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Research ArticleHead and Neck Imaging
Open Access

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

T. de Perrot, V. Lenoir, M. Domingo Ayllón, N. Dulguerov, M. Pusztaszeri and M. Becker
American Journal of Neuroradiology November 2017, 38 (11) 2153-2160; DOI: https://doi.org/10.3174/ajnr.A5370
T. de Perrot
aFrom the Division of Radiology, Department of Imaging and Medical Informatics (T.d.P., V.L., M.D.A., M.B.)
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V. Lenoir
aFrom the Division of Radiology, Department of Imaging and Medical Informatics (T.d.P., V.L., M.D.A., M.B.)
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M. Domingo Ayllón
aFrom the Division of Radiology, Department of Imaging and Medical Informatics (T.d.P., V.L., M.D.A., M.B.)
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N. Dulguerov
bDivision of Head and Neck Surgery, Department of Clinical Neurosciences (N.D.)
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M. Pusztaszeri
cDivision of Clinical Pathology, Department of Genetic and Laboratory Medicine (M.P.), Geneva University Hospitals, Geneva, Switzerland.
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M. Becker
aFrom the Division of Radiology, Department of Imaging and Medical Informatics (T.d.P., V.L., M.D.A., M.B.)
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  • Fig 1.
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    Fig 1.

    Box plots for mean ADC, median ADC, excess kurtosis, and skewness from ROIs obtained in 105 tumors (84 HPV− HNSCC and 21 HPV+ HNSCC). Horizontal lines indicate median values (black lines). The bottom and the top of the box are the first and third quartiles whereas whiskers indicate maximum and minimum values. Outliers are indicated by circles.

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    Fig 2.

    A 59-year-old womam with HPV− HNSCC (T2N0M0). A, T2-weighted image reveals a left tonsillar tumor (arrow) with intermediate signal intensity. B, B1000 and C, gray-scale ADC map show restricted tumor diffusion (arrows). The freehand ROI contoured on the ADC map is visible as a blue line. D, On the color-coded ADC map (same level as C), tumor heterogeneity (purple and various shades of blue-green areas within the tumor) is more easily appreciated than in C. E, Histology (hematoxylin-eosin; original magnification, 200X) shows heterogeneous tumor matrix with areas of densely packed and loosely packed squamous cells of variable size. Variable amounts of keratin pearls (asterisk) and necrosis were present in this tumor. F, Immunohistochemistry for p16 (original magnification, 200X) is negative (ie, most cells show no brownish coloration).

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    Fig 3.

    A 60-year-old man with HPV+ HNSCC (T3N2M0). A, T2-weighted image reveals a left tonsillar tumor (long arrow) with intermediate signal intensity, parapharyngeal space invasion, and bilateral retropharyngeal lymph node metastases (short arrows). B, B1000 and C, gray-scale ADC map show restricted diffusion within the tonsillar tumor (long arrows) and within the lymph node metastases (short arrows). The freehand ROI contoured on the gray-scale ADC map is visible as a blue line. D, Color-coded ADC map (same level as C). Note that this tumor is less heterogeneous (mainly blue areas) than the tumor in Fig 1. E, Histology (hematoxylin-eosin; original magnification, 200×) shows homogeneous tumor consisting of clusters of densely packed, basaloid cells with scant cytoplasm, and without keratinization. Focal necrosis in the center of the tumor cell clusters (comedonecrosis) is present (asterisk). F, Immunohistochemistry for p16 is positive; more than 70% of tumor cells show strong cytoplasmic and nuclear staining indicating HPV positivity (original magnification, 200×). Polymerase chain reaction for HPV DNA further confirmed HPV positivity.

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    Fig 4.

    Characteristic histograms obtained in 2 different patients with HNSCC of the base of the tongue. Patient A (T4N2M0) has an HPV+ HNSCC (gray histogram) and patient B (T4N2M0) has an HPV− cancer (blue histogram). Red lines correspond to the median value of each histogram. Yellow lines correspond to the mean value of each histogram. Note that the histogram in the HPV− cancer (blue histogram) is symmetric with widely distributed ADC values around the central line (Gaussian distribution), whereas the histogram in the HPV+ HNSCC (gray histogram) shows asymmetric distribution of ADC values with a right thicker tail (right skew) and an elongated aspect (leptokurtic shape) because a larger proportion of voxel values are located in a narrow band. The mean ADC in HPV+ HNSCC is farther away from the median ADC value (distribution skewed to the right) than in the HPV− histogram.

