Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer

Abstract

Objectives: The objectives were to determine the prevalence of human papillomavirus (HPV) in mobile tongue cancer (MTC) and evaluate associations and survival.

Materials and methods: Patients who underwent surgical resection as primary treatment for MTC (n = 127) were retrospectively evaluated. Formalin-fixed paraffin-embedded (FFPE) specimens were assessed for p16 and p53 by immunohistochemistry; for HPV DNA by nested multiplex polymerase chain reaction (PCR) using two pairs of consensus primers (MY09–MY11 and GP5+–GP6+); and for E6 and E7 oncogenes from 13 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 66, and 68) by real-time reverse transcription PCR (RT-PCR).

Results: There were 18 (14.2%) p16-positive, 45 (35.4%) p53-positive, 9 (7.1%) HPV DNA-positive, and 7 (5.5%) E6 and/or E7 mRNA-positive tumors, but the correlation of all pairs was poor. There was no demographic or histopathologic association with HPV status. Cause-specific survival was significantly better with p16-positive than with p16-negative tumors (p = .037).

Conclusions: The prevalence of HPV and p16 positivity was relatively low and p16 status was a poor surrogate marker for HPV status. The results showed the importance of p16 expression in prognosticating mobile tongue cancer.

Chinese abstract

目的：目的是确定人乳头状瘤病毒（HPV）在移动性舌癌（MTC）中的发生率, 并评估相关疾病和生存率。

材料与方法：回顾性检测了接受手术切除术作为MTC主要治疗方法（n = 127）的患者。通过免疫组化法检测福尔马林固定石蜡包埋（FFPE）标本的p16和p53；通过嵌套多重聚合酶链反应（PCR）使用两对共有引物（MY09-MY11和GP5 + -GP6 +）进行HPV DNA检测； 通过实时PCR检测13种高危HPV类型（16,18,31,33,35,39,45,52,56,58,59,66和68）的E6和E7致癌基因。

结果：p16阳性有18例（14.2％）；p53阳性45例（35.4％）；HPV DNA阳性9例（7.1％）；E6及/或E7DNA阳性7例（5.5％）。然而, 所有对的相关性不明显。人口统计学或组织病理学与 HPV状态之间没有关联。 p16阳性的原因特性存活率明显高于p16阴性肿瘤（p = 0.037）。

结论：HPV和p16阳性的患病率相对较低, p16状态不能作为HPV状态的替代标记。结果显示p16表达对于预后移动性舌癌起着重要作用。

Keywords:

• Human papillomavirus
• head and neck squamous cell carcinoma
• mobile tongue cancer
• p16 immunohistochemistry
• p53 immunohistochemistry
• oncogene

Acknowledgements

The authors thank Associate Prof. Dr. H. Eguchi for his continuous support.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by Saitama Medical University International Medical Center under Grant [Hidaka Project 27D102].