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Follow-up comparisons of significant overall models indicated that rural patients reported significantly more nonsomatic depression symptoms at 6-month follow-up. Rural patients were also more likely to report significantly poorer general mental HRQOL at 12-month follow-up, significantly poorer HNC-specific HRQOL related to eating at 6- and 12-month follow-up, and marginally worse aesthetics at 12-month follow-up. These findings are consistent with suggestions that rural HNC patients may be at heightened risk for depression symptoms and decrements in HRQOL.