Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma

  • Toshiya MaebayashiEmail author
  • Naoya Ishibashi
  • Takuya Aizawa
  • Masakuni Sakaguchi
  • Tsutomu Saito
  • Jiro Kawamori
  • Yoshiaki Tanaka
  • Yukari Hirotani
  • Taku Homma
Head & Neck



Treatment guidelines have not been established for unknown primary head and neck squamous cell carcinoma (SCC). For these patients, chemoradiotherapy (CRT) can provide a better prognosis than that for patients with other head and neck cancers. The presence of HPV in the tumor is associated with a better outcome. However, not all patients with HPV-positive unknown primary head and neck SCC experience good treatment outcomes in actual clinical settings.


We thus retrospectively determined the Ki-67 proliferation index and p16 expression status to assess the associations of these parameters with treatment outcomes of patients with unknown primary head and neck SCC.


The subjects were 13 patients who underwent CRT after surgery or excision biopsy between 1999 and 2016. The 2- and 5-year overall survival (OS) rate was 76.9% and 68.4%, respectively. The prognostic factor was age. There was no significant difference in survival between patients with a high Ki-67 vs. low Ki-67 or between patients with p16-positive vs. p16-negative metastases OS. However, all p16-positive patients with low Ki-67 showed good locoregional control.


The combination of ki67 expression and p16 expression status may allow prediction of local control more accurately than p16 expression status alone.


Unknown primary head and neck squamous cell carcinoma Chemoradiotherapy Ipsilateral oropharynx and neck irradiation p16 Ki-67 



The authors thank Bierta Barfod for her contribution to the language editing of this manuscript.


No specific funding was received for this research.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

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.

Ethical approval retrospective studies

This study was approved by the institutional review board, and patient informed consent was obtained. (Trial registration number: Nihon University Itabashi Hospital Clinical Research Center RK-170214-9).

Informed consent

Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article. Documentation of informed consent for treatment was signed by each patient and placed in the patient’s medical record.

Research data policy

The dataset supporting the conclusions of this article is included within the article.

Consent for publication

copy of the written consent is available for review by the Editor-in-Chief of this journal.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RadiologyNihon University School of MedicineTokyoJapan
  2. 2.Radiology ClinicSonoda Medical HospitalTokyoJapan
  3. 3.Department of Radiation OncologySt. Luke’s International HospitalTokyoJapan
  4. 4.Department of Radiation OncologyKawasaki Saiwai HospitalKawasakiJapan
  5. 5.Department of Human Pathology, Division of Pathology and MicrobiologyNihon University School of MedicineTokyoJapan

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