Navigating therapeutic strategies: HPV classification in head and neck cancer

Abstract

The World Health Organisation recognised human papillomavirus (HPV) as the cause of multiple cancers, including head and neck cancers. HPV is a double-stranded DNA virus, and its viral gene expression can be controlled after infection by cellular and viral promoters. In cancer cells, the HPV genome is detected as either integrated into the host genome, episomal (extrachromosomal), or a mixture of integrated and episomal. Viral integration requires the breakage of both viral and host DNA, and the integration rate correlates with the level of DNA damage. Interestingly, patients with HPV-positive head and neck cancers generally have a good prognosis except for a group of patients with fully integrated HPV who show worst clinical outcomes. Those patients present with lowered expression of viral genes and limited infiltration of cytotoxic T cells. An impediment to effective therapy applications in the clinic is the sole testing for HPV positivity without considering the HPV integration status. This review will discuss HPV integration as a potential determinant of response to therapies in head and neck cancers and highlight to the field a novel therapeutic avenue that would reduce the cancer burden and improve patient survival.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients

“…This approach helped to identify the presence of a subset of HPV-positive cells with undetectable HPV expression (E6 and E7 oncoproteins), termed HPV-off and characterized by a phenotype of decreased proliferation and increased senescence, which are associated with decreased response to treatment, increased invasiveness, and poor prognosis, which could be attributed in part to augmented integration events. These findings suggest the existence of a group of HPV-positive malignant cells that lose an active transcriptional state, resulting in the suppression of hyperproliferative features, which ultimately confers resistance to conventional treatments for HPV-positive HNSCC tumors [68].…”

Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status

“…Up to 96% of these tumors are HPV16-positive (HPV16+) and, in contrast to cervical cancer, precancerous lesions are hardly detected [ 6 ]. HPV+ HNSCCs seem to differ from HPV-negative (HPV−) ones in genetic, epigenetic, and protein expression profiles, as well as epidemiological factors and clinical characteristics [ 7 , 8 , 9 , 10 ], but the currently available treatments for both groups are almost the same [ 7 , 11 , 12 ]. Similar to cervical infections, the majority of head and neck HPV infections (as high as 80%) are cleared by the immune system in healthy individuals within 6 to 20 months of the initial infection [ 3 , 13 ].…”

“…HPV, a double-stranded circular DNA virus, greatly contributes to various cancer types [ 10 , 16 , 17 , 18 , 19 ]. Over 450 HPV genomes have been sequenced and categorized into five genera [ 20 , 21 ].…”