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Research ArticleHead & Neck
Open Access

Diffusion-Weighted Imaging to Assess HPV-Positive versus HPV-Negative Oropharyngeal Squamous Cell Carcinoma: The Importance of b-Values

V. Lenoir, B.M.A. Delattre, Y. M'RaD, C. De Vito, T. de Perrot and M. Becker
American Journal of Neuroradiology June 2022, 43 (6) 905-912; DOI: https://doi.org/10.3174/ajnr.A7521
V. Lenoir
aFrom the Division of Radiology (V.L., B.M.D., Y.M., T.d.P., M.B.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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B.M.A. Delattre
aFrom the Division of Radiology (V.L., B.M.D., Y.M., T.d.P., M.B.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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Y. M'RaD
aFrom the Division of Radiology (V.L., B.M.D., Y.M., T.d.P., M.B.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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C. De Vito
bDivision of Clinical Pathology (C.D.V.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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T. de Perrot
aFrom the Division of Radiology (V.L., B.M.D., Y.M., T.d.P., M.B.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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M. Becker
aFrom the Division of Radiology (V.L., B.M.D., Y.M., T.d.P., M.B.), Diagnostic Department, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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  • FIG 1.
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    FIG 1.

    ADC histogram changes caused by b-value choice illustrated in 2 different patients with OPSCC. T2 and corresponding b=1000 images with tumor ROIs (in yellow) are shown on the left side of the figure. The histograms in blue were obtained from the pixel values of the HPV+ OPSCC ROI, and the histograms in orange, from the pixel values of the HPV– OPSCC ROI. ADC mean values are indicated in blue for the HPV+ OPSCC and in red for the HPV– OPSCC, respectively. On ADC maps with b=0, HPV+ OPSCC histograms have lower ADC mean values, a slender peak (leptokurtic shape), and a right skew, whereas HPV– OPSCC histograms have higher ADC mean values, lower kurtosis (flatter shape), and a more symmetric shape (Gaussian distribution). On ADC maps with b=0, the histograms of the 2 tumors can be easily distinguished one from another. This is hardly possible on perfusion-insensitive ADC maps (ADCb100-1000, ADCb500-1000, ADCb750-1000) due to overlapping metrics.

  • FIG 2.
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    FIG 2.

    Color-coded maps in 2 different patients with OPSCC (same patients as in Fig 1) illustrating changes in ADC pixel values and distribution caused by the choice of b-values. T2 images and corresponding b=1000 images with tumor ROIs (in yellow) are shown on the left. The upper 2 rows on the right show the color-coded ADC maps of the HPV+ OPSCC, while the lower 2 rows show the respective maps of the HPV– OPSCC. For all images, the same color map with the same quantitative scale (0–3000 ×10−6mm2/s) was used to display the original gray levels. Note the clearly visible difference between HPV+ versus HPV– OPSCC on the ADC maps with b=0, with HPV+ OPSCC having lower ADCs and less ROI heterogeneity than HPV– OPSCC. This difference disappears on maps calculated with higher b-values only, and the distinction between the 2 tumor types is visually hardly possible on maps calculated with b ≥ 500. The 2 readers correctly identified the HPV+ and the HPV– OPSCC on the first 7 ADC maps; they failed, however, to correctly distinguish between the 2 tumor types on the last 2 ADC maps.

Tables

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    Table 1:

    Choice of b-values for each calculated ADC map

    No. of b-ValuesUsed b-ValuesMonoexponential Model
    201000ADCb0–1000
    40501001000ADCb0–50–100–1000
    50501007501000ADCb0–50–100–750–1000
    60501005007501000ADCb0–50–100–500–750–1000
    307501000ADCb0–750–1000
    405007501000ADCb0–500–750–1000
    21001000ADCb100–1000
    25001000ADCb500–1000
    27501000ADC b750–1000
    • View popup
    Table 2:

    Patient and tumor characteristics

    HPV– OPSCC (n = 23)HPV+ OPSCC (n = 11)P Value
    Average age (range) (yr)62 (50–82)62 (48–85).986a
    Sex
        Women7 (7/23, 30%)6 (6/11, 55%)
        Men16 (16/23, 70%)5 (5/11, 45%).329b
    Tumor location
        Oropharynx23 (23/23, 100%)11 (11/11, 100%)
    T classification according to AJCC 20184,5.944c
        T13 (3/23, 13%)0 (0/11, 0%)
        T23 (3/23, 13%)2 (2/11, 18%)
        T35 (5/23, 22%)2 (2/11, 18%)
        T412 (12/23, 52%)7 (7/11, 64%)
    N classification according to AJCC 20184,5.138c
        N05 (5/23, 22%)0 (0/11, 0%)
        N13 (3/23, 13%)5 (5/11, 45%)
        N215 (15/23, 65%)6 (6/11, 55%)
        N30 (0/23, 0%)0 (0/11, 0%)
    M classification according to AJCC 20184,5.630c
        M022 (22/23, 96%)11 (11/11, 100%)
        M11 (1/23, 4%)0 (0/11, 0%)
    Tumor keratinization at histopathology.140b
        Present14 (14/23, 61%)7 (7/11, 64%)
        Absent9 (9/23, 39%)4 (4/11, 36%)
    Mean proliferation index, MIB-1 (range) (%)55 (15–90)69 (50–90).126d
    • ↵a T test.

    • ↵b Pearson χ2 test.

    • ↵c Fisher exact test.

    • ↵d Mann-Whitney-Wilcoxon test.

