Apparent Diffusion Coefficient Histograms of Human Papillomavirus-Positive and Human Papillomavirus-Negative Head and Neck Squamous Cell Carcinoma: Assessment of Tumor Heterogeneity and Comparison with Histopathology

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma associated with human papillomavirus infection represents a distinct tumor entity. We hypothesized that diffusion phenotypes based on the histogram analysis of ADC values reflect distinct degrees of tumor heterogeneity in human papillomavirus-positive and human papillomavirus-negative head and neck squamous cell carcinomas. MATERIALS AND METHODS: One hundred five consecutive patients (mean age, 64 years; range, 45-87 years) with primary oropharyngeal (n = 52) and oral cavity (n = 53) head and neck squamous cell carcinoma underwent MR imaging with anatomic and diffusion-weighted sequences (b = 0, b = 1000 s/mm(2), monoexponential ADC calculation). The collected tumor voxels from the contoured ROIs provided histograms from which position, dispersion, and form parameters were computed. Histogram data were correlated with histopathology, p16-immunohistochemistry, and polymerase chain reaction for human papillomavirus DNA. RESULTS: There were 21 human papillomavirus-positive and 84 human papillomavirus-negative head and neck squamous cell carcinomas. At histopathology, human papillomavirus-positive cancers were more often nonkeratinizing (13/21, 62%) than human papillomavirus-negative cancers (19/84, 23%; P = .001), and their mitotic index was higher (71% versus 49%; P = .005). ROI-based mean and median ADCs were significantly lower in human papillomavirus-positive (1014 +/- 178 x 10(-6) mm(2)/s and 970 +/- 187 x 10(-6) mm(2)/s, respectively) than in human papillomavirus-negative tumors (1184 +/- 168 x 10(-6) mm(2)/s and 1161 +/- 175 x 10(-6) mm(2)/s, respectively; P < .001), whereas excess kurtosis and skewness were significantly higher in human papillomavirus-positive (1.934 +/- 1.386 and 0.923 +/- 0.510, respectively) than in human papillomavirus-negative tumors (0.643 +/- 0.982 and 0.399 +/- 0.516, respectively; P < .001). Human papillomavirus-negative head and neck squamous cell carcinoma had symmetric normally distributed ADC histograms, which corresponded histologically to heterogeneous tumors with variable cellularity, high stromal component, keratin pearls, and necrosis. Human papillomavirus-positive head and neck squamous cell carcinomas had leptokurtic skewed right histograms, which corresponded to homogeneous tumors with back-to-back densely packed cells, scant stromal component, and scattered comedonecrosis. CONCLUSIONS: Diffusion phenotypes of human papillomavirus-positive and human papillomavirus-negative head and neck squamous cell carcinomas show significant differences, which reflect their distinct degree of tumor heterogeneity.