Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

Giovanna Giordano, Cinzia Azzoni, Tiziana D'Adda, Alba Rocco, Letizia Gnetti, Elisabetta Froio, Carla Merisio, Mauro Melpignano

Research output: Contribution to journalArticlepeer-review


This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16INK4a, and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalPathology Research and Practice
Issue number3
Publication statusPublished - Mar 14 2008


  • Epithelial ovarian neoplasms
  • Human papilloma virus (HPV)
  • p16 and p53 immunoreactivity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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