Novel nomograms for survival and progression in HPV+ and HPV- oropharyngeal cancer: a population-based study of 1,542 consecutive patients

// Christian Gronhoj Larsen 1 , David H. Jensen 1 , Amanda-Louise Fenger Carlander 1 , Katalin Kiss 2 , Luise Andersen 2 , Caroline Holkmann Olsen 6 , Elo Andersen 3 , Emilie Garnaes 1 , Finn Cilius 4 , Lena Specht 5 , Christian von Buchwald 1 1 Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2 Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 3 Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark 4 Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 5 Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 6 Department of Pathology, Roskilde Hospital, Roskilde, Denmark Correspondence to: Christian von Buchwald, email: christian.von.buchwald@regionh.dk Keywords: oropharyngeal cancer, human papillomavirus, survival, nomogram Received: August 04, 2016      Accepted: September 12, 2016      Published: September 29, 2016 ABSTRACT Background: No study has combined tumour and clinical covariates for survival to construct an individual risk-profile for overall survival (OS), time to progression (TTP), and survival after progression (SAP) in patients with HPV+ and HPV– oropharyngeal squamous cell carcinoma (OPSCC). Based on the largest-to-date, unselected, population-based cohort of patients diagnosed with OPSCC, we performed a comprehensive analysis of long-term OS, TTP, and SAP and constructed novel nomograms to evaluate patients' prognoses. Results: At a median follow-up of 4.0 years (range: 0.8–15.8 yrs.), 690 deaths were recorded. The 5-year OS, TTP, and SAP for the HPV+/p16+ subgroup were 77%, 82%, and 33, vs. 30%, 66%, and 6% for the HPV–/p16– group ( P < 0.01). 376 patients failed to maintain disease control with a median TTP of 13 months in the HPV+/p16+ subgroup vs. 8.5 months in the HPV–/p16– subgroup ( P < 0.05). HPV combined with p16 status remained one of the most informative covariates in the final Cox regression model for OS, TTP, and SAP. Methods: We included all patients diagnosed with OPSCC ( n = 1,542) between 2000–2014 in Eastern Denmark. Survival rates were estimated by the Kaplan-Meier method. A multivariate Cox regression model was used to construct predictive, internally validated nomograms. Conclusion: The HPV+/p16+ subgroup had improved OS, TTP, and SAP compared with other combinations of HPV and p16 after adjusting for covariates. Nomograms were constructed for 1-, 5- and 10-year survival probability. Models may aid patients and clinicians in their clinical decision making as well as in counselling, research, and trial design.