The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Comparison of human papillomavirus-based cervical cancer screening strategies in Tanzania among women with and without HIV.

Cervical cancer is the most common female cancer in Eastern Africa, and the World Health Organization (WHO) recommends human papillomavirus (HPV)-based screening as a key element to eliminate the disease. In this cross-sectional study from Tanzania, we compared nine HPV-based cervical cancer screening strategies, including HPV testing at standard cut-off; HPV testing at increased viral load cut-offs; HPV testing with partial/extended genotyping, and HPV testing with visual inspection with acetic acid (VIA). We pooled data collected during 2008 to 2009 and 2015 to 2017 from 6851 women aged 25 to 65. Cervical cytology samples were HPV tested with Hybrid Capture 2, and HPV positive samples were genotyped with INNO-LiPA Extra II. Human immunodeficiency virus (HIV) testing and VIA were done according to local standards. We calculated sensitivity, specificity, positive and negative predictive value of screening strategies, with high-grade cytological lesions as reference, separately for women with and without HIV. HPV testing at standard cut-off (1.0 relative light units [RLU]) had highest sensitivity (HIV+: 97.8%; HIV-: 91.5%), but moderate specificity (HIV+: 68.1%; HIV-: 85.7%). Increasing the cut-off for HPV positivity to higher viral loads (5.0/10.0 RLU) increased specificity (HIV+: 74.2%-76.5%; HIV-: 89.5%-91.2%), with modest sensitivity reductions (HIV+: 91.3%-95.7%; HIV-: 83.5%-87.8%). Limiting test positivity to HPV types 16/18/31/33/35/45/52/58 improved specificity while maintaining high sensitivity (HIV+: 90.2%; HIV-: 81.1%). Triage with VIA and/or partial genotyping for HPV16/18 or HPV16/18/45 had low sensitivities (≤65%). In conclusion, HPV testing alone, or HPV testing with extended genotyping or increased viral load cut-offs, may improve cervical cancer screening in Sub-Saharan Africa.

Knowledge on human papilloma virus and experience of getting positive results: a qualitative study among women in Kilimanjaro, Tanzania.

BACKGROUND: Human papilloma virus (HPV) is a sexually transmitted infection causing more than 80% of cervical cancers. WHO recommends using of sensitive screening methods like HPV-testing to timely prevent future morbidity and mortality from cervical cancer. Pilot studies have shown that HPV-testing is feasible and can be scaled in developing country like Tanzania. However, there is limited information on women understanding, reactions and psychological challenges following diagnosis of high risk HPV (HR-HPV). This study explored the knowledge of women on HPV and their experience after HPV positive results in Kilimanjaro, Tanzania. METHODS: The study was part of a larger study that assessed incidence and persistence of HR-HPV among women aged 18 years and above in Kilimanjaro. This was a cross sectional study conducted in Moshi municipal council among women who had HR-HPV positive results at enrollment. In-depth interviews were conducted with 13 randomly selected women who were attending for follow-up after enrollment. Interviews were conducted at the health facility and Atlas.ti.8 was used to analyze the data using thematic framework analysis. RESULTS: Women had knowledge on HPV infection but they had different reactions following receiving positive HPV results. Reaction toward the positive HPV results had two extremes; some women had psychological effect (hopeless, death sentence, having cancer, being shocked, failure to disclose and psychosexual effects) while others women explained positive results is good as they are identified earlier, will be followed up and it has made them plan to continue with cervical cancer screening in future. CONCLUSION: Women had knowledge on HPV, but positive results lead to negative and positive experiences by women. Clinicians and programs need to develop interventions and good strategies to minimize the psychological and social burden of testing positive for HPV.

An international report on bacterial communities in esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Comparative transcriptome analysis of endemic and epidemic Kaposi's sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis.

In sub-Saharan Africa, endemic Kaposi's sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi's sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs-naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10-10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with the absence of HIV-1 transcripts in EpKS may suggest an indirect or systemic effect of HIV-1 to promote KS tumorigenesis.

Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. METHODS: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. DISCUSSION: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. TRIAL REGISTRATION: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

Return on Investment of a Breast Cancer Screening Program in Tanzania: Opportunity for Patient and Public Education.

