Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

Cancer Medicine

Hisato Kawakami⁴  Isamu Okamoto⁴  Kyoichi Terao⁵  Kazuko Sakai¹  Minoru Suzuki²  Shinya Ueda⁴  Kaoru Tanaka⁴  Kiyoko Kuwata⁴  Yume Morita⁴  Koji Ono²  Kazuto Nishio¹  Yasumasa Nishimura³  Katsumi Doi⁵ 

[1] Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan;Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, Japan;Department of Radiation Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan;Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan;Department of Otolaryngology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan

关键词: DNA methylation;    human papillomavirus;    oropharynx;    p16;    squamous cell carcinoma;   

DOI  :  10.1002/cam4.151

来源: Wiley

【 摘 要 】

Abstract

Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074–0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.