Impact of immune reconstitution on outcomes to chemoradiation in cervical cancer

宫颈癌是发展中国家妇女癌症的主要原因，在艾滋病毒(人类免疫缺陷病毒)的背景下，它是艾滋病的定义疾病。在博茨瓦纳，大约17%的人口艾滋病毒阳性，大约60%-80%的宫颈癌患者伴有艾滋病毒感染。在南部非洲，就像在资源匮乏的情况下一样，妇女在侵袭性宫颈癌发作后的存活率除了艾滋病毒状况外，还受到不理想的诊断、治疗反应和后续行动的不利影响。该项目的长期目标是通过确定与侵袭性宫颈癌治疗反应相关的临床参数(耐受性和毒性)和免疫学参数，提高接受化疗和放射治疗的HIV+妇女的存活率。这些研究的结果将被用来形成未来的多学科战略，以最大限度地治疗博茨瓦纳艾滋病毒阳性妇女与人类乳头瘤病毒(HPV)相关的宫颈癌。与HIV感染相关的免疫抑制已被确定为多种恶性肿瘤的危险因素，包括非霍奇金淋巴瘤、卡波西肉瘤、默克尔细胞癌、宫颈癌和肺癌。比较研究表明，艾滋病毒患者癌症增加的模式与免疫抑制的移植患者相似，艾滋病毒患者的风险与CD4+T淋巴细胞计数有关，这表明免疫缺陷可能是艾滋病毒患者恶性肿瘤增加的根本原因。在HIV阳性的宫颈癌妇女中，前瞻性的临床结果研究有限，回顾研究表明，由于不明原因，生存率较低，对化疗和放射治疗的耐受性降低。因此，在我们对HIV感染和抗逆转录病毒疗法(ART)对耐受性的影响以及免疫重建对宫颈癌治疗反应的贡献的理解上存在差距，因为这些研究都没有研究ART对化疗和放射治疗的影响，或者免疫状态如何影响结果。我们的建议将解决接受HPV相关性浸润性宫颈癌化疗的HIV+妇女的ART后免疫重建与癌症治疗结果之间的关系。这一信息将影响临床实践或治疗剂量，因为ART或免疫重建的存在目前并不被认为是HPV相关宫颈癌治疗反应的决定因素。

Cervical cancer is the leading cause of cancer in women living in the developing world, and in the setting of HIV (human immunodeficiency virus), it is an AIDS defining illness. In Botswana, approximately 17% of the population is HIV positive and approximately 60%-80% of cervical cancer patients have concomitant HIV infection. In Southern Africa as in resource-poor settings, women's survival after the onset of invasive cervical cancer is adversely affected by suboptimal diagnosis, treatment response, and follow-up in addition to HIV status. The long-range goals of this project are to improve survival in HIV+ women undergoing chemo-radiotherapy by defining the clinical (tolerability and toxicity) and immunological parameters associated with invasive cervical cancer therapy response. The results of these studies will be used to shape future multi-disciplinary strategies to maximize treatment of HIV positive women with human papillomavirus (HPV) -associated cervical cancer in Botswana. Immunosuppression associated with HIV infection has been established as a risk factor for a variety of malignancies, including non-Hodgkin lymphoma, Kaposi Sarcoma, Merkel cell carcinoma, cervical cancer, and lung cancer. Comparative studies have shown that the pattern of increased cancers in HIV patients was similar to that observed in immunosuppresed transplant patients and that the risk in HIV patients correlates with CD4+ T-lymphocyte count, suggesting that immunodeficiency is likely the underlying cause of increased malignancy observed in HIV patients. Amongst women who are HIV positive with cervical cancer, prospective clinical outcome studies are limited and retrospective studies have demonstrated inferior survival and decreased tolerability to chemo-radiotherapy for unclear reasons. Therefore,' a gap exists in our understanding of the impact of HIV infection and anti-retroviral therapy (ART) on tolerability and the contribution of immune reconstitution on cervical cancer treatment response as none of these studies have yet examined the impact of ART on chemoradiotherapy or how immunologic status affects outcomes. Our proposal will address the relationship between immune reconstitution following ART and cancer therapy outcomes in HIV+ women receiving chemoradiotherapy for HPV-associated invasive cervical carcinoma. This information will impact clinical practice or therapy dosing as the presence of ART or immune reconstitution is not currently considered as a determinant to HPV-associated cervical cancer treatment response.