Emerging roles of PIWI-interacting RNAs (piRNAs) and PIWI proteins in head and neck cancer and their potential clinical implications.

Head and neck squamous cell carcinoma (HNSCC) are among the well-known neoplasms originating in the oral cavity, pharynx, and larynx. Despite advancements in chemotherapy, radiotherapy, and surgery, the survival rates of the patients are low, which has posed a major therapeutic challenge. A growing number of non-coding RNAs (ncRNAs), for instance, microRNAs, have been identified whose abnormal expression patterns have been implicated in HNSCC. However, more recently, several seminal research has shown that piwi-interacting RNAs (piRNAs), a promising and young class of small ncRNA, are linked to the emergence and progression of cancer. They can regulate transposable elements (TE) and gene expression through multiple mechanisms, making them potentially more powerful regulators than miRNAs. Hence, they can be more promising ncRNAs candidates for cancer therapeutic intervention. Here, we surveyed the roles and clinical implications of piRNAs and their PIWI proteins partners in tumorigenesis and associated molecular processes of cancer, with a particular focus on HNSCC, to offer a new avenue for diagnosis, prognosis, and therapeutic interventions for the malignancy, improving patient's outcomes.