Research Papers:

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

Christian Grønhøj Larsen, David H. Jensen, Amanda-Louise Fenger Carlander, Katalin Kiss, Luise Andersen, Caroline Holkmann Olsen, Elo Andersen, Emilie Garnæs, Finn Cilius, Lena Specht and Christian von Buchwald _

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Oncotarget. 2016; 7:71761-71772. https://doi.org/10.18632/oncotarget.12335

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Christian Grønhøj Larsen1, David H. Jensen1, Amanda-Louise Fenger Carlander1, Katalin Kiss2, Luise Andersen2, Caroline Holkmann Olsen6, Elo Andersen3, Emilie Garnæs1, Finn Cilius4, Lena Specht5, Christian von Buchwald1

1Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

2Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

3Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

4Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

5Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

6Department of Pathology, Roskilde Hospital, Roskilde, Denmark

Correspondence to:

Christian von Buchwald, email: [email protected]

Keywords: oropharyngeal cancer, human papillomavirus, survival, nomogram

Received: August 04, 2016     Accepted: September 12, 2016     Published: September 29, 2016


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.

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PII: 12335