Correlation of Cellular Immunity With Human Papillomavirus 16 Status and Outcome in Patients With Advanced Oropharyngeal Cancer

Objective: To determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's adaptive immunity. Setting: Academic medical center. Patients: Forty-seven of 66 previously untreated patients (6 of 20 patients with stage III and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy. Intervention: All patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy. Main Outcome Measures: Pretreatment levels (percentages and absolute counts) of CD3, CD4, CD8, natural killer, and B cells and overall white blood cell counts were measured by flow cytometry. Correlations of subsets with HPV-16 status, tumor subsite, cancer stage, T class, N class, smoking status, performance status, sex, response to chemoradiotherapy, p53 mutation type, epidermal growth factor receptor expression, and disease-specific and overall survival were determined. Results: After a median follow-up of 6.6 years, improved survival was associated with an elevated percentage of CD8 cells (P=.04), a low CD4:CD8 ratio (P=.01), low epidermal growth factor receptor expression (P=.002), and HPV status (P=.02). The percentage of CD8 cells was significantly higher (P=.04) and the CD4:CD8 ratio was significantly lower (P=.02) in HPV-16 positive patients. A higher percentage of CD8 cells was associated with response to induction chemotherapy (P=.02) and complete tumor response after chemoradiotherapy (P=.045). Conclusion: These findings confirm previous correlations of outcome with circulating CD8 cell levels and support the conjecture that improved adaptive immunity may play a role in the favorable prognosis of patients with HPV-16-positive cancers. Arch Otolaryngol Head Neck Surg. 2010;136(12):1267-1273