The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing, with UV radiation being the main cause. Other risk factors are age, sex, skin type and immunosuppression. Human papillomaviruses (HPVs) are associated with benign and malignant skin tumours. In contrast to anogenital and oropharyngeal carcinomas, which are caused by alpha papillomaviruses, the HPV types associated with cSCC belong to the beta-HPV genus. These viruses infect the skin epithelium and are widespread in skin samples from healthy people. It is assumed that HPV amplifies the DNA damage caused by UV radiation and disrupts the repair mechanisms of the cells, without remaining permanently detectable in the tumour tissue, the so-called hit-and-run theory. The HPV status of tumours appears to have a positive influence on prognosis and response to therapy due to increased immune infiltration, in particular by tissue-resident memory T cells and activation of immune effector cells. This favours responses to immunotherapies such as PD-1/PD-L1 inhibitors, whereas immunosuppression may promote a pro-carcinogenic effect. In conclusion, the role of beta HPV in the development of cSCC appears to be closely associated with the immune status of the host. Depending on the immune status, beta HPV can play either a protective or a tumour-promoting role, and in view of the increasing incidence of skin cancer worldwide, enhancing the immune response against virus-infected keratinocytes, e.g., through HPV vaccination, could represent a promising approach for the prevention and therapy of squamous cell carcinomas.
皮肤鳞状细胞癌（cSCC）的发病率正持续上升，紫外线辐射是其主要诱因。其他风险因素包括年龄、性别、皮肤类型及免疫抑制状态。人乳头瘤病毒（HPV）与多种良恶性皮肤肿瘤相关。与由α属乳头瘤病毒引起的肛门生殖器和口咽部癌不同，与cSCC相关的HPV类型属于β属。这类病毒可感染皮肤上皮细胞，在健康人群的皮肤样本中广泛存在。研究认为HPV能放大紫外线辐射造成的DNA损伤，并破坏细胞修复机制，而病毒本身不会在肿瘤组织中持续存在——即所谓"打了就跑"理论。由于肿瘤组织中免疫细胞（特别是组织驻留记忆T细胞）浸润增加及免疫效应细胞激活，HPV阳性状态似乎对患者预后和治疗反应产生积极影响。这种免疫特征有利于PD-1/PD-L1抑制剂等免疫疗法的响应，而免疫抑制状态则可能促进致癌进程。综上所述，β属HPV在cSCC发展中的作用与宿主的免疫状态密切相关：根据免疫状态差异，β属HPV既可发挥保护作用，也可能促进肿瘤发展。鉴于全球皮肤癌发病率持续攀升，通过HPV疫苗接种等方式增强针对病毒感染角质形成细胞的免疫应答，可能成为预防和治疗鳞状细胞癌的有效策略。
The Role of HPV in the Development of Cutaneous Squamous Cell Carcinoma—Friend or Foe?
肿瘤(癌症)患者之家