Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas

Cancer. 2016 Jul 1;122(13):2021-30. doi: 10.1002/cncr.30021. Epub 2016 Apr 25.


Background: Patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs) have superior outcomes in comparison with patients with non-HPV-induced OPCs. This study confirms that a previously proposed HPV risk-adapted restaging system better reflects disease outcomes.

Methods: The National Cancer Data Base was used to analyze 8803 HPV+ OPC patients. Univariate and multivariate analyses were performed to identify the utility of both American Joint Commission on Cancer (AJCC) staging and HPV risk-adapted staging in predicting the outcomes of patients with HPV+ OPC and other factors influencing survival.

Results: With a median follow-up of 27.1 months, 3.2% had AJCC stage I disease and 6.6%, 19.4%, and 70.9% had stage II, III, and IV disease, respectively. When the patients were restaged according to HPV risk-adapted staging, 76.6% had stage I disease, 9.9% had stage II disease, and 13.5% had stage III disease. The 4-year overall survival rates according to HPV risk-adapted staging were 85.8%, 77.3%, and 64.6% for stages I, II, and III, respectively, but the rates for AJCC stages I, II, III, and IV were 90.1%, 86.1%, 87.0%, and 80.1%, respectively. Patients with HPV+ metastatic disease at diagnosis had a significantly improved median survival of 20.5 months versus 11.1 months with HPV- disease (P < .01). In the multivariate analysis, survival was also affected by the age at treatment, a nontonsillar or base-of-tongue primary site, private insurance, an annual income ≥ $48,000/y, and the comorbidity index (all P values < .01).

Conclusions: Outcomes of HPV+ OPC are significantly improved in comparison with HPV- OPC outcomes, and the current AJCC staging system does not accurately reflect disease outcomes. This study has retrospectively confirmed that an HPV risk-adapted restaging structure more accurately stratifies patients. Under this new risk-stratified staging system, patients may be more accurately stratified for investigation into treatment escalation or de-escalation studies. Cancer 2016;122:2021-30. © 2016 American Cancer Society.

Keywords: American Joint Commission on Cancer (AJCC); base of tongue; cancer; human papillomavirus (HPV); oropharyngeal cancer (OPC); oropharynx; stage; tonsil.

MeSH terms

  • Aged
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging / methods*
  • Oropharyngeal Neoplasms / pathology*
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / pathology
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Socioeconomic Factors
  • Survival Analysis
  • Survival Rate