Vulval squamous cell carcinoma: a review.

Vulval squamous cell carcinoma (VSCC) represents approximately 90% of all vulval cancers. Despite its rarity relative to other gynaecological or skin malignancies, the recent growing body of epidemiological and clinical evidence has resulted in important refinements to national guidelines. This review offers a comprehensive overview of the current evidence regarding the epidemiology, clinical features, diagnosis, and management of VSCC. There are two distinct aetiological pathways currently identified in the pathogenesis of VSCC. Human papillomavirus (HPV)-dependent VSCC is commonly found in younger people, driven by a persistent infection of high-risk HPV genotypes (most commonly HPV16). HPV-independent VSCC arises in association with chronic inflammatory dermatoses (typically lichen sclerosus) owing to mounting DNA damage by oxidative stress and lipid peroxidation. Globally, the incidence of vulval cancer has been rising. In 2020, the Global Cancer Observatory reported the highest incidence rates in Western Europe, Northern America and Northern Europe. Although VSCC commonly presents with a 'suspicious vulval lesion', early symptoms may be wide-ranging and nonspecific, leading to diagnostic delays. This is further compounded by the stigma and embarrassment felt when discussing vulval symptoms. Diagnostic workup involves a clinical history and examination, vulvoscopy and multiple biopsies. The mainstay of treatment involves surgical excision with or without chemoradiotherapy, immunotherapy and lymph node biopsies, dependent on the Federation of Gynaecology and Obstetrics staging and progression. The prognosis is heavily dependent on stage. In England, 5-year crude net survival of early-stage VSCC (stage 1-2) is 78.2%, but it falls to 33.1% at later stages (stage 3-4). This is significantly poorer than cutaneous squamous cell carcinomas elsewhere. The advent of the HPV vaccine may be the first significant medical intervention to have an impact on VSCC incidence in decades.