Predictors of survival and recurrence after primary surgery for cervical metastasis of unknown primary

J Cancer Res Clin Oncol. 2020 Apr;146(4):925-933. doi: 10.1007/s00432-019-03111-x. Epub 2019 Dec 19.


Purpose: Cervical metastasis from unknown primary (CUP) is commonly classified as an advanced overall stage. P16 or human papillomavirus (HPV) positivity in metastatic lymph nodes (LN) might be associated with a favorable survival outcome of CUP. Therefore, we evaluated the prognostic values of p16 immuno-positivity in LN and other clinicopathological factors in patients with squamous cell carcinoma CUP (SCCUP).

Methods: This study involved 83 patients who underwent therapeutic neck dissection and panendoscopic examination and biopsy for suspected CUP. P16 immunostaining and HPV typing in LN were performed in 56 patients. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS).

Results: Postoperatively, primary tumors (PT) were found in 32 (38.6%) patients, mainly (90.6%) in the oropharynx, and not found in 51 (61.4%) patients. The clinicopathological data (except for histological grade) and 5-year OS and DFS rates did not significantly differ between patients with and without PT identification (all P > 0.05). P16 positivity was associated with favorable OS and DFS outcomes in the patients with PT (P < 0.05) but not in those without PT (P > 0.1). Multivariate analyses showed that age (> 60 years) and LN ratio (≥ 0.1) were the independent predictors of OS and DFS outcomes (all P < 0.05). P16 positivity or other factors were not independent factors.

Conclusion: Age and LN ratio are significant risk factors of survival and recurrence after primary surgery for SCCUP. Prognostic significance of LN p16 positivity should be further studied.

Keywords: Cervical metastasis of unknown primary; Recurrence; Risk factors; Survival; p16.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / secondary*
  • Head and Neck Neoplasms / surgery*
  • Head and Neck Neoplasms / virology
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neck Dissection
  • Neoplasm Recurrence, Local
  • Neoplasms, Unknown Primary / metabolism
  • Neoplasms, Unknown Primary / pathology*
  • Neoplasms, Unknown Primary / virology*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Prognosis
  • Retrospective Studies


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16