The signature of a T-cell response to KSHV persists across space and time in individuals with epidemic and endemic KS from Uganda.

Inadequate T-cell control of Kaposi sarcoma-associated herpesvirus (KSHV) infection predisposes to development of Kaposi sarcoma (KS), but little is known about the T-cell response to KSHV. Postulating that KS tumors contain abundant KSHV-specific T-cells, we performed transcriptional profiling and T-cell receptor (TCR) repertoire analysis of tumor biopsies from 144 Ugandan adults with KS. We show that CD8+ T-cells and M2-polarized macrophages dominate the tumor micro-environment (TME). The TCR repertoire of KS tumor infiltrating lymphocytes (TIL) is shared across non-contiguous tumors and persists across time. Clusters of T-cells with predicted shared specificity for uncharacterized antigens, potentially encoded by KSHV, comprise ~25% of KS TIL, and are shared across tumors from different time points and individuals. Single-cell RNA-sequencing of blood identifies a non-proliferating effector memory phenotype and captured the TCRs in 14,698 putative KSHV-specific T-cells. These results suggest that a polyspecific KSHV-specific T-cell response inhibited by M2 macrophages exists within the KS TME, and provide a foundation for studies to define its specificity at a large scale.

A prospective study of clinical outcomes of HIV-associated and HIV-negative Kaposi sarcoma in Uganda.

OBJECTIVE: Improved understanding of the effect of HIV infection on Kaposi sarcoma (KS) presentation and outcomes will guide development of more effective KS staging and therapeutic approaches. We enrolled a prospective cohort of epidemic (HIV-positive; HIV + KS) and endemic (HIV-negative; HIV - KS) KS patients in Uganda to identify factors associated with survival and response. METHODS: Adults with newly diagnosed KS presenting for care at the Uganda Cancer Institute (UCI) in Kampala, Uganda, between October 2012 and December 2019 were evaluated. Participants received chemotherapy per standard guidelines and were followed over 1 year to assess overall survival (OS) and treatment response. RESULTS: Two hundred participants were enrolled; 166 (83%) had HIV + KS, and 176 (88%) were poor-risk tumor (T1) stage. One-year OS was 64% (95% confidence interval [CI] 57-71%), with the hazard of death nearly threefold higher for HIV + KS (hazard ratio [HR] = 2.93; P  = 0.023). Among HIV + KS, abnormal chest X-ray (HR = 2.81; P  = 0.007), lower CD4 + T-cell count (HR = 0.68 per 100 cells/µl; P  = 0.027), higher HIV viral load (HR = 2.22 per log 10  copies/ml; P  = 0.026), and higher plasma Kaposi sarcoma-associated herpesvirus (KSHV) copy number (HR = 1.79 per log 10  copies/ml; P  = 0.028) were associated with increased mortality. Among HIV - KS, factors associated with mortality included Karnofsky score <70 (HR = 9.17; P  = 0.045), abnormal chest X-ray (HR = 8.41; P  = 0.025), and higher plasma KSHV copy number (HR = 6.21 per log 10  copies/ml; P  < 0.001). CONCLUSIONS: Although survival rates were better for HIV - KS than HIV + KS, the high mortality rate seen in both groups underscores the urgent need to identify new staging and therapeutic approaches. Factors associated with mortality, including high plasma KSHV, may serve as important targets of therapy.

Capacity building for cancer prevention and early detection in the Ugandan primary healthcare facilities: Working toward reducing the unmet needs of cancer control services.

BACKGROUND: In 2018, approximately 60,000 Ugandans were estimated to be suffering from cancer. It was also reported that only 5% of cancer patients access cancer care and 77% present with late-stage cancer coupled with low level of cancer health literacy in the population despite a wide coverage of primary healthcare facilities in Uganda. We aimed to contribute to reducing the unmet needs of cancer prevention and early detection services in Uganda through capacity building. METHODS: In 2017, we conducted two national and six regional cancer control stakeholders' consultative meetings. In 2017 and 2018, we trained district primary healthcare teams on cancer prevention and early detection. We also developed cancer information materials for health workers and communities and conducted a follow-up after the training. RESULTS: A total of 488 primary healthcare workers from 118 districts were trained. Forty-six health workers in the pilot East-central subregion were further trained in cervical, breast, and prostate cancer early detection (screening and early diagnosis) techniques. A total of 32,800 cancer information, education and communication materials; breast, cervical, prostate childhood and general cancer information booklets; health education guide, community cancer information flipcharts for village health teams and referral guidelines for suspected cancer were developed and distributed to 122 districts. Also, 16 public and private-not-for-profit regional hospitals, and one training institution received these materials. Audiovisual clips on breast, cervical, and prostate cancer were developed for mass and social media dissemination. A follow-up after six months to one year indicated that 75% of the districts had implemented at least one of the agreed actions proposed during the training. CONCLUSIONS: In Uganda, the unmet needs for cancer control services are enormous. However, building the capacity of primary healthcare workers to integrate prevention and early detection of cancer into primary health care based on low-cost options for low-income countries could contribute to reducing the unmet needs of cancer prevention and early detection in Uganda.

Mobile cancer prevention and early detection outreach in Uganda: Partnering with communities toward bridging the cancer health disparities through "asset-based community development model".

