Human papillomavirus (HPV) infection has recently been linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and progression are poorly understood. Methods: We performed MS-based proteomics profiling based on HPV status in OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (−) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival, in contrast to A2M and Serpine1, low levels of which show an association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rates, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor that, when activated, triggered the S100A8 and NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (−), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses, which has important consequences in prognosis and may guide therapeutic decisions.

Background We report an unusual case of metastatic colon adenocarcinoma to the maxilla as an initial clinical sign of the disease, this being the second case reported in the palate. In addition, we show an extensive review of the literature, with clinical cases of adenocarcinoma with metastasis to the mouth. Case presentation An 80-year-old man complained of “swelling on the palate” with a 3-week evolution time. He reported suffering from constipation and high blood pressure. The intraoral examination revealed a pedunculated, red, and painless nodule on the maxillary gingiva. Under the diagnostic hypotheses of squamous cell carcinoma and malignant neoplasm of the salivary gland, an incisional biopsy was performed. Microscopically, the columnar epithelium was observed forming papillary areas, neoplastic cells with prominent nucleoli, hyperchromatic nuclei, atypical mitotic figures, and mucous cells, being positive for CK 20, suggesting the provisional diagnosis of metastatic adenocarcinoma, probably of gastrointestinal origin. The patient was submitted to endoscopy and colonoscopy exams, and a lesion in the sigmoid region of the colon was observed. After a colon biopsy, a moderately differentiated adenocarcinoma was confirmed, establishing the final diagnosis of metastatic neoplasia of colon adenocarcinoma to the oral lesion. The literature review revealed 45 clinical cases of colon adenocarcinoma with metastasis to the oral cavity. To the best of our knowledge, it is the second case on the palate. Conclusions Colon adenocarcinoma with metastasis to the oral cavity is rare but should be included in the differential diagnosis of neoplasms of the oral cavity, even when there are no known primary tumors in some cases, and this may be the first indication of the presence of a tumor.

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