Breast cancer is the second incident and second cause of cancer mortality among women in Tanzania due to late-stage presentation. The screening clinic at the Ocean Road Cancer Institute (ORCI) can help detect cases early and reduce cost of treatment. We calculated the return on investment (ROI) of the ORCI breast screening clinic. Screening and treatment data of all newly diagnosed breast cancer patients seen at ORCI during 2016-2018 were abstracted from the medical records. Also, data on time, resources, and cost of screening and treatment were obtained. The cost of treating screened patients was compared with cost of treating unscreened patients, and differences in cost of treatment were compared with cost of operating the screening program. Of the 730 total patients, 58 were screened prior to treatment, and 672 were not. There was no significant difference between stage at diagnosis and treatments received by screened and unscreened patients (79.3% late- stage vs 72.2% late-stage diagnosis, respectively (p = .531), or cost of treatment between the two groups (cost, in Tanzanian Shillings, for screened (2,167,155.14 or $954.27) vs unscreened (1,918,592.28 or $844.52), (p = .355). There was also no significant difference in cost of treatment between the screened and unscreened groups and a slightly negative ROI (- 0.05%) from implementing the program. The breast screening clinic in Tanzania has not yet proven its cost-effectiveness in reducing stage with screening. The likelihood that patients have utilized the clinic for treatment rather than early detection is a possible reason for the lack of cost-effectiveness. Future studies should focus on educational initiatives to encourage screening at early disease stage. Public education should increase awareness about the clinic for early detection. The experience of this program is ideal for dissemination to other low-income countries that are initiating cancer early detection and cancer education programs.

Views from Multidisciplinary Oncology Clinicians on Strengthening Cancer Care Delivery Systems in Tanzania.

BACKGROUND: In response to the increasing burden of cancer in Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children launched National Cancer Treatment Guidelines (TNCTG) in February 2020. The guidelines aimed to improve and standardize oncology care in the country. At Ocean Road Cancer Institute (ORCI), we developed a theory-informed implementation strategy to promote guideline-concordant care. As part of the situation analysis for implementation strategy development, we conducted focus group discussions to evaluate clinical systems and contextual factors that influence guideline-based practice prior to the launch of the TNCTG. MATERIALS AND METHODS: In June 2019, three focus group discussions were conducted with a total of 21 oncology clinicians at ORCI, stratified by profession. A discussion guide was used to stimulate dialogue about facilitators and barriers to delivery of guideline-concordant care. Discussions were audio recorded, transcribed, translated, and analyzed using thematic framework analysis. RESULTS: Participants identified factors both within the inner context of ORCI clinical systems and outside of ORCI. Themes within the clinical systems included capacity and infrastructure, information technology, communication, efficiency, and quality of services provided. Contextual factors external to ORCI included interinstitutional coordination, oncology capacity in peripheral hospitals, public awareness and beliefs, and financial barriers. Participants provided pragmatic suggestions for strengthening cancer care delivery in Tanzania. CONCLUSION: Our results highlight several barriers and facilitators within and outside of the clinical systems at ORCI that may affect uptake of the TNCTG. Our findings were used to inform a broader guideline implementation strategy, in an effort to improve uptake of the TNCTGs at ORCI. IMPLICATIONS FOR PRACTICE: This study provides an assessment of cancer care delivery systems in a low resource setting from the unique perspectives of local multidisciplinary oncology clinicians. Situational analysis of contextual factors that are likely to influence guideline implementation outcomes is the first step of developing an implementation strategy for cancer treatment guidelines. Many of the barriers identified in this study represent actionable targets that will inform the next phases of our implementation strategy for guideline-concordant cancer care in Tanzania and comparable settings.

Downstaging of cervical cancer in Tanzania over a 16-year period.

Globally, the highest cervical cancer mortality rates are found in East Africa. Visual inspection with acetic acid (VIA)-based screening in resource-poor settings has been shown to decrease the proportion of women presenting with late-stage cervical cancer, a process known as clinical downstaging. The only cancer treatment center in Tanzania, Ocean Road Cancer Institute (ORCI) in Dar es Salaam, opened a VIA-based cervical cancer screening program in 2002. We reviewed 6,676 medical records of cervical cancer patients at the ORCI from 2002-2011 to 2014-2018 for stage at diagnosis and screening status, among other variables. We investigated whether clinical downstaging occurred in this period among women screened at the ORCI, when compared to unscreened women. Our results indicated that the proportion of women presenting with late-stage cervical cancer among women screened at the ORCI decreased by 27.7% over the 16-year period (χ2 = 16.99; p = 0.0002). Among unscreened women, a non-significant 13.2% decrease in late-stage disease was observed (χ2 = 1.74; p = 0.4179). Our results suggest clinical downstaging occurred among women screened at the ORCI over the 16-year period, and this difference may be attributed to the screening program as the same decrease in stage was not observed among unscreened women during the same time period. At present, less than one percent of Tanzanian women receive yearly cervical cancer screenings. Access to screening through expansion of the ORCI screening clinic and the creation of more clinics should be prioritized.