BACKGROUND: Communities in low-income countries are characterized by limited access to cancer prevention and early detection services, even for the commonest types of cancer. Limited resources for cancer control are one of the contributors to cancer health disparities. We explored the feasibility and benefit of conducting outreaches in partnership with local communities using the "asset-based community development (ABCD)" model. METHODS: We analyzed the quarterly Uganda cancer institute (UCI) community outreach cancer health education and screening output reported secondary data without individual identifiers from July 2016 to June 2019 to compare the UCI-hospital-based and community outreach cancer awareness and screening services based on the ABCD model. RESULTS: From July 2016 to June 2019, we worked with 107 local partners and conducted 151 outreaches. Of the total number of people who attended cancer health education sessions, 201 568 (77.9%) were reached through outreaches. Ninety-two (95%) cancer awareness TVs and radio talk-shows conducted were sponsored by local partners. Of the total people screened; 22 795 (63.0%) cervical, 22 014 (64.4%) breast, and 4904 (38.7%) prostate screening were reached through community outreach model. The screen-positive rates were higher in hospital-based screening except for Prostate screening; cervical, 8.8%, breast, 8.4%, prostate, 7.1% than in outreaches; cervical, 3.2%, breast, 2.2%, prostate, 8.2%. Of the screened positive clients who were eligible for precancer treatment like cryotherapy for treatment of precervical cancer lesions, thousands-folds monetary value and productive life saved relative to the market cost of cancer treatment and survival rate in Uganda. When the total number of clients screened for cervical, breast, and prostate cancer are subjected to the incremental cost of specific screening, a greater portion (98.7%) of the outreach cost was absorbed through community partnership. CONCLUSIONS: Outreaching and working in collaboration with communities as partners through asset-based community development model are feasible and help in cost-sharing and leverage for scarce resources to promote primary prevention and early detection of cancer. This could contribute to bridging the cancer health disparities in the target populations.

Evaluation of a Predictive Staging Model for HIV-Associated Kaposi Sarcoma in Uganda.

BACKGROUND: HIV-associated Kaposi sarcoma (KS) is commonly staged using the AIDS Clinical Trials Group criteria, which classify 3 variables- tumor extent (T), immune status (I), and systemic symptoms (S)-into good risk (0) and poor risk (1). Although validated in the United States and Europe, these criteria have not been systematically evaluated in sub-Saharan Africa, where the burden of KS is greatest. METHODS: We reviewed medical charts of adult patients with HIV-associated KS seen at the Uganda Cancer Institute from 1992 to 2007. Vital status at 2 years after KS diagnosis was determined from the medical chart, or by contacting the patient or next of kin. Survival estimates used Kaplan-Meier methods. Predictors were evaluated for 2 periods: 0-4 months and 4-24 months after diagnosis. RESULTS: At 2 years after diagnosis, 167 (41%) patients were alive, 156 (39%) had died, and 81 (20%) were lost to follow-up. The Kaplan-Meier estimate of 2-year survival was 57%. S1 was associated with death in months 0-4 [hazard ratio: 6.4, 95% confidence interval: 1.9-21.1], whereas T1 was associated with death in months 4-24 [hazard ratio: 4.0, 95% confidence interval: 1.4 to 11.5]. Immune status was not associated with survival. CONCLUSIONS: Systemic symptoms were strongly associated with death in the early period after KS diagnosis, whereas tumor status was most predictive of death in the 4- to 24-month period. These findings suggest that different processes may influence outcomes in early and late periods following KS diagnosis. Further studies are needed to confirm these observations and to identify better predictors of KS survival in sub-Saharan Africa.

United against cancer: prevention to end-of-life care-highlights from the Uganda Cancer Institute-Palliative Care Association of Uganda Joint International Conference on Cancer and Palliative Care and the 7th Palliative Care Conference, 24-25 August 2017, Kampala, Uganda.

The Uganda Cancer Institute (UCI) and the Palliative Care Association of Uganda (PCAU) jointly hosted an international conference on cancer and palliative care in August 2017 in Kampala, Uganda. At the heart of the conference rested a common commitment to see patient care improved across Uganda and the region. The theme - United Against Cancer: Prevention to End-of-Life Care - reflected this joint vision and the drive to remember that cancer care should include prevention, early diagnosis and screening, treatment, rehabilitation and palliative care. The conference brought together 451 delegates from 17 countries. The key themes of the conference included: the importance of the World Health Assembly Resolutions on Palliative Care (2014) and cancer care (2017); the need to develop a National Cancer Control Programme; strategies for effective cancer diagnosis and treatment in low- and middle-income countries; advocacy, human rights and access to essential medicines, including access to opioids and nurse prescribing; paediatric care; leadership and commitment; collaboration; resources (financial and human), the recognition that palliative care is not limited to cancer care and the importance of learning from each other. The conference also gave the opportunity to celebrate the 50th Anniversary of the UCI, with a celebration dinner attended by the Minister of Health and the US Ambassador. Participants reported that the conference was a forum that updated them in all aspects of cancer and palliative care, which challenged their knowledge, and was enlightening in terms of current treatment options for individuals with cancer. The benefits of having a joint conference were recognised, allowing for further networking between cancer and palliative care organisations. This conference, highlighting many developments in cancer and palliative care, served as a unique opportunity to bring people together and unite them in developing cancer and palliative care.