Associations Among Human Papillomavirus, Inflammation, and Fatigue in Patients With Head and Neck Cancer

• Authors: Canhua Xiao, Emory University; Jonathan Beitler, Emory University; Kristin Higgins, Emory University; Toby Glazer, Emory University; Linh Kha Huynh, Emory University; Sudeshna Paul, Emory University; Jennifer Felger, Emory University; Evanthia C. Wommack, Emory University; Nabil Saba, Emory University; Dong Shin, Emory University; Deborah Bruner, Emory University; Andrew Miller, Emory University
• Journal Title: Cancer
• Volume: Volume 124, Number 15
• Publisher: Wiley: 12 months | 2018-08-01, Pages 3163-3170
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cncr.31537
• Subjects: Health Sciences, Oncology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; fatigue; head and neck cancer; human papillomavirus (HPV); inflammation; QUALITY-OF-LIFE; PHASE-3 RANDOMIZED-TRIAL; RADIATION PLUS CISPLATIN; LOCALLY ADVANCED HEAD; CONCURRENT CHEMORADIOTHERAPY; OROPHARYNGEAL CANCER; PERFORMANCE STATUS; RADIOTHERAPY; DEPRESSION; SURVIVORS

Abstract

BACKGROUND: Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation. METHODS: Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy. Fatigue was measured using the Multidimensional Fatigue Inventory. Peripheral inflammation was assessed by plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2), and IL-6. Mixed effect models were used to examine associations. RESULTS: A total of 94 patients who were newly diagnosed were enrolled; 53% had HPV-related tumors. Patients with HPV-unrelated tumors had higher fatigue and higher plasma CRP, sTNFR2, and IL-6 over time, especially at baseline and 3 months after intensity-modulated radiotherapy compared with those with HPV-related tumors (all P <.05). However, fatigue and plasma sTNFR2 increased more significantly from baseline to 1 month after radiotherapy in the HPV-related group compared with the HPV-unrelated group (both P <.01). Controlling for significant covariates, HPV status and inflammation were found to be independent predictors of fatigue over time. CONCLUSIONS: HPV status is an important marker of vulnerability to the behavioral and immune consequences of SCCHN and its treatment, providing support for different symptom management strategies. Special emphasis should be placed on addressing marked persistent fatigue in patients with HPV-unrelated tumors, whereas attention should be paid to the large increases in fatigue during treatment among patients with HPV-related tumors.