BACKGROUND: p16 has often been found to be overexpressed in patients oral squamous cell carcinoma (OSCC), but its prognostic value between anatomic subsites is still unclear.
OBJECTIVE: The aim of this study was to investigate the diagnostic and prognostic values of p16 in OSCC originating from tongue, gingiva or buccal mucosa.
METHODS: A total of 147 OSCC patients with tumors arising from the tongue, gingiva or buccal mucosa were enrolled in this study. p16 expression was detected using immunohistochemistry (IHC), and the presence of HPV16 was determined by real-time PCR in p16 positive patients. The correlation of p16 expression with the clinical parameters was evaluated.
RESULTS: Only one p16 positive patient with a cut off value of 25% and 75% was HPV16 positive. Although overall survival (OS), recurrence free survival (RFS) and metastasis free survival (MFS) had no significant differences between the p16 positive and negative patients, p16 negative patients (cut off value 25%) had more RFS in the buccal mucosa cancer (p= 0.03) than the p16-positive patients.
CONCLUSIONS: The prevalence of HPV16 in Chinese OSCC patients was low. p16 overexpression decoupled from HPV infection was not a prognostic marker for OSCC patients except for patients with the buccal mucosa cancer.

Oral papillary squamous cell carcinoma (PSCC) is an unusual variant of squamous cell carcinoma with a better prognosis. The most common location of PSCC in the oral cavity is the gingiva and buccal mucosa, and it is exceedingly rare in the tongue. Herein, we present a case of PSCC in an 85-year-old male with a history of heart transplant and long-term use of immunosuppression medication. A verrucous pedunculated mass measuring 3.5 cm in the greatest dimension was present on the tip of tongue and a partial glossectomy was performed. Histological diagnosis was well differentiated PSCC with focal and minimal stalk invasion. No vascular nor perineural invasion was identified. Based on the current WHO and AJCC oral cancer staging system, the tumor stage was T2N0M0. The tumor cells were focally positive for p16, but in situ hybridization was negative for low-risk HPV (types 6 and 11) and high-risk HPV (types 16, 18, 31, 33 and 51). To the best of our knowledge, this is the first documented case of PSCC present on the tip of tongue in patients with long-term immune suppression. The pathogenesis, stage and prognosis of this entity are discussed. More case studies with long-term follow up are needed to achieve an accurate tumor stage and definite prognosis.

Cystic squamous cell carcinoma (SCC) of the lateral neck is considered metastatic human papilloma-virus (HPV)-related oropharyngeal SCC (HPV-OPSCC) until proven otherwise. P16 immunohistochemistry is diffusely positive in those carcinomas and is used as a surrogate marker of active human papillomavirus (HPV) infection. Thyroglossal duct cysts (TDC) are one of the differential diagnoses for cystic neck lesions. SCC arising from TDC is extremely rare. In this study, we report a p16-positive cystic SCC located in the midline neck. Radiologic features and the presence of thyroid tissue in the cyst wall indicated that it was a TDC. The morphologic features of the lesion raised the question: is the carcinoma metastatic HPV-OPSCC? The HPV confirmative test, high-risk HPV RNA in situ hybridization, was negative. We then studied p16 immunohistochemistry in the squamous epithelium of benign TDC and found that rare benign TDC can show diffuse and strong p16 positivity.