Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis

Abstract

Objective The purpose of this study was to determine the association between active tobacco exposure and aberrant p16 promoter methylation in primary cervical squamous cell cancer and high-grade squamous cervical dysplasia. Study design p16 methylation–specific polymerase chain reaction was performed on DNA that was extracted from 60 cervical cancers, 30 high-grade dysplasia specimens, and 78 normal cervical cytologic specimens. Patient data were obtained by medical record review or were collected prospectively. Results Aberrant p16 methylation was significantly higher in squamous cell cervical cancers (61%) than in squamous high-grade dysplasia (20%) or normal cytologic specimens (7.5%). Approximately one half the women with squamous cancer and one half of the women with high-grade dysplasia were active smokers. Aberrant p16 methylation was associated with active tobacco use in patients with squamous carcinoma (odds ratio, 20.6; 95% CI, 3.6-118; P<.001) and high-grade dysplasia (odds ratio, 4.57; 95% CI, 1.63-12.78; P = .002). Conclusion Aberrant p16 methylation is associated strongly with active tobacco use in squamous cell cervical cancers and high-grade dysplasia.