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

Hisato Kawakami, Isamu Okamoto, Kyoichi Terao, Kazuko Sakai, Minoru Suzuki, Shinya Ueda, Kaoru Tanaka, Kiyoko Kuwata, Yume Morita, Koji Ono, Kazuto Nishio, Yasumasa Nishimura, Katsumi Doi, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalCancer Medicine
Volume2
Issue number6
DOIs
Publication statusPublished - Jan 1 2013

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Squamous Cell Carcinoma
DNA
p16 Genes
Methylation
Cisplatin
Survival
Neoplasms
Multivariate Analysis
Cell Line
Polymerase Chain Reaction
Palatine Tonsil
Radiation Tolerance
DNA Methylation
DNA-Directed DNA Polymerase
Paraffin
Formaldehyde
Japan
Biomarkers
Lymph Nodes
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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

In: Cancer Medicine, Vol. 2, No. 6, 01.01.2013, p. 933-941.

Research output: Contribution to journalArticle

Kawakami, H, Okamoto, I, Terao, K, Sakai, K, Suzuki, M, Ueda, S, Tanaka, K, Kuwata, K, Morita, Y, Ono, K, Nishio, K, Nishimura, Y, Doi, K & Nakagawa, K 2013, 'Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma', Cancer Medicine, vol. 2, no. 6, pp. 933-941. https://doi.org/10.1002/cam4.151
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. / Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma. In: Cancer Medicine. 2013 ; Vol. 2, No. 6. pp. 933-941.
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AU - Suzuki, Minoru

AU - Ueda, Shinya

AU - Tanaka, Kaoru

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AU - Morita, Yume

AU - Ono, Koji

AU - Nishio, Kazuto

AU - Nishimura, Yasumasa

AU - Doi, Katsumi

AU - Nakagawa, Kazuhiko

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