title: HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer.
abstract: OBJECTIVE
  As HPV-induced cases of oral malignancy increase, it is important to understand the molecular differences between HPV positive and negative head and neck squamous cell carcinoma (HNSCC). PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs aberrantly expressed in cancer. We analyzed global piRNA expression patterns to define the HNSCC piRNA transcriptome and assess whether HPV infection status associates with changes in piRNA levels.
  
  
  METHODS
  A total of 498 HNSCC small RNA sequencing libraries were acquired from the Cancer Genomics Hub (cgHUB) Data Repository and a custom sequence analysis pipeline was developed to deduce piRNA expression from raw sequencing data. Expression matrices were aligned to clinicopathological features in order to analyze piRNA expression patterns across different HNSCC groups. The association of a piRNA signature with HPV-positive patient survival was evaluated using a Cox proportional hazard model.
  
  
  RESULTS
  Analysis of piRNA levels between HNSCC and non-malignant tissues revealed distinct expression patterns, with 87 piRNAs exclusively expressed in tumor samples. HPV infection status affected the expression of 41 of these piRNAs. Eleven (26.8%) piRNAs were significantly downregulated in HPV16/18 tumors compared to other HPV types. Remarkably, expression of a combination of five-piRNAs in HPV-positive HNSCC tumors was associated with worse overall survival.
  
  
  CONCLUSIONS
  The expression of specific piRNAs is deregulated in HNSCC, and changes with both HPV status and type. Importantly, a five-piRNA signature is able to delineate a subset of HPV-positive HNSCC patients with poor outcome, highlighting the potential utility of piRNAs in patient management.
authors: Natalie
authors: N
authors: Firmino
authors: Victor D
authors: VD
authors: Martinez
authors: David A
authors: DA
authors: Rowbotham
authors: Katey S S
authors: KSS
authors: Enfield
authors: Kevin L
authors: KL
authors: Bennewith
authors: Wan L
authors: WL
authors: Lam
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D006801:Humans; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D034741:RNA, Small Interfering
keywords: Head and Neck cancer; Human papillomavirus; Kiwi-interacting RNAs; Non-coding RNA; Survival; piRNA