HPV types, cervical high-grade lesions and risk factors for oncogenic human papillomavirus infection among 3416 Tanzanian women.

OBJECTIVE: The objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to describe risk factors for HR HPV among HIV-positive and HIV-negative women in Tanzania. METHODOLOGY: A cross-sectional study was conducted in existing cervical cancer screening clinics in Kilimanjaro and Dar es Salaam. Cervical specimens were obtained from women aged 25-60 years. Samples were shipped to Denmark for cytological examination, and to Germany for HR HPV testing (using Hybrid Capture 2) and genotyping (using LiPaExtra). Risk factors associated with HPV were assessed by multivariable logistic regression analysis. RESULT: Altogether, 4080 women were recruited with 3416 women contributing data for the present paper, including 609 HIV-positive women and 2807 HIV-negative women. The overall HR HPV prevalence was 18.9%, whereas the HR HPV prevalence in women with high-grade squamous intraepithelial lesions (HSILs) was 92.7%. Among HPV-positive women with HSIL, HPV16 (32.5%) and HPV58 (19.3%) were the the most common types followed by HPV18 (16.7%) and HPV52 (16.7%). Factors associated with HR HPV included younger age, increasing number of partners and early age at first intercourse. Similar risk factors were found among HIV-positive and HIV-negative women. In addition, among HIV-positive women, those with CD4 counts <200 cells/mm3 had an increased risk of HR HPV (OR 2.2; 95% CI 1.2 to 4.8) compared with individuals with CD4 count ≥500 cells/mm3. CONCLUSION: Given the HPV distribution among Tanzanian women, the current HPV vaccination in Tanzania using quadrivalent vaccine may be considered replaced by the nonavalent vaccine in the future. In addition, appropriate antiretroviral treatment management including monitoring of viremia may decrease the burden of HR HPV in HIV-positive women.

Agreement between careHPV and hybrid capture 2 in detecting high-risk HPV in women in Tanzania.

INTRODUCTION: Visual inspection of the cervix with acetic acid is used to control the burden of cervical cancer in low- and middle-income countries. This method has some limitations and HPV DNA testing may be an alternative, but it is expensive and requires a laboratory setup. Cheaper and faster HPV tests have been developed. This study describe the agreement between a fast HPV test (careHPV) and hybrid capture 2 (HC2) in detection of high-risk HPV among Tanzanian women. MATERIAL AND METHODS: The study involved women attending routine cervical cancer screening at the Ocean Road Cancer Institute and Kilimanjaro Christian Medical Centre in Tanzania. The women were offered HIV testing. Two cervical samples were subsequently obtained; the first sample was processed at the clinics using careHPV and the second sample was transported to Denmark and Germany for cytology and HC2 analysis. Kappa statistic was calculated to assess the agreement between careHPV and HC2. The sensitivity, specificity and predictive values of careHPV were calculated using HC2 as reference. The analyses were done for the overall study population and stratified by testing site and HIV status. RESULTS: A total of 4080 women were enrolled, with 437 being excluded due to invalid information, lack of careHPV or HC2 results. Overall agreement between the tests was substantial with a kappa value of 0.69 (95% confidence interval [CI] 0.66-0.72). The sensitivity and specificity of careHPV was 90.7% (95% CI 89.6-91.8) and 84.2% (95% CI 81.2-86.8), respectively. The agreement was similar in the stratified analyses where the kappa values were 0.75 (95% CI 0.70-0.79) in women aged 25-34, 0.66 (95% CI 0.62-0.70) in women aged 35-60, 0.73 (95% CI 0.70-0.77) at the Ocean Road Cancer Institute, 0.64 (95% CI 0.60-0.69) at the Kilimanjaro Christian Medical Center, 0.73 (95% CI 0.68-0.79) in HIV-positive and 0.66 (95% CI 0.63-0.70) in HIV-negative women. The kappa value of 0.64 (95% CI 0.39-0.88) for cervical high-grade lesions indicates a substantial agreement between careHPV and HC2 in detecting HPV among women with cervical high-grade lesions. CONCLUSIONS: A substantial agreement was found between careHPV and HC2 in detecting HPV overall as well as detecting HPV among women with cervical high-grade lesions. However, given the limited resources available in low and middle-income countries, the HPV testing assay should be weighed against the cost-effectiveness of the test.

