Human Papillomavirus Genome Integration and Head and Neck Cancer

Abstract

We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

Accurate Detection of HPV Integration Sites in Cervical Cancer Samples Using the Nanopore MinION Sequencer Without Error Correction

“…Our data indicated that most of the integration sites exist in the intergenic region of the human genome, concordant with previous studies ( Bodelon et al, 2016 ; Pinatti et al, 2017 ; Brant et al, 2018 ; Koneva et al, 2018 ; Li et al, 2019 ). Since human genome was identified with large portion (∼60%) of intergenic region, our results identified about 40% integration sites located in intergenic region of human genome, which showed no significant difference.…”

The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue

“…The largest number of integrated forms was in stage III and IV [ 6 ]. Detection of HPV in its integrated form has also been reported in several other cancers [ 30 , 42 , 43 ]. The integration of HPV genome leads to changes in the expression of viral oncogenes (E6 and E7), dysregulating of critical cell cycle checkpoints, increased genetic instability in the host and finally tumour development [ 44 ].…”

Controlled Drug Delivery Systems for Oral Cancer Treatment—Current Status and Future Perspectives

“…The HPV diagnosis is critical in planning treatment for oropharyngeal cancer (OPC) patients [23,24,25]. Within OPC, there is a marked difference between clinical behaviors and outcomes for patients who test positive versus negative for HPV infection.…”