PYHIN genes as potential biomarkers for prognosis of human papillomavirus-positive or -negative head and neck squamous cell carcinomas

  • Giuseppe Riva
  • Giancarlo Pecorari
  • Matteo Biolatti
  • Sara Pautasso
  • Irene Lo Cigno
  • Massimiliano Garzaro
  • Valentina Dell’Oste
  • Santo LandolfoEmail author
Original Article


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.


Head and neck cancer Human papillomavirus PYHIN proteins APOBEC proteins Survival 



This work was supported by: Italian Ministry of Education, University and Research-MIUR (PRIN 2015 to VDO, 2015RMNSTA); Research Funding from the University of Turin (DELV_RILO_17_01, LANS_RILO_17_01, 2018, to SL and VDO). The funding agencies had no role in study design, data collection and interpretation, as well as in the decision to submit this work for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Public Health and Pediatric SciencesUniversity of TurinTurinItaly
  2. 2.Otorhinolaryngology Division, Department of Surgical SciencesUniversity of TurinTurinItaly
  3. 3.Department of Translational MedicineUniversity of Eastern Piedmont “A. Avogadro”NovaraItaly
  4. 4.Otorhinolaryngology Division, Department of SurgeryUniversity of Eastern Piedmont “A. Avogadro”NovaraItaly

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