Management of Early-Stage Vulvar Cancer

Abstract

Vulvar cancer is a rare gynecological malignancy since it represents 4% of all cancers of the female genital tract. The most common histological type is squamous cell carcinoma (90%). This type can be classified into two clinicopathological subtypes according to the etiology. The first subtype is associated with persistent human papillomavirus infection and is usually diagnosed in younger women. The second subtype is associated with lichen sclerosus condition, and in most cases is diagnosed in postmenopausal women. Currently, an increase in first subtype cases has been observed, which raised the concern about associated mortality and treatment morbidity among young women. Vulvar cancer treatment depends on histopathology grade and staging, but surgery with or without radiotherapy as adjuvant treatment is considered the gold standard. In recent decades, sentinel lymph node biopsy has been incorporated as part of the treatment. Therefore, we sought to review and discuss the advances documented in the literature about vulvar cancer focusing on the treatment of early-stage disease. Relevant articles, such as the GROINS-V studies and the GOG protocols, are presented in this review. Additionally, we discuss key points such as the evolution of treatment from invasive surgery with high morbidity, to more conservative approaches without compromising oncologic safety; the role of sentinel lymph node mapping in the initial staging, since it reduces the complications caused by inguinofemoral lymphadenectomy; the recurrences rates, since local recurrence is common and curable, however, groin-associated, or distant recurrences have a poor prognosis; and, finally, the long-term follow-up that is essential for all patients.

Keywords: diagnosis and staging; sentinel lymph node; vulvar cancer; vulvar neoplasms.

Figure 1

Vulvar anatomy.

Figure 2

Lymphatic drainage on the vulva. The blue and red colors are the circulatory system, in which the blue color is the venous system and the red color is the arterial system. The green color is the lymphatic system. The numbers (1 to 3) indicate the inguinal lymph nodes of the vulvar lymphatic drainage. Number 1 is the superficial inguinal lymph nodes, number 2 is the deep inguinal lymph nodes, and number 3 is the iliac lymph nodes.

Figure 3

Development of squamous cell carcinoma of the vulva. (A) Progression of usual type vulvar intraepithelial neoplasia (uVIN). Usual VIN: associated with HPV infection, the E6 oncoprotein of the virus degrades the tumor suppressor protein, p53, and the E7 oncoprotein inactivates the retinoblastoma protein, Rb, which is also a tumor suppressor protein, releasing transmission factors, E2F, causing cellular hyperproliferation. In immunohistochemistry, the p16 biomarker is positive and p53 is negative. (B) Progression of differentiated vulvar intraepithelial neoplasia (dVIN). Differentiated VIN: it is not related to HPV infection, but arises through chronic dermatoses, mainly lichen sclerosus and lichen planus, which can progress to squamous cell carcinoma of the vulva. In immunohistochemistry, the p16 biomarker is negative and p53 is positive. uVIN: usual type vulvar intraepithelial neoplasia; dVIN: differentiated vulvar intraepithelial neoplasia; HPV: human papillomavirus; IHC: immunohistochemistry; VIN: vulvar intraepithelial neoplasia.

Figure 4

Flowchart of the evaluation of the lymph nodes about the location of the tumor about the midline.

Figure 5

Flowchart of the treatment of metastatic lymph nodes.