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.

世界卫生组织承认人乳头瘤病毒 (HPV) 是多种癌症的病因，包括头颈癌。 HPV是一种双链DNA病毒，感染后可以通过细胞和病毒启动子控制其病毒基因表达。在癌细胞中，HPV 基因组被检测为整合到宿主基因组中、游离型（染色体外）或整合型和游离型的混合物。病毒整合需要病毒和宿主DNA的断裂，整合率与DNA损伤的程度相关。有趣的是，HPV 阳性头颈癌患者通常预后良好，但一组 HPV 完全整合的患者表现出最差的临床结果。这些患者的病毒基因表达降低，细胞毒性 T 细胞浸润有限。临床上有效治疗应用的一个障碍是仅检测 HPV 阳性而不考虑 HPV 整合状态。这篇综述将讨论 HPV 整合作为头颈癌治疗反应的潜在决定因素，并向该领域强调一种可以减轻癌症负担并提高患者生存率的新治疗途径。