Patterns of disease events and causes of death in patients with HPV-positive versus HPV-negative oropharyngeal carcinoma

Radiother Oncol. 2022 Mar:168:40-45. doi: 10.1016/j.radonc.2022.01.021. Epub 2022 Jan 29.


Background and purpose: There have been no studies to date of patterns of events after oropharyngeal squamous cell carcinoma (OPC) treatment comprising disease progression immediately after treatment or after a disease-free interval (DFI), and causes of death, according to HPV status.

Materials and methods: Patients with a T1-4, N0-3, M0 OPC who completed treatment in a curative intent at our center between 2011 and 2020 were analyzed. A DFI was defined as the absence of the disease confirmed by both physical and radiological evaluation.

Results: We analyzed 888 patients, of who 451 were p16-positive and 437 were p16-negative. The 5-year survival rates were 82.4% vs. 44%, respectively (p < 0.0001, HR 0.24). The rates of disease progression at the end of the treatment without a DFI were 7.8% vs. 21.1% in the p16-positive vs. the p16-negative patients (p < 0.0001, OR 0.38). The 5-year competing risks of disease recurrence after a DFI were 5.6% vs. 20.5%, respectively (p < 0.0001, HR 0.26). Patients who were p16-positive had a lower risk of death from OPC disease (p < 0.0001, HR 0.23). The 5-year competing risks of a second primary cancer during follow-up were 16.1% vs. 49.9% (p = 0.0002) in the p16-positive vs. the p16- negative patients. Patients who were p16-positive had a lower risk of death from intercurrent causes (p < 0.0001, HR 0.17).

Conclusion: Clinical trials and medical interventions dedicated to each category of events and causes of death are needed to improve survival in HPV-positive and HPV-negative OPC patients.

Keywords: Death; Oropharyngeal neoplasms; Papillomavirus infections; Recurrence; Survival.

MeSH terms

  • Cause of Death
  • Cyclin-Dependent Kinase Inhibitor p16
  • Head and Neck Neoplasms*
  • Humans
  • Neoplasm Recurrence, Local
  • Oropharyngeal Neoplasms* / pathology
  • Papillomaviridae
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / pathology
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / therapy


  • Cyclin-Dependent Kinase Inhibitor p16