Poor prognostic factors in human papillomavirus-positive head and neck cancer: who might not be candidates for de-escalation treatment?

Korean J Intern Med. 2019 Nov;34(6):1313-1323. doi: 10.3904/kjim.2017.397. Epub 2018 Nov 16.

Abstract

Background/aims: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC.

Methods: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed.

Results: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001).

Conclusion: Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

Keywords: De-escalation; Head and neck neoplasms; Human papillomavirus; Overall survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Decision-Making
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / virology
  • Host-Pathogen Interactions
  • Human Papillomavirus DNA Tests
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck / chemistry
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Time Factors

Substances

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