Risk factors for the development of vulvar cancer include increasing age, infection with human persistent papillomavirus (HPV), early age at first sexual intercourse, multiple sexual partners, sexually transmitted infections such as Herpes Simplex, smoking, inflammatory conditions of the vulva (i.e. lichen sclerosis, lichen planus), family history of vulvar cancer, personal history of cervical cancer, and low socioeconomic status prior pelvic radiation, and immunodeficiency immunosuppression (often associated with HIV) (7)

Premalignant lesions of the vulvar called vulvar intraepithelial lesions include Low-grade intraepithelial lesion (LSIL), High grade intraepithelial lesion (HGSIL) and the differentiated variant (dVIN). dVIN represents 5% of the pre-neoplastic lesions of the vulvar with worse prognosis, high recurrence and higher rate of progression to SCC.

Vulvar SCC represents 90% of all vulvar cancers and typically develops by one of two different pathways. Thirty to forty per cent of vulvar cancer cases are associated with high-risk human papillomavirus (HR-HPV). HPV is known to have E6 and E7 oncoproteins, which inactivate the p53 and RB tumour suppressor proteins, respectively resulting in unregulated hyperproliferation. Another pathway involves inflammatory changes that result in cells with intact p53 status but the loss of cyclin-dependent kinase inhibitor 2A which also results in unregulated cell cycle proliferation and eventually cancer(8)(9)  This represents the pathway for the dVIN variant arising from lesion such as Lichen sclerosus.  The histological types of vulvar cancer include Squamous cell carcinoma, Basal cell carcinoma, Paget’s disease of the vulva, Vulvar melanoma, Verrucous carcinoma, Sarcoma, Bartholin’s gland cancer and other adenocarcinomas.

VC can be asymptomatic or present with vulvar irritation, pruritus or pain. Most patients with vulvar melanoma present with advanced symptoms, including bleeding, mass, and ulceration (10)

Vulvar Paget disease can have a very nonspecific presentation, which often leads to a delay in diagnosis. Similarly, Bartholin’s gland carcinoma presents nonspecifically as a painless visible tumour and is often misdiagnosed and incorrectly treated as an abscess or cyst before a definitive diagnosis (11). Suspicion is raised when it occurs in women older than 40 years.

A physical exam may show a scaly patch, plaques, an erythematous lesion, or an ill-defined mass. Lesions of verrucous carcinoma typically have a cauliflower-like appearance. Any suspicious lesions require further investigation, including a thorough pelvic exam, and colposcopy of the vulva and vagina, and biopsy (12). In cases of vulvar melanoma, attention to the ABCDE rule (a dermatologic acronym for asymmetry, border irregularity, colour, diameter, and evolving) can aid in clinical diagnosis.

Cutaneous squamous cell carcinoma

Cutaneous basal cell carcinoma

Cutaneous melanoma

Atopic dermatitis

Psoriasis

Lichen sclerosis

Lichen planus

Lichen chronicus simplex

Contact dermatitis

Candidiasis

Pemphigus vegetans

Mycosis fungoides.

Complete blood count (establishes a baseline)

Electrolyte, urea and creatinine (establishes a baseline)

HIV testing (to detect immunosuppression)

Pap smear.

HPV testing.

Vulvar biopsy (to establish a definitive diagnosis)

Colposcopy

Imaging studies (magnetic resonance imaging, computed tomography and positron emission tomography-CT). (to detect metastatic spread of tumour)

Cystoscopy (to detect bladder involvement)

Proctoscopy (to detect rectal involvement)

Stage I: Tumors are confined to the vulva or perineum, with no nodal metastasis.

IA: Tumor ≤2 cm with stromal invasion ≤1 mm

IB: Tumor >2 cm or stromal invasion >1 mm

Stage II: Tumor of any size with extension to lower one-third of the urethra, lower one-third of the vagina, lower one-third of the anus with negative nodes

Stage III: Tumor of any size with extension to upper part of adjacent perineal structures, or with any number of nonfixed, nonulcerated lymph node

IIIA: Tumor of any size with disease extension to upper two-thirds of the urethra, upper two-thirds of the vagina, bladder mucosa, rectal mucosa, or regional lymph node metastases ≤5 mm

IIIB: Regional   lymph node metastases >5 mm

IIIC: Regional  lymph node metastases with extracapsular spread

Stage IV: Tumor of any size fixed to bone, or fixed, ulcerated lymph node metastases, or distant metastases

IVA: Tumour fixed to pelvic bone, or fixed or ulcerated regional   lymph node metastases

IVB: Any distant metastasis.

Surgical excision is the standard therapy for vulvar cancer, but adjuvant radiation and chemotherapy may be recommended depending on the histopathology and extent of the disease. Surgery is the primary treatment of early-stage disease. Sentinel lymph node mapping can be done to determine the need for lymphadenectomy. The aim of the procedure is to detect nodal metastases in the “sentinel” node (which primarily drains the tumor), and then to omit a full lymphadenectomy in sentinel node negative patients, thereby decreasing the morbidity associated with a complete inguinofemoral node dissection. When an ipsilateral sentinel lymph node is not detected, a complete ipsilateral inguinofemoral lymphadenectomy must be done. In addition, if an ipsilateral sentinel lymph node is positive, a complete bilateral inguinofemoral lymphadenectomy is recommended.

For SCC with a depth of invasion ≤1mm, wide-local excision without lymphadenectomy is sufficient with a recommended surgical margin of 1 to 2 cm. If tumour depth is greater than 1mm or tumour diameter exceeds 2 cm, radical resection with margins extending to the perineal fascia and inguinal lymph node assessment should be performed.

Radiation is recommended for vulvar cancer. indications for pelvic and groin irradiation

in patients with positive groin nodes are:

1. Presence of extracapsular spread.
2. Two or more positive groin nodes

Use of targeted therapy has been recognized in the management of vulvar cancer. Inhibition of EGFR has been successfully utilized and published for vulvar cancer. Erlotinib, an EGFR inhibitor, showed a clinical benefit rate of 67% in women with metastatic vulvar cancer.

Local recurrences most often occur in the first 2 years after treatment, and most women with gynecological malignancies are seen every 3–6 months for the first 2 years, and then every 6–12 months until they are 5 years post treatment. The surveillance visit should include a review of symptoms relevant to recurrence or adverse effects of treatment, and thorough clinical examination.

Prognostic factors include age, performance status (ECOG status), microscopic residual resection, tumour stage, grading and chemoradiation.

Patients should be encouraged to receive the HPV vaccine early in life to reduce their overall risk of contracting the HPV virus and thus reduce their risk of contracting HPV-dependent vulvar cancer.