Universität zu Köln

Rasmussen, J. H., Gronhoj, C., Hakansson, K., Friborg, J., Andersen, E., Lelkaitis, G., Klussmann, J. P., Wittekindt, C., Wagner, S., Vogelius, I. R. and von Buchwald, C. (2019). Risk profiling based on p16 and HPV DNA more accurately predicts location of disease relapse in patients with oropharyngeal squamous cell carcinoma. Ann. Oncol., 30 (4). S. 629 - 637. OXFORD: OXFORD UNIV PRESS. ISSN 1569-8041

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Abstract

Background: In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. Patients and methods: Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. Results: Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P = 0.006 (P = 0.013 in the validation cohort). Conclusion: Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rasmussen, J. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gronhoj, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hakansson, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Friborg, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andersen, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lelkaitis, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, J. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittekindt, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogelius, I. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Buchwald, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-151202
DOI:	10.1093/annonc/mdz010
Journal or Publication Title:	Ann. Oncol.
Volume:	30
Number:	4
Page Range:	S. 629 - 637
Date:	2019
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1569-8041
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN-PAPILLOMAVIRUS; NECK CANCERS; HEAD; PROGNOSIS; SURVIVAL; BIOMARKER; TIME Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15120