Molecular and serologic markers of HPV 16 infection are associated with local recurrence in patients with oral cavity squamous cell carcinoma
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Chung-Guei Huang1,2,3,*, Li-Ang Lee4,5,*, Chun-Ta Liao4,5, Tzu-Chen Yen4,6, Shu-Li Yang1,2, Yi-Chun Liu1, Jung-Chin Li4, Yu-Nong Gong1, Chung-Jan Kang4,5, Shiang-Fu Huang4,5, Ku-Hao Fang4,5, Kai-Ping Chang4,5, Li-Yu Lee4,7, Chuen Hsueh4,7, Shin-Ru Shih1,2,3, Kuo-Chien Tsao1,2
1Department of Laboratory Medicine, Head and Neck Oncology Group, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
2Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, ROC
3Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC
4Faculty of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
5Department of Otorhinolaryngology - Head and Neck Surgery, Head and Neck Oncology Group, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
6Molecular Imaging Center, Head and Neck Oncology Group, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
7Department of Pathology, Head and Neck Oncology Group, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
*These authors contributed equally to this work
Kuo-Chien Tsao, email: firstname.lastname@example.org
Keywords: oral cavity squamous cell carcinoma, human papillomavirus, mRNA expression, serology, local recurrence
Received: October 05, 2016 Accepted: March 20, 2017 Published: March 31, 2017
Human papillomavirus (HPV) infections predict mortality in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC). To address their prognostic significance for local recurrence (LR), in this retrospective cohort study we investigated different serologic and molecular markers of HPV 16 infection in 85 consecutive patients with primary OCSCC who received standard treatment and had their sera stored before treatment. Resected tumor specimens were examined with PCR-based assays for HPV 16 E6/E7 mRNA expression. Sera were tested with suspension arrays for the presence of HPV-specific antibodies using synthetic L1 and E6 peptides as well as a synthetic E7 protein. HPV 16 E6/E7 mRNA, anti-L1, anti-E6, and anti-E7 antibodies tested positive in 12%, 25%, 38%, and 41% of the study patients, respectively. Multivariate analysis identified pathological T3/T4, E6/E7 mRNA, and anti-E7 antibodies as independent risk factors for LR, whereas anti-E6 antibodies were an independent protective factor. In patients with ≥ 3 (high-risk group), 2 (intermediate-risk), and ≤ 1 (low-risk) independent risk factors (predictors), the 5-year LR rates were 75%, 42%, and 4%, respectively. Results were validated in an independent cohort. Together, our preliminary data indicate that HPV 16 infections as well as low and high serum levels of anti-E6 and anti-E7 antibodies, respectively, can serve as biomarkers of LR in patients with OCSCC, whereas the clinical usefulness of anti-HPV 16 antibodies for risk stratification of newly diagnosed cases deserves further scrutiny.
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