Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis

OBJECTIVE This study aimed to examine the prognostic value of overexpressed p16INK4a in vulvar cancer. Although the tumor suppressor p16INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear. METHODS All publications in English language on the association between p16INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger's regression test. RESULTS A total of 17 studies with 2309 patients were included. The p16INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage (I+II vs III+IV; OR = 0.60, 95%CI: 0.41-0.86, P = 0.006), negative lymph node metastasis(negative vs positive; OR = 0.61, 95%CI: 0.39-0.95, P = 0.029), patient's age <55 (OR = 0.54, 95%CI: 0.31-0.96, P = 0.034), human papillomavirus-positive status (OR = 0.01, 95%CI: 0.00-0.11, P<0.001), and higher overall survival (RR = 0.53, 95%CI = 0.35-0.80, P = 0.003). CONCLUSION The p16INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.