Abstract
BackgroundLower prevalence HPV infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. We therefore evaluated the characteristic and association of p16 and HPV in Thai patients with HNSCC.MethodsWe used immunohistochemistry and qPCR, respectively, to detect p16 and HPV DNA in archrival formalin-fixed paraffin-embedded HNSCC tissues. Patient characteristics and survival were analyzed.Resultsp16 expression was detected in tumors of 72 of 662 (10.9%) patients with HNSCC and was significantly associated with higher-grade histology, advanced nodal stage, and oropharynx. p16 was expressed in 28 and 6.5% of patients with OPSCC or non-OPSCC, respectively, and HPV DNA was detected in 15.6 and 1% of patients, respectively. Using p16 as a surrogate for HPV status, sensitivities were 80 and 25% in OPSCC and non-OPSCC, respectively. Positive and negative predictive rates of OPSCC were 38 and 95%. Discordance rates between HPV and p16 were 23 and 7% in OPSCC and non-OPSCC, respectively. Overall survival (OS) were significantly longer in both p16-positive OPSCC (p = 0.049), and non-OPSCC (p = 0.003).ConclusionsLow prevalence of p16 and HPV associated OPSCC and non-OPSCC were confirmed in Thai patients. High discordance and low positive predictive rates of p16 were observed in HPV-associated OPSCC. p16 was a significant prognostic factor for OS for patients with OPSCC or non-OPSCC. Therefore, HPV testing should be performed to assess the association of HPV with HNSCC regardless of p16 expression.
Highlights
Lower prevalence Human papilloma virus (HPV) infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC
The baseline characteristics of p16-positive and p16-negative patients were comparable, except for the site of primary tumor, histological grade, and lymph node (LN) stage at diagnosis (Table 1). p16 expression was significantly associated with higher-grade histology (p < 0.001) and advanced LN stage (p = 0.049)
The oropharynx was the primary site of tumors that were significantly associated with p16 expression (p < 0.001)
Summary
Lower prevalence HPV infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. P16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. We evaluated the characteristic and association of p16 and HPV in Thai patients with HNSCC. HPV infection induces many alterations in the CDK4Cyclin D-Rb and apoptotic pathways such as upregulation of the expression of the cyclin dependent kinase inhibitor 2A (p16) as well as loss of retinoblastoma (Rb) and tumor suppressor protein p53 functions [2,3,4]. The HPV E6 protein forms a complex with the E3 ubiquitin ligase E6-associated protein (E6AP), and ubiquitinates the p53 tumor suppressor protein. The HPV E7 protein binds to the cullin-2 ubiquitin ligase complex and ubiquitinates phosphorylated Rb (pRb), resulting in deregulation of the G1/S phase of the cell cycle. In the absence of pRb function, the E2F family of transcription factors is released and S-phase genes are transcribed, leading to cell proliferation and increased expression of p16 [5]
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