Abstract
Background: Increasing evidence indicates an etiological role of human papillomavirus (HPV) in head and neck cancers, particularly oropharyngeal squamous cell carcinoma (OPSCC). However, the association between HPV and other cancers, including esophageal and tongue remains unclear.
Methods: We compared the molecular characteristics of HPV18 E6 and E7 in esophageal (EC109 and EC9706) and tongue (Tca83) cancer cell lines with reference to cervical cancer (HeLa). We studied the expression of HPV transcripts using Next Generation RNA sequencing. We used small interference RNA (siRNA) against HPV18 oncoproteins to verify their oncogenic roles in molecular signaling, targeting metalloproteases and apoptotic pathways in these cancers.
Results: We observed that the HPV transcription profiles of esophageal and tongue cancer cells mimicked that of cervical cancer cells, with notable disruption of E2, and expression of E6, spliced E6 (E6 * ), E7, E1 and L1 transcripts. As with cervical cancer cells, p53 and its downstream transactivation target, p21, were found to be the major targets of E6 in esophageal and tongue cancer cell lines. Intriguingly, E7 preferentially targeted p130 in the two esophageal cancer cell lines, instead of pRb as in cervical cancer. Tca83 exhibited an E7 to E6 transcript ratio comparable to HeLa (cervix), targeted the ERK1/2 and MMP2 pathways, and was dependent on E6 and E7 to survive and proliferate. In contrast, both the esophageal cancer cell lines were distinct from HeLa in these aspects.
Conclusion: This is the first study to delineate the transcripts expression and role of HPV18 E6 and E7 in esophageal and tongue cancer cell lines. This findings suggest that HPV18 plays an oncogenic role in inducing these cancers, albeit via distinct pathways than those observed in cervical cancer.