Research ArticlesEGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell CarcinomaZhang, Wei MD*,†; Jiang, Yinghao MSc*; Yu, Qingmiao MSc‡; Qiang, Shaoying MSc§; Liang, Ping MSc*; Gao, Yane MD‡; Zhao, Xingye BSc*; Liu, Wenchao MD§; Zhang, Ju PhD*Author Information *Institute of Gene Diagnosis, State Key Laboratory of Cancer Biology, School of Pharmacology Departments of †Gynecology and Obstetrics §Oncology, Xijing Hospital, The Fourth Military Medical University ‡Department of Gynecology and Obstetrics, 2nd Affiliated Hospital, Medical School of Xian Jiaotong University, Xian, Shaanxi, China W.Z., Y.J., W.L., and J.Z. are the first co-authors. W.Z. and Y.J. contributed equally. Supported by the National High-tech R&D Program (2008AA02Z444) and the National Nature Science Foundation (81071435, 81371891). The authors declare no conflict of interest. Reprints: Ju Zhang, PhD, Institute of Gene Diagnosis, State Key Laboratory of Cancer Biology, School of Pharmacology, The Fourth Military Medical University, Xian, Shaanxi 710032, China (e-mail: [email protected]). Received March 2, 2014 Accepted July 12, 2014 Applied Immunohistochemistry & Molecular Morphology: October 2015 - Volume 23 - Issue 9 - p 661-666 doi: 10.1097/PAI.0000000000000128 Buy Metrics Abstract Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor–sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor–sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P<0.01). This study suggested that there was no EGFR tyrosine kinase inhibitor–sensitive mutation in EGFR exons 18, 19, and 21 in Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation was common and it might be associated with HPV 16 infection in Chinese cervical squamous cell carcinoma. The results provided a novel understanding and an applicable pharmacogenomic tool for individualized management of cervical cancer patients. Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.