Comprehensive Guide to Vulvar Cancer: Causes, Symptoms, Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Vulvar cancer accounts for approximately 5% of all gynaecological malignancies, with approximately 6,500 new cases diagnosed per year in the United States and an incidence that has been gradually rising over recent decades, partly attributed to increasing rates of HPV infection. Squamous cell carcinoma (SCC) comprises approximately 90% of all vulvar cancers. Two clinically and aetiologically distinct pathways to vulvar SCC are recognised, each affecting a different patient demographic. The HPV-related pathway — affecting younger women (median age approximately 50 years) — proceeds from high-risk HPV infection (predominantly HPV-16) through usual-type vulvar intraepithelial neoplasia (uVIN, formerly VIN 2/3) to warty or basaloid invasive SCC; these tumours are p16-positive and have a better prognosis. The non-HPV-related pathway — affecting older postmenopausal women (median age approximately 70 years) — arises from a background of chronic vulvar dystrophy, particularly lichen sclerosus, through differentiated VIN (dVIN) to keratinising SCC; these tumours are p16-negative, frequently harbour TP53 mutations, and are biologically more aggressive. Less common vulvar malignancies include melanoma (approximately 5%), Bartholin gland adenocarcinoma, Merkel cell carcinoma, extramammary Paget's disease (an intraepithelial adenocarcinoma), and rare sarcomas. The labia majora are the most commonly affected anatomical site, followed by the labia minora and clitoris.

Risk factors for vulvar SCC are determined by the underlying aetiological pathway. For HPV-related vulvar SCC, the primary risk factors are high-risk HPV infection — particularly HPV-16, present in approximately 40-60% of vulvar SCCs — and the associated risk factors that promote viral persistence and progression: multiple sexual partners, early sexual debut, history of other HPV-related lower genital tract malignancies (cervical, vaginal), cigarette smoking (which impairs local immune surveillance and promotes HPV persistence by approximately 3-5-fold), and immunosuppression from HIV/AIDS or solid organ transplantation (which dramatically elevates risk, with HIV-positive women having a 10-15-fold elevated vulvar cancer risk). For non-HPV-related vulvar SCC, the primary aetiological factor is lichen sclerosus — a chronic vulvar inflammatory dermatosis causing thinning, whitening, and architectural distortion of vulvar skin — which undergoes malignant transformation in approximately 3-5% of affected women over decades through the intermediate dVIN (differentiated VIN) stage; lichen planus is a less common but recognised precursor. Prior pelvic or vulvar radiotherapy (e.g., for cervical or rectal cancer) can cause radiation-induced vulvar SCC years to decades after treatment. Age is a non-modifiable risk factor for both pathways: risk increases progressively from the fifth decade onwards. First-degree family history of vulvar cancer is a minor risk factor, though no major hereditary syndrome specifically predisposes to vulvar SCC.

Vulvar cancer is characterised by a prolonged preinvasive phase that can produce symptoms for months to years before invasive carcinoma develops, providing opportunities for earlier detection if symptoms are promptly evaluated. The most common presenting symptoms are chronic vulvar pruritus (itching) and burning or pain, which are frequently attributed to more common benign conditions including candidal infection, contact dermatitis, or lichen sclerosus — with resulting delays in diagnosis of 6-24 months on average. A palpable vulvar lump, nodule, or mass is the most specific symptom prompting urgent medical evaluation. Ulceration, crusting, bleeding, or a non-healing sore on the vulva are alarm symptoms requiring biopsy. Skin colour changes — areas that appear white (leukoplakia), red (erythroplakia), or dark/melanotic — on the vulva that persist or enlarge despite treatment warrant histological assessment. Superficial spreading Paget's disease of the vulva presents as a slowly enlarging, eczematous, persistent red, sometimes crusted plaque with well-demarcated edges that is frequently misdiagnosed and mistreated as a dermatological condition for years. Inguinal lymphadenopathy — unilateral or bilateral — indicates regional nodal metastasis in clinically advanced disease. Vaginal discharge, dyspareunia, and dysuria are less common and suggest locally advanced disease with adjacent organ involvement. Significant diagnostic delay is a recognised problem in vulvar cancer: multiple studies report a median delay of 6 months or more from symptom onset to specialist assessment.

Any suspicious vulvar lesion — particularly a non-healing ulcer, raised nodule, or area of leukoplakia/erythroplakia persisting for more than 4 weeks — requires histological biopsy for definitive diagnosis. Punch biopsy or incisional biopsy under local anaesthesia is the standard procedure; excisional biopsy is appropriate for small lesions. Colposcopy with acetic acid application aids in identifying multifocal VIN. MRI of the pelvis with gadolinium contrast is the optimal imaging modality for assessing depth of invasion, involvement of the urethra, vagina, anus, or bony pelvis, and pelvic lymph node status. PET/CT with 18F-FDG provides sensitive evaluation of inguinal, pelvic, and distant lymph node involvement and is increasingly used in the staging of higher-stage tumours. The FIGO staging system (2021 revised) for vulvar cancer stages tumours from Stage I (confined to the vulva or perineum, negative nodes) through Stage IVB (distant metastases). Sentinel lymph node biopsy (SLNB) using 99m-technetium (radiocolloid) with or without patent blue dye or indocyanine green fluorescence is validated as a safe alternative to full inguinofemoral lymphadenectomy (IFLD) for T1b-T2 tumours with clinically negative inguinal nodes and a tumour diameter of less than 4 cm, based on the GROINSS-V trial; SLNB-negative patients are spared IFLD and its associated chronic lymphoedema. HPV/p16 testing and TP53 sequencing characterise the aetiological pathway and guide immunotherapy eligibility. MSI/dMMR testing may guide use of checkpoint inhibitors in advanced disease.

