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HPV status of head, neck cancer influences fatigue, inflammation

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July 17, 2018

Patients with HPV-unrelated squamous cell carcinoma of the head and neck experienced greater fatigue and inflammation at baseline and over time than patients with HPV-related tumors, according to results of a longitudinal, prospective study.

However, patients with HPV-related tumors experienced a greater increase in fatigue during the first month of radiotherapy.

“The incidence of HNSCC has been consistently increasing in the United States, due mainly to the increased incidence of HPV infection. Patients with HPV-related HNSCC have better responses to treatment and better survival than patients with HPV-unrelated HNSCC,” Canhua Xiao RN, PhD, assistant professor at Nell Hodgson Woodruff School of Nursing at Emory University, and colleagues wrote. “However, to the best of our knowledge, studies to date have not explored the association between HPV status and cancer-related fatigue and whether HPV status plays a role in biological mechanisms related to fatigue, including inflammation.”

Xiao and colleagues explored the associations between HPV and fatigue among 94 patients (mean age, 58 years; 88% white; 75% men) with HNSCC without distant metastasis who underwent intensity-modulated radiotherapy at Emory University radiation clinics. About 77% of patients received concurrent chemotherapy.

Researchers assessed patients at baseline and 1 month and 3 months after radiotherapy.

The investigators used the Multidimensional Fatigue inventory to measure fatigue with a total score ranging from 20 to 100, where higher scores indicated more fatigue. They measured plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2) and IL-6 to evaluate peripheral inflammation.

Fifty-three percent of patients had HPV-related tumors.

Patients with HPV-related tumors appeared more likely:

  • to be male (P = .033);
  • have no history of tobacco use (P = .002);
  • have a higher BMI (P = .028);
  • be diagnosed with oropharyngeal cancer (P < .0001);
  • receive concurrent chemoradiotherapy (P < .0001); and
  • receive higher dose of radiotherapy (P < .0001).

Patients with HPV-unrelated tumors appeared more likely to have worse fatigue over the course of the study than patients with HPV-related tumors (P = .0097). Researchers observed these associations over time, but especially at baseline (mean, 50.93 vs. 40.6; P = .001) and 3 months after IMRT (mean, 59.88 vs. 45.47; P = .002).

Patients with HPV-unrelated tumors also appeared to have higher plasma CRP (P < .0001), sTNFR2 (P = .0369) and IL-6 (P = .0064).

Researchers did not observe significant associations between HPV status and serum IL-1ra.

HPV status and inflammation — but not treatment type or receipt of chemotherapy or surgery — appeared to be independent predictors of fatigue over time.

Patients with HPV-related tumors experienced larger increases in fatigue and inflammation from baseline to 1-month post-IMRT, and larger decreases from 1 month to 3 months following IMRT, than patients with HPV-unrelated tumors.

“Given the similar intensive treatment regimens received by both groups at the time of the current study, this larger increase in fatigue and inflammation indicates that patients with HPV-related disease are more likely to be affected by treatment intensity, further supporting the rationale for current dose reduction trials in patients with HPV-related HNSCC,” the researchers wrote.

Limitations of the study included missing data at 3 months postradiotherapy, potential cofounders for fatigue and inflammation, and the heterogenous nature of head and neck cancer sites.

“These different symptom profiles suggest that clinicians may want to use different symptom management strategies for patients with or without HPV-related tumors,” Xiao and colleagues wrote. “More specifically, patients with HPV-unrelated disease need constant support before and after treatment, whereas the 1-month post-IMRT time point is when patients with HPV-related tumors need the most attention.” – by Cassie Homer

Disclosures: The authors report no relevant financial disclosures.