Impact of immune reconstitution on outcomes to chemoradiation in cervical cancer

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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.