Vulval Cancer

Epidemiology

Vulvar cancer is the 4th most common gynecologic malignancy, representing ~4–6% of female genital tract malignancies and 0.6% of all cancers in women. In the US, approximately 6,020 new cases and 1,150 deaths occur annually. The overall 5-year survival is 72%. It predominantly affects postmenopausal women (most common anogenital cancer in women >70 years), though the mean age at diagnosis (~65 years) has trended downward due to rising HPV-related cases in younger women.

Age-adjusted incidence: 2.8/100,000 (white women), 1.7/100,000 (black women)
Incidence of in situ disease is increasing, driven by younger women (75% of in situ cases)

Histological Types

Type	Frequency
Squamous cell carcinoma (SCC)	>80–90%
Melanoma	~5%
Basal cell carcinoma	~2%
Adenocarcinoma / Bartholin gland carcinoma	Rare
Sarcoma	1–2%
Others (Paget disease, verrucous carcinoma, Merkel cell)	Rare

Pathogenesis: Two Distinct Pathways

1. HPV-Associated (~30–40%)

Related to high-risk HPV (principally HPV-16)
Precursor lesion: usual-type VIN (uVIN) / squamous intraepithelial lesion (SIL)
Basaloid or warty histology
Occurs in younger women (average age ~30)
Risk factors: early sexual debut, multiple partners, cigarette smoking, immunosuppression
Often multicentric; 10–30% also have vaginal/cervical HPV lesions
Spontaneous regression of VIN possible, especially in younger women

2. HPV-Independent (~60–70%)

Arises from lichen sclerosus or lichen simplex chronicus
Precursor: differentiated VIN (dVIN)
Keratinizing SCC histology
Occurs in older women (average age ~75)
Driven by TP53 somatic mutations (also PIK3CA, NOTCH1, HRAS in some subtypes)
Higher risk of malignant progression, especially if age >45 or immunosuppressed

Clinical Features

Symptoms:

Vulvar pruritus (most common)
Vulvar mass, ulcer, or warty lesion
Vulvar bleeding or discharge
Enlarged inguinal lymph nodes (advanced disease)
Dysuria

Key points:

Physician delay in diagnosis is common (especially warty-appearing lesions mistaken for condylomata)
Any persistent, atypical vulvar lesion must be biopsied
Concurrent vaginal and cervical lesions must be excluded

Diagnosis

Biopsy is mandatory — Keys punch biopsy or wedge biopsy under local anesthesia
Must include sufficient underlying dermis to assess stromal invasion depth
Colposcopy of the cervix and vagina to exclude synchronous lesions
Imaging (CT/MRI) to assess nodal and distant spread in advanced disease

Routes of Spread

Direct extension — to vagina, urethra, clitoris, anus
Lymphatic embolization — to inguinal → femoral → pelvic (external iliac) nodes
Hematogenous — lungs, liver, bone (rare; usually late)

Lymphatic spread pattern:

Superficial inguinal nodes (between Camper's fascia and fascia lata) → deep femoral nodes (medial to femoral vessels) → Cloquet's/Rosenmüller's node → pelvic nodes
Bilateral drainage from clitoris, anterior labia minora, and perineum
Contralateral nodal metastasis without ipsilateral involvement is rare (0–0.4%) for lateral tumors ≤2 cm
Overall inguinofemoral nodal metastasis rate: ~32%
Pelvic nodal metastasis: ~12% of cases (rare without groin involvement)

FIGO Staging (2009)

Stage	Description
IA	Tumor confined to vulva/perineum, ≤2 cm, stromal invasion ≤1 mm, negative nodes
IB	Tumor confined to vulva/perineum, >2 cm OR stromal invasion >1 mm, negative nodes
II	Tumor of any size, adjacent spread to lower 1/3 urethra, lower 1/3 vagina, or anus; negative nodes
IIIA	Positive inguinofemoral nodes: (i) 1 node ≥5 mm or (ii) 1–2 nodes <5 mm
IIIB	(i) ≥2 nodes ≥5 mm or (ii) ≥3 nodes <5 mm
IIIC	Positive nodes with extracapsular spread
IVA	Invades upper 2/3 urethra, upper 2/3 vagina, bladder, rectal mucosa, or fixed/ulcerated nodes
IVB	Distant metastases including pelvic nodes

Treatment

Primary Tumor Management

Microinvasive (Stage IA — ≤2 cm, ≤1 mm invasion):

Wide local excision only; lymphadenectomy may be safely omitted

Early disease (T1b–early T2, unifocal):

Radical local excision (1–2 cm margins, down to deep perineal fascia) with ipsilateral or bilateral inguinofemoral lymphadenectomy
Vulvar conservation is preferred over radical vulvectomy for unifocal tumors

Sentinel lymph node (SLN) biopsy:

Suitable for unifocal tumors <4 cm with clinically negative nodes
Eliminates full inguinofemoral lymphadenectomy in node-negative patients
Must be performed in experienced centres

Advanced disease (large T2 / T3):

Chemoradiation followed by limited surgical resection (avoids exenteration)
Preoperative radiation to reduce tumor bulk and preserve sphincters/urethra

Groin Node Management

Full inguinofemoral lymphadenectomy when groin dissection is indicated
Separate groin incisions (rather than en bloc) improve wound healing
Contralateral groin dissection may be omitted for strictly lateral T1 tumors with negative ipsilateral nodes
Postoperative (chemo-)radiation to the groins for patients with multiple positive inguinofemoral nodes — decreases groin recurrence risk

Recurrent Disease

Groin recurrence is almost universally fatal
Local recurrence may be salvageable with re-excision ± radiation
Systemic chemotherapy (cisplatin-based) and immunotherapy (pembrolizumab for PD-L1 positive/MSI-H) for metastatic disease

Prognosis

The single most important prognostic factor is lymph node status:

Nodal Status	5-Year Survival
Negative groin nodes	>90%
Positive groin nodes	~50%
Groin recurrence	Nearly 0%

Other adverse prognostic factors: depth of invasion, tumor size, extracapsular nodal extension, and positive surgical margins.

Key Takeaway Points

(from Berek & Novak's Gynecology)

All vulvar lesions require biopsy to avoid diagnostic delay
Management is multidisciplinary and individualized
Primary lesion and groin node management are determined separately
Most T1/early T2 lesions → radical local excision
Large T2/T3 → chemoradiation, then limited resection
SLN dissection suitable for unifocal <4 cm, clinically node-negative tumors
If groin dissection needed → thorough inguinofemoral lymphadenectomy
Postoperative (chemo-)radiation for multiple positive groin nodes

Sources: Berek & Novak's Gynecology; Schwartz's Principles of Surgery, 11th ed.; Robbins, Cotran & Kumar Pathologic Basis of Disease; Sabiston Textbook of Surgery. A 2025 IJGO update on vulvar cancer also reports emerging targeted therapies with ~20% overall response rates in recurrent/metastatic vaginal/vulval cancers.

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