The association between human papillomavirus and cervical high-grade cytology among HIV-positive and HIV-negative Tanzanian women: A cross-sectional study.

INTRODUCTION: Human papillomavirus (HPV) is the causative agent of precancerous lesions and cervical cancer, cervical cancer being the leading cause of deaths in Tanzanian women. Early detection and treatment of precancerous lesions are important in the prevention of cervical cancer cases. MATERIAL AND METHODS: We conducted a cross-sectional study among 3390 Tanzanian women aged 25-60 years. Information on lifestyle habits was collected, and women underwent gynecological examination with collection of cervical cells for conventional cytological and HPV testing. Blood samples were tested for HIV. The association between cervical high-grade cytology (HGC) and potential risk factors was examined using multivariable logistic regression adjusting for age and high-risk HPV (HR-HPV). RESULTS: The prevalence of HGC was 3.6% and of low-grade cytology was 8.3%. In women who were both HR-HPV-positive and HIV-positive, the prevalence of HGC was 28.3%. It increased by age and was 47% among women aged 50-60 years. Women, who had their sexual debut at age 9-15 years and 16-18 years, respectively, had 2.5 and 2.4 times increased odds of HGC compared with women whose sexual debut was at age 21 years and older. HIV-positive women had increased odds of HGC in comparison with HIV-negative women after adjustment for age (odds ratio [OR] 2.95, 95% CI 1.92-4.54). HR-HPV-positive women had nearly 100-fold increased odds of HGC compared with HR-HPV-negative women (OR 96.6, 95% CI 48.0-194), and this estimate was higher among HIV-positive women (OR 152.2, 95% CI 36.1-642.0). CONCLUSIONS: Increasing age, early age at first intercourse, HR-HPV, and HIV infections were associated with a substantially increased risk of HGC.

Developing Research Education Groups in African Cancer Centers: The Experience in Tanzania.

Research productivity and outcomes of junior researchers are usually correlated with the degree and quality of mentorship they receive. A bottom-up approach was followed to develop a research group at the Ocean Road Cancer Institute (ORCI), the major cancer center in Tanzania, to build upon the existing clinical and research resources and institutional global collaborations. The ORCI is a clinical center focused on radio- and chemo-therapy treatment of cancer patients from all over Tanzania. In addition, ORCI has a long-standing early detection program for educating women and screening them for cervical cancer. The ORCI physicians have been exposed to cancer research for the past 20 years through non-degree and degree training in the USA and Europe. In addition, US and European groups have been conducting collaborative research and training of oncologists and graduate students at ORCI. The exposure to research through the above-listed venues motivated the clinicians at ORCI to develop their own Research Club (RC) to learn about research methods, seek independent funding, and outline a research agenda for cancer research in Tanzania. However, it seems that mentorship is needed to help the RC members apply the lessons learned from didactic teaching. Mentorship is also needed to enable the RC members to utilize the enormous clinical and epidemiologic data generated by the institutional programs for prevention, treatment, and follow up of patients. This manuscript describes the inception of the program and its achievements, limitations, and suggested opportunities for improvement as a possible model for other LMICs.

Field Research Experience of Medical Students: Learning and Translation from Global to Underserved US Settings.

While most medical schools in the USA provide opportunities for global health experiences, global health education is not included consistently or emphasized adequately in many medical school curricula. The City University of New York Medical School (CSOM) has a mission to educate and train students who are traditionally underrepresented in medicine to practice primary care in medically underserved communities in New York. This manuscript documents the experience of the CSOM in expanding global health education by introducing a new global health cancer training program, partnering with clinicians at the Ocean Road Cancer Institute (ORCI) in Tanzania. This manuscript illustrates the following points: (1) the CSOM curriculum that focuses on community health and social medicine; (2) the process by which students learn by developing research proposals for global cancer; (3) the field research experience and lessons learned; (4) learning about cancer and medicine in a developing country; and (5) lessons learned for translation from global to domestic underserved populations. We also suggest a checklist for future students interested in pursuing global cancer education and research, and recommendations for maximizing learning and career development of students interested in global cancer research and its application to underserved populations in the USA.

RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment. Our approach is to characterize and compare the gene expression profile in KS lesions versus non-cancer tissues from the same individual. Such comparisons could identify pathways critical for KS formation and maintenance. This is the first study that utilized high throughput RNA-seq to characterize the viral and cellular transcriptome in tumor and non-cancer biopsies of African epidemic KS patients. These patients were treated anti-retroviral therapy with undetectable HIV-1 plasma viral load. We found remarkable variability in the viral transcriptome among these patients, with viral latency and immune modulation genes most abundantly expressed. The presence of KSHV also significantly affected the cellular transcriptome profile. Specifically, genes involved in lipid and glucose metabolism disorder pathways were substantially affected. Moreover, infiltration of immune cells into the tumor did not prevent KS formation, suggesting some functional deficits of these cells. Lastly, we found only minimal overlaps between our in vivo cellular transcriptome dataset with those from in vitro studies, reflecting the limitation of in vitro models in representing tumor lesions. These findings could lead to the identification of diagnostic and therapeutic markers for KS, and will provide bases for further mechanistic studies on the functions of both viral and cellular genes that are involved.

Quantifying the under-estimation of cervical Cancer in remote regions of Tanzania.

BACKGROUND: Cervical cancer is the most common cancer among women in Sub-Saharan countries, including Tanzania. While early detection and diagnosis are available in some parts of this large country, radiotherapy has been only available at the Ocean Road Cancer Institute (ORCI), in the capital city of Dar es Salaam and is just starting in a few regions. METHODS: The objective of this study was to compare the observed incidence of cervical cancer for the two remote regions of Mwanza in western Tanzania and Mbeya in southern Tanzania, based on their patients treated at the ORCI from 2011 to 2014. RESULTS: The number patients referred and treated at ORCI were (120 from Mwanza, and 171 from Mbeya, representing 24.6 and 32.8% of the patients histopathologically confirmed in the two sites, respectively. The results showed significant underestimation of cervical cancer in the two regions. The vast majority of patients who were histopathologically-confirmed in their local regions (73.92% from Mwanza and 65.1% from Mbeya), but did not receive the needed radiotherapy treatment at the ORCI. The estimated incidence for the two regions based on the number of patients treated at the ORCI were underestimated by 53.9% for Mwanza and 68.9% for Mbeya. CONCLUSIONS: Local establishment of radiotherapy treatment facilities in remote regions in Tanzania and similar other low-income countries is essential for providing effective treatment and improving survival of diagnosed cervical cancer patients. Linkage between the records of local remote hospitals and the main cancer treatment center in the capital city can also help support the emerging the population-based cancer registry at ORCI.

"The best thing is that you are doing it for yourself" - perspectives on acceptability and feasibility of HPV self-sampling among cervical cancer screening clients in Tanzania: a qualitative pilot study.

BACKGROUND: Cervical cancer is the most common type of cancer in sub-Saharan Africa, and it is also the cancer disease that most women die from. The high mortality rate is partly due to low attendance rates to screening services and low sensitivity of visual inspection with acetic acid, which is the standard screening method used in screening programs in sub-Saharan Africa. In order to overcome of the burden of disease new screening strategies and methods are warranted. This study aims to explore the acceptability and feasibility of HPV self-sampling compared to provider-based sampling among cervical cancer screening clients living in Dar es Salaam. METHODS: Women attending cervical cancer screening at Ocean Road Cancer Institute in Dar es Salaam, Tanzania between February - April 2017 were invited into the study. The participants had (1) a provider-collected sample, and (2) a self-sample for HPV on top of the regular cervical cancer screening. 50% of the participants conducted the self-sample after receiving a written instruction guide of how to collect the sample (written). The other 50% received both the written and an oral introduction to self-sampling (written+). All participants could ask for nurse assistance during self-sample collection if needed. Individual semi-structured interviews were conducted with the participants post sample collection. Data collection stopped when saturation was reached. Data were analysed using a thematic content analysis. RESULTS: Twenty-one women participated in the study. Regardless of how women were introduced to the self-sample (written or written+), there was a high demand for nurse presence as they felt uncertain of their personal capabilities to collect the self-sample correctly. However, as long as nurse assistance was an option most women perceived self-sampling as easy and comfortable though few experienced bleeding and pain. The majority of women preferred self-sampling over provider-sampling primarily due to the method being more private than the provider-sampling. CONCLUSIONS: HPV self-sampling was well-perceived and accepted, however, for the method to be feasible a nurse needed to be present. HPV Self-sampling may be an alternative method to increase uptake of cervical cancer screening. Larger quantitative studies are recommended to support the study findings.

