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

Abstract

ObjectiveThis 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.MethodsAll 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.ResultsA 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).ConclusionThe p16INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.

Plasma endothelin-1-related peptides as the prognostic biomarkers for heart failure

“…Otherwise, the pooled RRs were estimated by the fixed-effect model. [ 23 ] The inconsistency index ( I 2 ) was calculated to assess the variation caused by heterogeneity. The value of I 2 between 0 and 25% represents insignificant heterogeneity, 26 and 50% as low heterogeneity, 51 and 75% as moderate heterogeneity, and more than 75% as high heterogeneity.…”

Overexpression of p16INK4a Serves as Prognostic Marker in Squamous Cell Vulvar Cancer Patients Treated With Radiotherapy Irrespective of HPV-Status

“…Only p16 INK4a -overexpression correlated with prolonged OS and predicted a better response to irradiation (15). Additionally, a large meta-analysis of 2,309 patients suggested that p16 INK4a -status itself is associated with a better prognosis in vulvar cancer patients and indicates higher radiosensitivity (14). There are current studies investigating other molecular mechanisms leading to higher radiosensitivity of p16 INK4a -positive VSCCs, suggesting that immunologic effects depending on p16 INK4a -overexpression contribute to better outcome (26).…”

“…Furthermore, overexpression of the cell cycle regulator protein p16 INK4a correlates with the presence of HPV DNA in cervical, anal or oropharyngeal cancer and p16 INK4a -overexpression has been found to be of independent prognostic value for the response to radiation treatment (6, 8–13). A recent study revealed substantial mismatch between p16 INK4a -overexpression and HPV DNA detection in VSCC and evidence arises that p16 INK4a itself might function as an independent prognostic marker in vulvar cancer patients irrespective of an association with HPV (14, 15).…”

Viral Oncology: Molecular Biology and Pathogenesis

“…Unlike cervical cancer, no routine screening is performed for vulvar or vaginal SCC [ 263 ]. Vulvar SCC that is associated with HPV infection has an earlier age of onset and is correlated with lesser stage and negative lymph node metastasis as compared to HPV-negative vulvar SCC [ 266 ].…”