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    Table 1:

    Patienta and tumor characteristics

    CharacteristicsHPV− HNSCC (n = 84)HPV+ HNSCC (n = 21)P Valueb
    Average age (range), yr65 (45–87)61 (45–73).15c
    Sex, no. (%)
        Women23 (27)7 (33)
        Men61 (73)14 (67).79d
    Tumor location, no. (%)
        Oral cavity50 (60)3 (14)
        Oropharynx34 (40)18 (86)<.001d
    T classification according to AJCC 2017, no. (%)f
        T15 (6)1 (5)
        T222 (26)6 (29)
        T315 (18)3 (14)
        T442 (50)11 (52)1e
    N classification according to AJCC 2017, no. (%)
        N036 (43)4 (19)
        N113 (15)6 (29)
        N235 (42)9 (43)
        N30 (0)2 (9).012e
    M classification according to AJCC 2017, no. (%)
        M077 (92)18 (86)
        M11 (1)1 (5)
        Mx6 (7)2 (9).47e
    Tumor keratinization, no. (%)
        Present65 (77)8 (38)
        Absent19 (23)13 (62).001d
    Degree of keratinization, no. (%)
        Keratinizing48 (57)3 (14)
        Focally keratinizing17 (20)5 (24)<.001e
        Nonkeratinizing, no. (%)19 (23)13 (62)
    Histologic differentiation, no. (%)
        Well differentiated15 (18)Not assessablef
        Moderately differentiated48 (57)
        Poorly differentiated21 (25)
    Semiquantitative histologic score, no. (%)g
        Score 1 (most heterogeneous)14 (17)0 (0)
        Score 28 (9)0 (0)
        Score 341 (49)7 (33).002e
        Score 412 (14)5 (24)
        Score 5 (most homogeneous)9 (11)9 (43)
    Mean proliferation index, MIB-1 (%)h4971.005c
        Range in %8–9030–95
    • Note:—AJCC indicates American Joint Committee on Cancer.

    • ↵a Total patients, 105.

    • ↵b P values are indicated for the comparisons between HPV+ and HPV− HNSCCs.

    • ↵c Wilcoxon rank sum test.

    • ↵d Pearson χ2 test.

    • ↵e Fisher test.

    • ↵f HPV+ HNSCC was not graded according to AJCC 2017 guidelines.3

    • ↵g The semiquantitative histologic score is described in On-line Table 1.

    • ↵h Available in 95 histologic samples.

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    Table 2:

    Quantitative ADC parameters from histogram analysis of tumors in the oropharynx and oral cavity at 1.5T and 3T and for all tumors together irrespective of field strength (pooled data)

    Histogram-Based ADC Parameters1.5T (n = 45)3T (n = 60)Pooled Data (n = 105)
    HPV− (n = 33) (mean ± SD)HPV+ (n = 12) (mean ± SD)P ValueaHPV− (n = 51) (mean ± SD)HPV+ (n = 9) (mean ± SD)P ValueaHPV− (n = 84) (mean ± SD)HPV+ (n = 21) (mean ± SD)P Valuea
    Mean ADC (× 10−6 mm2/s)1158 ± 183989 ± 188.0041201 ± 1571046 ± 167.021184 ± 1681014 ± 178<.001
    Median ADC (×10−6 mm2/s)1135 ± 193936 ± 198.0031177 ± 1621016 ± 170.031161 ± 175970 ± 187<.001
    Minimum ADC (× 10−6 mm2/s)422 ± 251379 ± 172.36441 ± 238286 ± 207.10433 ± 242339 ± 188.09
    25 Quartile (× 10−6 mm2/s)977 ± 162813 ± 172.0081004 ± 151900 ± 165.13993 ± 155850 ± 171<.001
    75 Quartile (× 10−6 mm2/s)1318 ± 2161115 ± 219.0031374 ± 1831163 ± 180.0051352 ± 1971136 ± 200<.001
    Interquartile range (× 10−6 mm2/s)341 ± 111302 ± 79.33371 ± 114263 ± 68.003359 ± 113285 ± 75.003
    Skewness0.362 ± 0.6471.012 ± 0.546.0040.424 ± 0.4160.804 ± 0.461.020.399 ± 0.5160.923 ± 0.510<.001
    Excess kurtosis0.841 ± 0.1161.728 ± 1.250.030.514 ± 0.8722.207 ± 1.583.0010.643 ± 0.9821.934 ± 1.386<.001
    • ↵a P values (Wilcoxon rank sum test) are indicated for the comparisons between HPV+ and HPV− HNSCCs.

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American Journal of Neuroradiology: 38 (11)
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T. de Perrot, V. Lenoir, M. Domingo Ayllón, N. Dulguerov, M. Pusztaszeri, M. Becker
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
American Journal of Neuroradiology Nov 2017, 38 (11) 2153-2160; DOI: 10.3174/ajnr.A5370

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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
T. de Perrot, V. Lenoir, M. Domingo Ayllón, N. Dulguerov, M. Pusztaszeri, M. Becker
American Journal of Neuroradiology Nov 2017, 38 (11) 2153-2160; DOI: 10.3174/ajnr.A5370
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