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Salas et al. J Cancer Metastasis Treat 2018;4:15  I  http://dx.doi.org/10.20517/2394-4722.2017.66                              Page 5 of 13


                             Table 2. Relationship between clinicopathological features and lymph node involvement
                                                            Neck lymph node (%)          P
                                                    Negative (n = 59)  Positive (n = 19)
                            Age (years), mean (range)   65.41 (31-89)  61.58 (21-88)    0.329
                            Location
                              Upper alveolus          56 (94.9)        17 (89.5)
                              Hard palate             3 (5.1)          2 (10.5)         0.590
                            cT
                              T2-T3                   19 (32.2)        5 (26.3)
                              T4                      40 (67.8)        14 (73.7)        0.629
                            Grade
                              Poor/moderate differentiation  24 (40.7)  10 (52.6)
                              Well differentiated     35 (59.3)        9 (47.4)         0.361
                            PNI
                              No                      23 (60.5)        8 (57.1)
                              Yes                     15 (39.5)        6 (42.9)         0.825
                            LVI
                              No                      32 (82.1)        8 (57.1)
                              Yes                     7 (17.9)         6 (42.9)         0.080
                            Tobacco
                              No                      53 (89.8)        17 (89.5)
                              Yes                     6 (10.2)         2 (10.5)         1.000
                            Alcohol
                              No                      55 (93.2)        18 (94.7)
                              Yes                     4 (6.8)          1 (5.3)          1.000
                            p16
                              Negative                30 (90.9)        8 (100.0)
                              Positive                3 (9.1)          0 (0.0)          -

                                          PNI: perineural invasion; LVI: lymphovascular infiltration

               (n = 2), chemotherapy alone (n = 2) or no-treatment (n = 4). Cervical metastases in these 18 cases of cervical
               recurrences were distributed between levels I (61.1%), II (100%) and III (27.8%).

               Fourteen of the patients who were clinically node-negative (25.9%) and 4 of the patients who were
               pathologically confirmed node-positive at presentation (16.7%) had recurrences in the neck. The mean
               time to neck recurrence was 8.6 months (2 to 29 months). A factor associated with neck failure was high
               histological grade (P = 0.037). Recurrences were not associated with age (P = 0.725), cT (P = 0.754), N (P =
               0.536), or PNI (P = 0.624) [Table 3].

               Expression of p16
               A total of 41 (52.5%) lesions were tested for p16 expression. Overall, 7.3% (3 of 41) were p16 positive: 1 of
               2 in hard palate (50%) and 2 of 39 in alveolar ridge (5.1%) [Figure 1]. The p16 positive tumors were not
               associated with age (P = 0.067), tumor location (P = 0.143), cT (P = 1.000), or histological grade (P = 0.560)
               [Table 4].

               Survival analysis
               Median overall survival (OS) was 40 months. Neither smoking nor alcohol consumption was associated with
               shorter disease-free survival (DFS) (P = 0.815 and 0.507) nor OS (P = 0.597 and 0.634). LVI (P = 0.026) was
               associated with shorter DFS in univariate analysis. Larger cT (P = 0.019), presence of PNI (P = 0.039), LVI (P
               = 0.021), and neck dissection (P = 0.010) were associated with shorter OS in univariate analysis [Figure 2].
               Neck involvement had a trend both for shorter DFS (31% vs. 48.7%, P = 0.278) and shorter OS (25.1% vs.
               48.5%, P = 0.340). There was also a trend to shorter OS (9.3% vs. 52.3%, P = 0.064) in the presence of neck
               recurrence [Table 5].
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