Open AccessHuman papillomavirus DNA and p16 expression in J apanese patients with oropharyngeal squamous cell carcinoma
Author(s) -
Kawakami Hisato,
Okamoto Isamu,
Terao Kyoichi,
Sakai Kazuko,
Suzuki Minoru,
Ueda Shinya,
Tanaka Kaoru,
Kuwata Kiyoko,
Morita Yume,
Ono Koji,
Nishio Kazuto,
Nishimura Yasumasa,
Doi Katsumi,
Nakagawa Kazuhiko
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.151
Subject(s) - dna methylation , cancer research , oncology , hazard ratio , polymerase chain reaction , dna , biology , carcinoma , gene , medicine , confidence interval , gene expression , genetics
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.