or bilateral inguinofemoral lymphadenectomy.
In locally advanced vulvar cancers, preoperative chemoradiation is delivered.
The most common agents used for preoperative chemotherapy/radiation include cisplatinum, fluorouracil, and Mitomycin C.
Well significant prognostic factor for vulvar squamous cell carcinoma is lymph node status.
Factors associated with poor outcomes besides lymph nodes status include age, tumor diameter, tumor depth, tumor class, histologic grade, lymphovascular space invasion, margin distance, and clitoral involvement.
Half a women who undergo surgical treatment for vulvar cancer have wound complications.
Lymphedema and cellulitis following lymphadenectomy, can be lifelong issues.
Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected patients.
Studies have demonstrated a superiority of groin and pelvic radiotherapy compared to pelvic lymphadenectomy in patients undergoing radical pelvic vulvectomy with groin metastases.
Locally advanced vulvar tumors that are unresectable without removing the proximal urethra/bladder/anus should undergo external beam radiation with concurrent chemotherapy: inguinal femoral lymphadenectomy may be required, if abnormal radiographic nodal studies are present.
Adjuvant chemoradiation therapy is recommended for patients with nodal disease.
Most recurrences of vulvar cancer occur within the first one to two years.
Among patients with recurrence about 37% develop recurrent vulvar squamous cell carcinoma.
Over half of recurrences are vulvar followed by inguinal at 18.7%, multisite at 14.2%, distant at 7.9% and pelvic at 5.7%.
Survival at five years is 60% for vulvar recurrences, 27% for inguinal/pelvic and 15% distant sites and 14% from multiple sites.
No clear standard of care exists for recurrent vulvar carcinoma with treatment and outcome, depending on the site and extent of recurrent disease.
Treatment options include surgery, radiation, chemotherapy, and checkpoint inhibitors.