Background: Anal squamous cell carcinoma (SCC) is a rare gastrointestinal malignancy with rising incidence, both in the United States and internationally. The primary risk factor for anal SCC is human papillomavirus (HPV) infection. However, there is a growing burden of disease in patients with human immunodeficiency virus (HIV) and HPV coinfection, with the incidence of anal SCC significantly increasing in this population. This is particularly true in HIV-infected men. The epidemiologic correlation between HIV-HPV coinfection and anal SCC is established; however, the immunologic mechanisms underlying this relationship are not well understood. Summary: HIV-related immunosuppression due to low circulating CD4+ T cells is one component of increased risk, but other mechanisms, such as the effect of HIV on CD8+ T lymphocyte tumor infiltration and the PD-1/PD-L1 axis in antitumor and antiviral response, is emerging as significant contributors. The goal of this article is to review existing research on HIV-HPV coinfected anal SCC and precancerous lesions, propose explanations for the detrimental synergy of HIV and HPV on the pathogenesis and immunologic response to HPV-associated cancers, and discuss implications for future treatments and immunotherapies in HIV-positive patients with HPV-mediated anal SCC. Key Messages: The incidence of anal squamous cell carcinoma is increased in human immunodeficiency virus (HIV)-infected patients, even in patients on highly active antiretroviral therapy. Locoregional HIV infection may enhance human papillomavirus oncogenicity. Chronic inflammation due to HIV infection may contribute to CD8+ T lymphocyte exhaustion by upregulating PD-1 expression, thereby blunting cytotoxic antitumor response.
Pathobiology

中文翻译：

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人类免疫缺陷病毒感染促进人乳头瘤病毒介导的肛门鳞状细胞癌发生：免疫学和病理生物学综述

背景：肛门鳞状细胞癌 (SCC) 是一种罕见的胃肠道恶性肿瘤，其发病率在美国和国际上均呈上升趋势。肛门 SCC 的主要危险因素是人乳头瘤病毒 (HPV) 感染。然而，人类免疫缺陷病毒 (HIV) 和 HPV 合并感染患者的疾病负担越来越重，该人群中肛门 SCC 的发病率显着增加。在感染 HIV 的男性中尤其如此。建立了 HIV-HPV 合并感染与肛门 SCC 之间的流行病学相关性；然而，这种关系背后的免疫机制尚不清楚。概括：由于循环 CD4+ T 细胞低导致的 HIV 相关免疫抑制是风险增加的一个组成部分，但其他机制，例如 HIV 对 CD8+ T 淋巴细胞肿瘤浸润和 PD-1/PD-L1 轴在抗肿瘤和抗病毒反应中的影响，正在成为重要的贡献者。本文的目的是回顾现有的关于 HIV-HPV 共感染肛门 SCC 和癌前病变的研究，就 HIV 和 HPV 对 HPV 相关癌症的发病机制和免疫反应的有害协同作用提出解释，并讨论对未来治疗和HPV 介导的肛门 SCC 的 HIV 阳性患者的免疫疗法。关键信息：人类免疫缺陷病毒 (HIV) 感染患者的肛门鳞状细胞癌发病率增加，即使在接受高效抗逆转录病毒治疗的患者中也是如此。局部区域性 HIV 感染可能会增强人乳头瘤病毒的致癌性。HIV感染引起的慢性炎症可能通过上调PD-1表达导致CD8+ T淋巴细胞耗竭，从而减弱细胞毒性抗肿瘤反应。
病理学