Surgical resection remains the cornerstone of curative treatment for locoregional vulvar cancer. Wide local excision (WLE) with a 1 cm clinically negative margin is the standard surgical procedure, replacing the historical radical vulvectomy for most cases. The goal is R0 resection (microscopically clear margins): positive margins are associated with a 2-3-fold increased local recurrence risk and necessitate re-excision or adjuvant radiotherapy. Radical vulvectomy — removing the entire vulva including the labia majora and minora, clitoris, and perineal body — is reserved for T3-T4 tumours with extensive local involvement. Sentinel lymph node biopsy (SLNB) is performed for eligible T1b-T2 tumours (primary tumour diameter less than 4 cm, no fixed/ulcerated inguinal nodes, lesion not involving the midline); SLNB-positive patients (any macrometastasis, micrometastasis, or isolated tumour cell) require completion inguinofemoral lymph node dissection or inguinal radiotherapy. Full bilateral inguinofemoral lymphadenectomy is performed for T3-T4 tumours, clinically suspicious lymph nodes, or intraoperative SLNB technical failure. Adjuvant concurrent chemoradiation (cisplatin weekly 40 mg/m² plus EBRT 45-54 Gy to the vulva, perineum, and inguinopelvic nodes) is recommended for: positive surgical margins not amenable to re-excision, two or more inguinal node micrometastases, one or more inguinal node macrometastases, extracapsular nodal extension, or pT3-T4 primary tumour. Neoadjuvant cisplatin-based chemoradiation is used to downstage initially unresectable T3-T4 tumours abutting the anus, urethra, or clitoris where upfront surgery would require exenterative procedures. Advanced/metastatic vulvar SCC: cemiplimab (anti-PD-1) for locally advanced or metastatic cutaneous SCC not amenable to surgery or radiation; platinum-based chemotherapy (carboplatin-paclitaxel) as first-line systemic therapy.

Prevention of vulvar cancer encompasses both primary prevention targeting HPV infection and secondary prevention through surveillance and treatment of pre-invasive lesions. HPV vaccination with Gardasil 9 — targeting nine HPV types including HPV 16 and 18, which account for approximately 80% of HPV-positive vulvar SCCs — is the most effective primary preventive measure for the HPV-related pathway of vulvar cancer. Vaccination is recommended at ages 9-26 years; catch-up vaccination for adults aged 27-45 years is recommended by ACIP on shared-decision making. Population-level HPV vaccination programmes have demonstrated reductions in VIN 2/3 incidence in vaccinated cohorts, consistent with preventing HPV-related vulvar cancer at the precursor stage. For the non-HPV pathway, management of lichen sclerosus is the primary preventive strategy: high-potency topical corticosteroids (clobetasol propionate 0.05% ointment) applied according to a structured maintenance regimen significantly suppress inflammation, reduce symptoms, reverse early skin changes, and reduce the risk of dVIN and invasive SCC development, though they do not eliminate it entirely. Women with lichen sclerosus require annual or biannual vulvoscopic examination with biopsy of any non-healing area, new growth, or change in appearance. Smoking cessation reduces HPV persistence and the risk of HPV-related vulvar cancer. Regular annual gynaecological examination including careful vulvar inspection enables detection of VIN and early invasive cancer before symptoms develop. Immunosuppressed women — particularly HIV-positive women and solid organ transplant recipients — require more frequent gynaecological surveillance, including vulvoscopy.

Any vulvar symptom that persists for more than 4 weeks without complete resolution after standard treatment for a presumed benign cause requires gynaecological evaluation with clinical examination, colposcopy if indicated, and biopsy of any suspicious area. Do not repeatedly treat presumed fungal vulvovaginitis or contact dermatitis without improvement without seeking specialist examination, as vulvar cancer is commonly misdiagnosed and mistreated for 6-24 months before the correct diagnosis is made. Specific symptoms requiring prompt specialist assessment include: a new vulvar lump or hardness; a non-healing ulcer or sore on the vulva or perineum; a white or red vulvar skin lesion that is enlarging; vulvar bleeding not associated with trauma or menstruation; and persistent vulvar pruritus that is inadequately controlled by standard treatments. Women with known lichen sclerosus should attend their regular surveillance appointments — typically annually — and must report any new lesion, growth, hardening, or non-healing area between appointments without delay, as these may indicate dVIN or early invasive cancer. Any inguinal lymph node enlargement in a woman — particularly if firm, hard, or progressively enlarging — requires clinical examination and imaging to exclude vulvar or other gynaecological malignancy. Women who have previously been treated for VIN, vulvar cancer, CIN, or cervical cancer require regular vulvoscopy as part of their surveillance programme and should not delay reporting recurrent vulvar symptoms.

Stage I: 5-year OS approximately 80-90%. Stage II: approximately 60-75%. Stage III (positive inguinal nodes): approximately 40-55%. Stage IVB (distant metastasis): less than 20%. Inguinal lymph node metastasis is the strongest prognostic factor. HPV-positive vulvar SCCs may have better response to chemoradiation. Sentinel node biopsy has reduced post-operative lymphoedema morbidity compared to full groin dissection for node-negative patients. The prognosis for Comprehensive Guide to Vulvar Cancer: Causes, Symptoms, Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.