Vulvar cancer

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. • Skin changes in the vulva, including what looks like 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. Typically, a lesion 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. Due to modesty or embarrassment, people may put off seeing a doctor. Melanomas tend to display the typical asymmetry, uneven borders, and dark discoloration, as do melanomas in other parts of the body. Adenocarcinoma can arise from the Bartholin's gland and present with a painful lump. == Causes ==

Two main pathophysiological pathways are currently understood to contribute to the development of vulvar cancer: 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 in VIN and vulvar cancer, followed by HPV 33 and HPV 18. VIN is a superficial lesion of the skin that has not invaded the basement membrane—or a pre-cancer. VIN may progress to carcinoma in situ and, eventually, squamous cell cancer. Chronic inflammatory conditions of the vulva that may be precursors to vulvar cancer include lichen sclerosus, which can predispose to differentiated VIN. Risk factors Risk factors for vulvar cancer are largely related to the causal pathways above, involving exposure or infection with the HPV virus and/or acquired or innate autoimmunity. • Increasing age • History of vulvar or cervical intraepithelial neoplasia • Increased number of male sexual partners • Prior history of 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 is part of the gynecologic evaluation. It should include a thorough inspection of the perineum, including areas around the clitoris and urethra, and palpation of the Bartholin's glands. The exam may reveal an ulceration, lump, or mass in the vulvar region. Any suspicious lesions need to be sampled, or biopsied. This can generally be done in an office setting under local anesthesia. Small lesions can be removed under local anesthesia. Additional evaluation may include a chest X-ray, an intravenous pyelogram, cystoscopy or proctoscopy, as well as blood counts and metabolic assessment. Types Depending on the cellular origin, different histologic cancer subtypes may arise in vulvar structures. Squamous cell carcinoma A recent analysis of the Surveillance, Epidemiology and End Results (SEER) registry of the US National Cancer Institute has shown that squamous cell carcinoma accounts for approximately 75% of all vulvar cancers. They 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. Basal cell carcinoma Basal cell carcinoma accounts for approximately 8% of all vulvar cancers. It typically affects women in the 7th and 8th decades of life. The underlying biology of vulvar melanoma differs significantly from skin melanomas, and mutational analyses have shown that only 8% harbor a BRAF mutation compared to 70% of skin melanomas. KIT mutations, however are significantly more common in vulvar melanoma. In recurrent melanoma, tyrosine kinase inhibitors may be used in those patients with a KIT mutation. Diagnosis of vulvar melanoma is often delayed, and approximately 32% of women already have regional lymph node involvement or distant metastases at the time of diagnosis. Staging Anatomical staging supplemented preclinical staging starting in 1988. 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 the inguinal lymph nodes on both sides or distant metastases. {{#tag:gallery File:Diagram showing stage 2 cancer of the vulva CRUK 205.svgStage 2 vulvar cancer File:Diagram showing stage 3 cancer of the vulva CRUK 219.svgStage 3 vulvar cancer File:Diagram showing stage 4A cancer of the vulva CRUK 235.svgStage 4A vulvar cancer File:Diagram showing stage 4B cancer of the vulva CRUK 238.svgStage 4B vulvar cancer Differential diagnosis Other cancerous lesions in the differential diagnosis include Paget's disease of the vulva and vulvar intraepithelial neoplasia (VIN). Non-cancerous vulvar diseases include lichen sclerosus, squamous cell hyperplasia, and vulvar vestibulitis. A number of diseases cause infectious lesions including herpes genitalis, human papillomavirus, syphilis, chancroid, granuloma inguinale, and lymphogranuloma venereum. == Treatment ==

Surgery is a mainstay of therapy, depending on anatomical staging, and is usually reserved for cancers that have not spread beyond the vulva. Sentinel lymph node (SLN) dissection is a technique used to identify the main lymph node(s) draining the tumor. The goal is to remove as few lymph nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only. Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy. Checkpoint inhibitors may be given in melanoma of the vulva. There is no significant difference in overall survival or treatment‐related adverse effects in women with locally advanced vulval cancer when comparing primary chemoradiation or neoadjuvant chemoradiation with primary surgery. There is a need for good-quality studies comparing various primary treatments. Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every three months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs. == Prognosis ==

Overall, five-year survival rates for vulvar cancer are around 78% Prognosis depends on the stage of cancer, which refers to the amount and spread of cancer in the body. "Localized," is when the cancer is limited to one part of the body. This has the highest survival rate, 86% in the United States. When the cancer starts to spread, this is referred to as "regional"; this stage usually involves the cancer spreading to the lymph nodes. This survival rate is 50%. When the cancer has metastasized and spread throughout the body, the survival rate is 22%. ==Epidemiology==

Vulvar cancer newly affected about 44,200 people and resulted in 15,200 deaths globally in 2018. This is most common in younger women, predominantly under the age of 40. In the United Kingdom, 7 out of 10 vulval cancer patients have major surgical resection as part of their cancer treatment. 22% of patients use radiotherapy and only 7% use chemotherapy as a treatment plan. Vulvar cancer cases have been rising in the United States at an increase of 0.7% each year over the 2013-2022 period. ==See also==