    • View popup
    Table 3:

    Comparison of ADC histograms in HPV+ versus HPV– OPSCC for each b-value combinationa

    HPV– OPSCCHPV+ OPSCCP Valueb
    ADC Meanc
        ADCb0–10001117 (SD, 151)977 (SD, 183).038
        ADCb0–50–100–10001029 (SD, 176)924 (SD, 185).164
        ADCb0–50–100–750–10001051 (SD, 168)925 (SD, 176).077
        ADCb0–50–100–500–750–10001061 (SD, 167)935 (SD, 176).084
        ADCb0–750–10001141 (SD, 156)983 (SD, 177).017
        ADCb0–500–750–10001127 (SD, 156)970 (SD, 177).017
        ADCb100–1000947 (SD, 245)875 (SD, 206).214
        ADCb500–1000838 (SD, 255)758 (SD, 287).176
        ADCb750–1000900 (SD, 360)942 (SD, 340).942
    Skewness
        ADCb0–10000.156 (SD, 0.453)0.486 (SD, 0.444).031
        ADCb0–50–100–10000.266 (SD, 0.442)0.393 (SD, 0.48).258
        ADCb0–50–100–750–10000.331 (SD, 0.526)0.363 (SD, 0.609).445
        ADCb0–50–100–500–750–10000.31 (SD, 0.542)0.363 (SD, 0.649).383
        ADCb0–750–10000.177 (SD, 0.518)0.506 (SD, 0.483).046
        ADCb0–500–750–10000.2 (SD, 0.496)0.499 (SD, 0.458).034
        ADCb100-10000.136 (SD, 0.427)0.069 (SD, 0.486).468
        ADCb500–10000.229 (SD, 0.431)0.103 (SD, 0.47).537
        ADCb750–10000.672 (SD, 0.739)0.435 (SD, 0.383).214
    Excess kurtosis
        ADCb0–10000.12 (SD, 0.71)1.22 (SD, 0.45)< .001
        ADCb0–50–100–10000.34 (SD, 0.81)1.36 (SD, 0.69)< .001
        ADCb0–50–100–750–10000.57 (SD, 1.25)1.64 (SD, 1.15).008
        ADCb0–50–100–500–750–10000.55 (SD, 1.25)1.74 (SD, 1.23).007
        ADCb0–750–10000.21 (SD, 0.81)1.22 (SD, 0.58).002
        ADCb0–500–750–10000.2 (SD, 0.84)1.19 (SD, 0.53).002
        ADCb100–10000.51 (SD, 1.2)1.22 (SD, 1.09).019
        ADCb500–10000.19 (SD, 0.84)0.7 (SD, 1.1).188
        ADCb750–10000.76 (SD, 2.18)0.3 (SD, 1.09).942
    • ↵a Data are means.

    • ↵b Mann-Whitney-Wilcoxon test.

    • ↵c Units in ×10−6mm2/s.

    • View popup
    Table 4:

    Diagnostic performance of ADC maps capable of distinguishing HPV+ from HPV– OPSCC on the basis of ADC mean, skewness, and kurtosisa

    FeatureAUCP ValueTPFPTNFNSensitivitySpecificityAccuracyOptimal Threshold
    ADCb0–1000
        ADC mean0.723.019871630.7270.6950.7061062.429b
        ADC skewness0.731.016861730.7270.7390.7350.349
        ADC kurtosisc0.893<.0011141901.0000.8260.8820.640
    ADCb0–750–1000
        ADC mean0.755.009871630.7270.6950.7061088.702b
        ADC skewness0.715.023851830.7270.7830.7650.500
        ADC kurtosisc0.826.0011051810.9090.7830.8230.651
    ADCb0–500–750–1000
        ADC mean0.755.009851830.7270.7830.7651034.222b
        ADC skewness0.727.009841930.7270.8260.7940.525
        ADC kurtosisc0.826.0011051810.9090.7830.8230.620
    ADCb100–1000
        ADC mean0.636.105881530.7270.6520.676958.089b
        ADC skewness0.581.231791440.6360.6090.6180.133
        ADC kurtosisc0.751.010971620.8180.6960.7350.484
    • Note:—TP indicates true-positive; FP, false-positive; TN, true-negative; FN, false-negative.

    • ↵a For comparison, the diagnostic performance of the perfusion-insensitive map recommended in the literature14 is equally shown. P values to distinguish HPV+ from HPV– OPSCC were calculated with the Mann-Whitney-Wilcoxon test. Sensitivity, specificity, and accuracy were calculated using the optimal threshold (Youden index from receiver operating curve analysis).

    • ↵b ADC mean thresholds in x10−6mm2/s.

    • ↵c Excess kurtosis.

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American Journal of Neuroradiology: 43 (6)
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V. Lenoir, B.M.A. Delattre, Y. M'RaD, C. De Vito, T. de Perrot, M. Becker
Diffusion-Weighted Imaging to Assess HPV-Positive versus HPV-Negative Oropharyngeal Squamous Cell Carcinoma: The Importance of b-Values
American Journal of Neuroradiology Jun 2022, 43 (6) 905-912; DOI: 10.3174/ajnr.A7521

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DWI for HPV-Positive vs. HPV-Negative Carcinoma
V. Lenoir, B.M.A. Delattre, Y. M'RaD, C. De Vito, T. de Perrot, M. Becker
American Journal of Neuroradiology Jun 2022, 43 (6) 905-912; DOI: 10.3174/ajnr.A7521
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