Abstract
The aim of the present study is to determine the expression levels of PYHIN (IFI16 and AIM2) and APOBEC3 (A3A, A3B, A3C, A3D, A3F, A3G, and A3H) gene family members in a cohort of patients with head and neck squamous cell carcinoma (HNSCC) and assess their potential correlation with human papillomavirus (HPV) infection status, clinical characteristics, and survival. For this purpose, 34 HNSCC tissue specimens along with healthy surrounding mucosa were collected from patients surgically treated for HNSCC. Nucleic acids were isolated to assess the presence of HPV and the expression levels of selected molecular markers. Survival analysis was carried out using the Kaplan-Meier method. In HPV-negative (HPV-) HNSCCs, we detected low mRNA expression levels of IFI16, A3A, and A3B, whereas these genes were upregulated of 2-100 folds in HPV-positive (HPV+) tumors (p < 0.05). Interestingly, AIM2 gene expression levels were predominantly unchanged in HPV+ HNSCCs compared to their HPV- counterparts, in which AIM2 was predominantly upregulated (10% vs. 50% of patients). In HPV- tumors, upregulation of TP53, NOTCH1, PD-L1, and IFI16 correlated with lower occurrence of nodal metastases. On the other hand, the expression of APOBEC family members did not correlate with clinical characteristics. Regarding survival, patients with upregulated A3F gene expression had a worse prognosis, while patients without changes in A3H expression had a lower survival rate. In conclusion, our findings indicate that the innate immune sensors IFI16 and AIM2 and some APOBEC family members could be potentially used as biomarkers for disease outcome in HNSCC patients regardless of HPV presence.
Highlights
Head and neck cancer is the sixth most common type of cancer and represents about6% of all cases of tumors worldwide
Human papillomavirus (HPV) positivity correlated with an increasing incidence rate of oropharyngeal cancers in men younger than age 50 without a history of tobacco use, with HPV type 16 (HPV16) being the most commonly found high risk HPV in these head and neck squamous cell carcinoma (HNSCC) [2]
One hundred patients surgically treated for HNSCC between January 2012 and September 2018 at Otorhinolaryngology Division of the University of Turin were enrolled in this study and evaluated for the presence of HPV
Summary
Head and neck cancer is the sixth most common type of cancer and represents about6% of all cases of tumors worldwide. 90% of all head and neck tumors, which arise predominantly in the mucosa of the oral cavity, pharynx, and larynx, are histologically classified as squamous cell carcinomas (HNSCCs). Human papillomavirus (HPV), alongside other risk factors such as alcohol and tobacco consumption, is emerging as an important etiological factor of HNSCC. In this regard, HPV positivity correlated with an increasing incidence rate of oropharyngeal cancers in men younger than age 50 without a history of tobacco use, with HPV type 16 (HPV16) being the most commonly found high risk HPV in these HNSCCs [2]. High-risk HPV types have been detected in 45-70% of oropharyngeal cancers [3]. Despite significant progress in HNSCC disease management, the prognosis of recurrent HNSCCs still remains poor in most cases [5]
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