Abstract: Vulvar carcinoma is a rare and aggressive gynecological malignancy. It affects elderly females, with the mean age at diagnosis being 55–60 years. Regional metastasis to inguinal lymph nodes is common. There is a high incidence of pelvic node involvement, especially in those with pathologically positive inguinal nodes. Surgery appears to be the only curative treatment option in the early stages of the disease. But in most patients, surgery is associated with considerable morbidities and psychosexual issues. Hence, in the quest for a less morbid form of treatment, multimodality approaches with various combinations of surgery, chemotherapy, and radiation therapy have been suggested for advanced vulvar cancers. Due to the low incidence of the disease, the level of evidence for the success of these treatment modalities is poor. In countries like India, a heterogeneous incidence of vulvar carcinoma exists across the country, with patients presenting at advanced stages when the option of surgery is often supplemented or replaced by chemotherapy and radiotherapy. In this review, we attempt to study the available published literature and trials and discuss the treatment options in various stages of vulvar carcinoma.
Keywords: vulva, vulvectomy, radiotherapy, WLE, chemoradiation, review, management
Worldwide, vulvar carcinoma is rare, constituting approximately 4% of all gynecological malignancies. However, the rates for new cases of vulvar cancer have been increasing by about 0.6% every year over the past 10 years. Death rates too have been rising, at the average rate of 1.2% each year between 2005 and 2014.1 About 43% of vulvar carcinomas are due to human papilloma virus (HPV). 2 HPV 16 and 33 are the predominant subtypes, accounting for 55.5% of all HPV-related vulvar cancers. More than 60% of all vulvar cancers occur in the more developed nations. Squamous cell carcinoma constitutes 70% of vulvar carcinomas. There are 2 distinct histological patterns of vulvar carcinomas, with 2 different risk factor profiles. 1) The basaloid/warty lesions are more common in young women, being commonly associated with HPV DNA (75%–100%). This subtype simulates the risk factor profile of cervical cancer. 2) The keratinizing vulvar carcinomas represent the majority of the vulvar lesions (>60%). They occur more often in older women and are rarely associated with HPV.3 The other different less common histologies are melanoma, basal cell, Bartholin gland adenocarcinoma, sarcoma, and Paget’s disease. The risk of developing vulvar carcinoma is related to different behavioral, reproductive, hormonal, and genetic aspects. Factors that increase the risk include other genital cancers, chronic inflammatory diseases of the vulva, smoking, history of genital warts, and vulvar intraepithelial neoplasia. Paget’s disease of the vulva is a rare disease, with incidence reports varying between <1% and 2% of vulvar malignancies.4 It is most common in postmenopausal Caucasian women. The underlying cause is not very well understood. In ~25% of women, Paget’s disease of the vulva is invasive and the prognosis in such cases is worse than in non-invasive cases. Unfortunately, recurrence rates are very high (33%), even in cases with clear margins, and still higher in cases with close or positive surgical margins, regardless of invasion. Traditionally, surgical excision with or without inguinofemoral lymph node dissection, has remained as the treatment of choice. Radiotherapy has been used as a primary treatment option for patients who were not eligible for surgery or who refused surgery and also a treatment option for patients with recurrence after surgery. Recent studies, however, show that imiquimod cream may be an effective and safe alternative.5
Cancer registry in India, as in 2015, showed a heterogeneous incidence of vulvar carcinoma across the country. During the year 2003–2007, the crude rate per 100,000 women per year in Delhi was found to be 0.3, while it was 0.4 in Bangalore, 0.5 in Mizoram and 0.2 using.6 A pooled incidence in different cities showed a rise in incidence between the age groups of 50 and 70 years. While both cervical and vulvar cancers are caused by HPV, research is required to understand why the former is more common than the latter.
Due to the rarity of the cancer and lack of randomized trials, management of this aggressive disease is shrouded with dilemmas and controversies. Although surgery has remained the cornerstone in the management of vulvar carcinoma, especially in the early stages, the morbidities associated cannot be overlooked. This has led to changing paradigms in the surgical management from the mutilating radical en bloc procedures to triple incision techniques to the present radical local excisions, mainly to maintain the sexual identity and satisfactory body image of the affected patient, and to decrease the surgery-associated morbidity.
In countries like India, where patients present at an advanced stage, the option of surgery is often replaced by chemotherapy and radiotherapy. In a recent study from India, 51.2% patients presented in stage III–IV when surgery was not a treatment option.7 Hence, this review article is being presented as an Indian perspective and it is our endeavor to bring out the dilemmas regarding the modes of management of vulvar carcinoma, with emphasis on the newer conservative forms of treatments.