HPV-related Vulvar Diseases and Perspectives of p16INK4aImmunochemistry: A Review of the Literature

Introduction Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4aimmunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap.Methods A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.govand Scopus. The key search terms were HPV, VIN, p16INK4aimmunochemistry and p53.Results We found that nuclear and cytoplasmic immunostaining for p16INK4awas intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease.Conclusions Our findings indicated that p16INK4aor p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.