What is vulval cancer?
Vulval (vulvar) cancer is any malignancy arising on any part of the vulva, the external female genitalia. It is the fourth most common location for a gynaecological malignancy after the uterus, ovary, and cervix, accounting for 3–5% of female genital tract malignancies.
Over 80% of vulval cancers are squamous cell carcinomas (SCC) including both precursor lesions and invasive disease. Melanoma and basal cell carcinoma (BCC) are the next most common types of vulval cancer.
Uncommon causes of vulval cancer include:
- Extramammary Paget disease (EMPD)
- Bartholin gland carcinoma.
The pathogenesis, epidemiology, clinical features, and specific treatment options for each of these are covered in more detail below.
Rare vulval cancers that will not be covered in any further detail here include:
- Vulval verrucous carcinoma
- Adenocarcinoma, including sweat or sebaceous gland types
- Soft tissue tumours, such as leiomyosarcoma
- Neuroendocrine tumours, including Merkel cell carcinoma.
Metastases from non-vulval primary malignancies may present as progressively enlarging vulval nodules, e.g. breast, cervix, ovary, endometrium, kidney, and colon.
How does vulval cancer present?
Vulval cancer is often asymptomatic and found incidentally on examination or as a lump noticed on wiping.
Symptoms can be nonspecific and may indicate late disease. These include:
- Itch, burning, or pain
- Crusting, weeping, or bleeding.
What is the differential diagnosis of vulval cancer?
- Viral wart, seborrheic keratosis
- Vulval cyst or abscess
- Inflammatory dermatoses including flexural psoriasis or flexural candidiasis
- Benign melanocytic naevus
What are the complications of vulval cancer?
- Locally advanced disease may be unresectable.
- Regional or distant metastases with poor prognosis.
- Psychosexual dysfunction following treatment.
How is vulval cancer diagnosed and staged?
Routine examination of the vulva during a skin check or gynaecological examination may detect a suspicious lesion the patient is unaware of.
Vulval cancers can only be diagnosed on biopsy.
Clinical examination may need to include general skin examination, palpation of regional lymph nodes, pelvic examination, cystoscopy, proctoscopy, and/or colposcopy with cervical cytology.
Further investigations may be required to stage the disease:
- Fine needle aspirate of lymph node
- Sentinel lymph node biopsy (SNB)
- Radiology/imaging may include CT of abdomen and/or pelvis, MRI, or PET-CT.
How is vulval cancer treated?
Vulval cancers are usually treated by surgical excision, local or radical, with or without lymph node removal, and psychosexual support.
Vulval cancer requires regular careful follow-up as recurrence is common.
Vulval squamous cell carcinoma
Who gets vulval SCC?
Vulval squamous cell carcinoma has a reported annual incidence of 2–7 cases per 100,000 women. Although it was regarded as a disease of postmenopausal women with a median age at diagnosis of 69 years in the USA, over the past forty years the incidence has increased markedly in women under 50 years of age. This is probably due to a change in sexual habits and increased exposure to human papillomavirus (HPV).
Vulval SCC risk increases with:
- Multiple sexual partners
What causes vulval SCC?
The precursor lesion for vulval SCC is vulval intraepithelial neoplasia (VIN) which can be classified as:
- Vulval high-grade squamous intraepithelial lesion (HSIL, formerly called usual type VIN) — associated with HPV 16, 18, and 33 in women aged 20–40 years [see Sexually acquired human papillomavirus]. Vulval HSIL now accounts for 40–60% of cases of vulval SCC.
- Differentiated VIN — associated with chronic dermatoses such as lichen sclerosus in postmenopausal women.
What are the clinical features of vulval SCC?
- Signs — skin-coloured, white, red, or pigmented; scaly patch, plaque, ulcer, or mass; often multifocal.
Staging of vulval SCC
Table 1: 2021 FIGO staging of vulval carcinoma
Tumour confined to the vulva
IA: Tumour size ≤2 cm and stromal invasion ≤1 mma
IB: Tumour size >2 cm or stromal invasion >1 mma
|II||Tumour of any size with extension to lower one-third of urethra, lower one-third of vagina, or lower one-third of anus, with negative lymph nodes|
Tumour of any size with extension to upper part of adjacent perineal structures, or with any number of non-fixed, nonulcerated lymph nodes
IIIA: disease extension to upper two-thirds of urethra or vagina, bladder or rectal mucosa, or regional nodesb ≤5 mm
IIIB: regional lymph nodesb >5mm
IIIC: regional lymph nodeb metastases with extracapsular spread
Tumour of any size fixed to bone, or fixed ulcerated lymph node metastases, or distant metastases
IVA: disease fixed to pelvic bone or fixed or ulcerated regional lymph node metastases
IVB: distant metastases
a depth of invasion is measured from the basement membrane of the deepest adjacent tumour-free rete ridge to the deepest point of invasion.
b regional lymph nodes refers to inguinal and femoral lymph nodes.
What is the treatment for vulval SCC?
- HPV vaccination introduced as a primary prevention strategy for cervical cancer is showing a promising reduction in HPV-related VIN and vulval SCC.
- Treatment of precursor lesions — see Vulval intraepithelial neoplasia.
- Wide local surgical excision where possible. For early disease, local excision has the same survival outcome as radical vulvectomy.
- SNB and/or lymph node removal may be indicated.
