HPV-related vulvar diseases and perspectives of p16INK4a immunochemistry: a review of the literature



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 p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap.


A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53.


We found that nuclear and cytoplasmic immunostaining for p16INK4a was 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.


Our findings indicated that p16INK4a or 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.

Tumori 2017; 103(6): 511 - 515

Article Type: REVIEW



Angela Carrone, Lucia Riganelli, Delia Savone, Assunta Casorelli, Lucia Merlino, Francesco Pecorini, Irene Pecorella, Pasquale Mancino, Maria Grazia Piccioni, Pierluigi Benedetti Panici

Article History


Financial support: None.
Conflict of interest: The authors declare they have no competing interests related to this article.

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  •  Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua - Italy
  •  Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University and Umberto I Polyclinic of Rome, Rome - Italy
  •  Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University and Umberto I Polyclinic of Rome, Rome - Italy

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