Abstract
Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.
Highlights
Tonsillar squamous cell carcinoma (TSCC) is the most common type of oropharyngeal cancer, accounting for approximately 70–80% of all cancers of this anatomical region, representing a highly aggressive malignancy with early lymphatic dissemination [1, 2]
While homeodomain-interacting protein kinase 2 (HIPK2) overexpression was observed in 57% of TSCC cases, its expression was significantly decreased in the normal tonsillar mucosa (27.8%, 5/18)
HIPK2 overexpression was associated with poorly differentiated tonsil cancer, which is an unfavorable histological factor in patients with TSCC
Summary
Tonsillar squamous cell carcinoma (TSCC) is the most common type of oropharyngeal cancer, accounting for approximately 70–80% of all cancers of this anatomical region, representing a highly aggressive malignancy with early lymphatic dissemination [1, 2]. The incidence rate of TSCC has significantly increased from 0.35 to 1.5 cases per 100,000 individuals in the last three decades worldwide, especially amongst men and those aged 40–59 years [3]. Human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinomas (SCCs) have become an important subgroup of head and neck SCCs, and the tonsillar region is the most common location for HPV-associated head and neck SCCs. HPV-associated oropharyngeal SCCs are associated with an improved response to radiochemotherapy and have a better prognosis than HPV-negative tumors [6,7,8]. Several studies have shown that homeodomain-interacting protein kinase 2 (HIPK2) is an important tumor suppressor involved in BioMed Research International
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