title: Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma.
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.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Terao
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kuwata
authors.forename: Yume
authors.initials: Y
authors.lastname: Morita
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000821:virology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D019175:DNA Methylation; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000821:virology*; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy / Q000821:virology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin
keywords: DNA methylation; human papillomavirus; oropharynx; p16; squamous cell carcinoma