Data from <i>p53 Arg72Pro</i> Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis

Abstract

<div>Abstract<p>Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the <i>Arg</i> allele of <i>p53 Arg72Pro</i> polymorphism binds more ardently with HPV E6 than the <i>Pro</i> variant. Here we evaluate the role of p53 <i>Arg72Pro</i> polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 <i>Arg</i> allele [OR 1.37; 95% confidence intervals (CI), 1.15–1.62; <i>P</i> < 0.001]. This association was not seen in HPV-negative individuals. <i>p53 Arg72Pro</i> was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The <i>Arg</i> variant of <i>p53 Arg72Pro</i> is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPV-negative patients. <i>Clin Cancer Res; 18(23); 6407–15. ©2012 AACR</i>.</p></div>