Introduction

Vulvar cancer is a rare malignancy that accounts for fewer than 5 percent of all malignant tumors of the female genital tract. In the United States, approximately 5,150 new cases and 1,080 deaths from vulvar cancer occurred in 2015 [1]. 2014 data indicates the incidence of vulvar cancer is increasing in United States and other developed countries [2]. Vulvar cancer most commonly affects women in the seventh and eight decades of life with a median age at diagnosis of 70 years. Interestingly, it also appears that the age of diagnosis is decreasing. Messing and Gallup demonstrated that the average presenting age decreased from 69 to 55 years between 1979 and 1993 [3]. Others have corroborated this increasing burden of disease in younger patients [4].

Risk factors for vulvar cancer include tobacco use, multiple sexual partners, immunosuppression, human papilloma virus (HPV) infection, history of cervical cancer, and chronic vulvar dystrophies such as lichen sclerosis. In contrast to cervical cancer where 99.9 percent of cases are caused by HPV infection, only 40–60 percent of vulvar cancer cases are related to HPV. Most vulvar cancers are squamous cell carcinoma. Molecular and histopathologic studies have now demonstrated that vulvar squamous cell carcinoma develops in two distinct pathways, HPV independent and HPV dependent, based on etiologic and histologic characteristics [5–8].

In the past, vulvar cancer was usually treated with radical surgical excision and full inguinofemoral lymphadenectomy. Surgical techniques have been modified to decrease morbidity including modification of the extent of excision and the use of sentinel lymph node biopsy to evaluate lymph node metastasis. More recently, the use of neoadjuvant radiotherapy and/or chemotherapy has been demonstrated to effectively treat vulvar cancer patients who are not surgical candidates. Frequently, vulvar cancers are now treated with multimodal therapy including surgery, radiation and chemotherapy. In this chapter, topics pertinent to the understanding of the biology and management of vulvar malignancies are discussed.

Scope of the Problem

Epidemiology of HPV Independent Vulvar Cancers

HPV independent cancers commonly occur in elderly women. They are associated with chronic inflammation and vulvar dystrophies such as lichen sclerosis, lichen planus, lichen simplex chronicus, squamous cell hyperplasia, and vulvar intra-epithelial neoplasia II/III (differentiated types) [9–11]. This pathway usually leads to differentiated keratinizing squamous cell carcinoma [11].