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Page 2 of 13                              Salas et al. J Cancer Metastasis Treat 2018;4:15  I  http://dx.doi.org/10.20517/2394-4722.2017.66


               Keywords: P16, head, neck, maxilla, prognosis, survival




               INTRODUCTION
                                                                                              [1]
               Squamous cell carcinomas (SCC) of the hard palate and upper alveolus ridge are relatively rare . Prognostic
               factors and neck management in head and neck SCC (HNSCC) have been extensively studied in series of
                                                                                   [2]
               tongue or floor of mouth SCC, or on series with a mixture of SCC tumor sites . Only small retrospective
               series have evaluated the behavior of hard palate and upper alveolus, and suggest that they have a low rate of
                                    [3-8]
               regional node metastases . However, recent studies find higher rates of both neck lymph node involvement
               and neck recurrence in these malignancies, and, there is a need to identify those aggressive cases that would
               benefit from more aggressive treatment [9,10] .

               Several clinicopathological features have been implicated in recurrence risk and prognosis in HNSCC.
               These include tumor size, nodal involvement, tobacco and alcohol consumption, and presence of human
               papillomavirus (HPV) infection [11,12] .

               The prevalence of HPV infection is higher in oropharyngeal squamous cell carcinoma (OPSCC) (35.6%) and
               has been associated with both better prognosis and higher response rate to chemoradiation [12,13] . P16 staining
               is highly correlated with HPV infection in OPSCC and has also been associated with good prognosis [14-17] .
               There is no information about the rate of p16 expression in rare locations like hard palate and upper alveolar
               ridge.

               The aim of the present study was to evaluate predictive factors associated with node involvement, prognostic
               factors, and prevalence of p16 staining in hard palate and upper alveolar ridge SCC.


               METHODS
               Study population
               All patients treated at Department of Head and Neck at Instituto Nacional de Enfermedades Neoplasicas
               with maxillary SCC between January 1997 and December 2011 were screened for the study. Inclusion criteria
               included having a primary tumor located in the upper alveolar ridge or hard palate, having a squamous
               histology, and having history of resection of primary tumor. Patients with primary tumor of nasal cavity and
               paranasal sinuses were excluded. The procedure of neck management was selected by the Institute surgeon.
               It included neck dissection in cases of clinically involved lymph nodes and in cases of metastasis risk factors
               like greater depth of primary tumor deep invasion. Selection of ipsilateral or bilateral dissection was also
               determined by the Institute surgeon and took into account clinical factors like proximity to midline.


               Information about clinicopathological variables was taken from patient files and pathology report. Data
               included age, gender, tobacco use, alcohol use, tumor subsite, depth of invasion, histologic grade, margin
               status, perineural invasion (PNI), lymphovascular invasion (LVI), clinical and pathological stage (TNM
               classification), surgical procedure, radiation or chemotherapy administration, and date of last follow-
               up or death. Some standard pathological features that were not reported in patient file were prospectively
               completed by a pathologist (LC). The institutional review board approval was obtained from The Instituto
               Nacional de Enfermedades Neoplasicas (Lima, Peru). Since the study was based on a secondary source and
               there was no contact with the patients, no informed consent was applied; however, the identity and personal
               data of patients’ medical records were protected at all times.


               P16 immunohistochemistry assay
               Pathologists evaluated H&E slides under light microscopy and the most representative tissue were selected.
               A 0.6-cm punch was taken from each formalin-fixed paraffin-embedded (FFPE) sample selected and was
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