- Advanced disease may require chemoradiotherapy (eg, electron beam radiotherapy + cisplatin) or palliative radiotherapy.
- Targeted therapies such as immune checkpoint inhibitors are being explored for advanced, metastatic, and recurrent disease.
What is the outcome for vulval SCC?
Vulval HSIL tends to be slow-growing with spontaneous regression in some cases. Differentiated VIN rapidly progresses to invasive SCC with a high recurrence rate and worse prognosis. Vulval SCC presents with locally advanced disease in 30% of cases which may be unresectable. The 5-year recurrence rate is 37%. Prognosis is poor with lymph node or distant metastases.
Who gets vulval melanoma?
Vulval melanoma accounts for 5–10% of all vulval cancers and 2% of all melanomas in women. The vulva is at a higher risk of developing melanoma than the skin elsewhere. The reported incidence is <0.2 cases/100,000 women with a wide reported age range of 10–107 years, predominantly in white women aged 40–60 years.
What causes vulval melanoma?
- Distinct from other mucosal melanomas
- Unrelated to sun or ultraviolet (UV) exposure
- Unlike cutaneous melanoma, BRAF mutations are found in less than 25% of lesions and c-KIT mutations are more common
What are the clinical features of vulval melanoma?
- Signs — irregular pigmented macule, papule or nodule on the labia majora or clitoris; often amelanotic (25%) especially on the vulval mucosa; over 50% are lentiginous type, and 22% are nodular.
- Dermoscopy — polymorphous vessels, structureless zones, multiple colours including blue, grey, or white, peripheral radial lines, thick reticular lines.
How is vulval melanoma staged?
Vulval melanoma should be staged using the AJCC system.
What is the treatment for vulval melanoma?
- Vulval melanoma should ideally be excised with the same margin rules as cutaneous melanoma, but this is often not feasible.
- Local excision has fewer complications than radical vulvectomy with a similar outcome.
- SNB should be offered.
- Immune checkpoint inhibitors or tyrosine kinase inhibitors may be considered if appropriate.
What is the outcome for vulval melanoma?
Vulval melanoma diagnosis is often delayed and is clinically aggressive with one-third having regional and/or distant metastases at presentation. Median survival is approximately 50 months and five-year survival less than 50% (compared to cutaneous melanoma 92%) due to late presentation, different tumour biology, and approach to treatment.
Vulval basal cell carcinoma
Who gets vulval BCC?
Vulval basal cell carcinoma is typically diagnosed in white women aged 60–80 years (mean 70 years).
Multiple lesions are associated with basal cell naevus syndrome (BCNS).
What causes vulval BCC?
- No precursor lesion
- Not associated with sun or UV exposure
- Pathogenesis may include immunosuppression, chronic irritation, pelvic radiation, trauma
What are the clinical features of vulval BCC?
- Signs — solitary lesion usually nodular type on the labia majora; shiny indurated well-demarcated papule or plaque 0.5–5cm in diameter; pigmentation common in Asian women.
- Dermoscopy — typical features of nodular BCC.
What is the treatment for vulval BCC?
- Local surgical excision or Mohs micrographic surgery without lymph node biopsy
- Other — topical imiquimod, topical 5-fluorouracil, photodynamic therapy (PDT).
What is the outcome for vulval BCC?
Vulval basal cell carcinoma is typically slow-growing with a low risk of metastasis. Local invasion can occur if untreated resulting in tissue destruction.
Vulval extramammary Paget disease
Who gets vulval EMPD?
The vulva is the commonest site for EMPD (65%) and typically affects Caucasian postmenopausal women (median age 72 years).
What causes vulval EMPD?
- Primary EMPD — de novo adenocarcinoma within the vulval epithelium
- Secondary EMPD — associated with an anorectal or urethral neoplasm
What are the clinical features of vulval EMPD?
- Symptoms — often longstanding itch and/or pain
- Signs — asymmetrical circumscribed scaly/crusted plaque; patchy/multifocal; red, hypopigmented, hyperpigmented
How is vulval EMPD diagnosed and staged?
Vulval EMPD often requires multiple biopsies to make the diagnosis and classify as:
- In situ
- Micro-invasive — depth of invasion 0.1mm or less
- Invasive — depth of invasion >0.1mm.
What is the treatment for vulval EMPD?
- Surgical excision — local, wide, or Mohs micrographic surgery, although margins are often positive.
- Other — topical imiquimod, photodynamic therapy, radiotherapy.
What is the outcome for vulval EMPD?
Vulval EMPD typically follows an indolent course with a good prognosis although diagnosis is often late and recurrence is common. Invasive vulval EMPD has a worse prognosis than in situ disease.
Bartholin gland carcinoma
Who gets Bartholin gland carcinoma?
Bartholin gland carcinoma is a rare cause of vulval cancer (2–7%) presenting in women aged 40–50 years.
What are the clinical features of Bartholin gland carcinoma?
- Symptoms — painless mass
- Signs — visible tumour on posterior half of the vulva
How is Bartholin gland carcinoma diagnosed and staged?
- FIGO staging (see Table 1)
What is the treatment for Bartholin gland carcinoma?
- Radical local excision with SNB or lymph node dissection
- Follow-up radiotherapy
What is the outcome for Bartholin gland carcinoma?
Bartholin gland carcinoma recurs following surgery in one-third of cases. Prognosis depends on the FIGO stage.