Effectiveness of One-Way Text Messaging on Attendance to Follow-Up Cervical Cancer Screening Among Human Papillomavirus-Positive Tanzanian Women (Connected2Care): Parallel-Group Randomized Controlled Trial.

BACKGROUND: Rapid human papillomavirus (HPV) DNA testing is an emerging cervical cancer screening strategy in resource-limited countries, yet it requires follow-up of women who test HPV positive. OBJECTIVE: This study aimed to determine if one-way text messages improved attendance to a 14-month follow-up cervical cancer screening among HPV-positive women. METHODS: This multicenter, parallel-group randomized controlled trial was conducted at 3 hospitals in Tanzania. Eligible participants were aged between 25 and 60 years, had tested positive to a rapid HPV test during a patient-initiated screening, had been informed of their HPV result, and had a private mobile phone with a valid number. Participants were randomly assigned in a 1:1 ratio to the intervention or control group through an incorporated algorithm in the text message system. The intervention group received one-way text messages, and the control group received no text messages. The primary outcome was attendance at a 14-month health provider-initiated follow-up screening. Participants were not blinded, but outcome assessors were. The analysis was based on intention to treat. RESULTS: Between August 2015 and July 2017, 4080 women were screened for cervical cancer, of which 705 were included in this trial-358 women were allocated to the intervention group, and 347 women were allocated to the control group. Moreover, 16 women were excluded before the analysis because they developed cervical cancer or died (8 from each group). In the intervention group, 24.0% (84/350) women attended their follow-up screening, and in the control group, 23.8% (80/335) women attended their follow-up screening (risk ratio 1.02, 95% CI 0.79-1.33). CONCLUSIONS: Attendance to a health provider-initiated follow-up cervical cancer screening among HPV-positive women was strikingly low, and one-way text messages did not improve the attendance rate. Implementation of rapid HPV testing as a primary screening method at the clinic level entails the challenge of ensuring a proper follow-up of women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02509702; https://clinicaltrials.gov/ct2/show/NCT02509702. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10.2196/15863.

Similar Immunological Profiles Between African Endemic and Human Immunodeficiency Virus Type 1-Associated Epidemic Kaposi Sarcoma (KS) Patients Reveal the Primary Role of KS-Associated Herpesvirus in KS Pathogenesis.

BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) is etiologically linked to all KS forms, but mechanisms underlying KS development are unclear. The incidence of KS in human immunodeficiency virus type 1-infected (HIV-1+) individuals implicates immune dysregulation; however, the lack of characterization of KSHV immune responses in endemic KS makes the role of HIV-1 unclear. The study objective was to investigate the HIV-1 and KSHV roles in viral nucleic acid detection, antibody responses, and cytokine responses in polymerase chain reaction-confirmed epidemic KS and endemic KS patients and non-cancer controls from sub-Saharan Africa. METHODS: KSHV viral DNA (vDNA), total anti-KSHV antibody, KSHV neutralizing antibody (nAb), and cytokines were quantified. RESULTS: KSHV vDNA was detectable in tumors but variably in plasma and peripheral blood mononuclear cells. Consistent with elevated antibody-associated cytokines (interleukin [IL] 6, IL-5, and IL-10), nAb titers were higher in epidemic KS and endemic KS patients than in controls (P < .05). Despite HIV-1 coinfection in epidemic KS, nAb titers were similar between epidemic KS and endemic KS patients (P = 0.3). CONCLUSIONS: Similarities in antibody and cytokine responses between epidemic and endemic KS patients suggest that KSHV drives KS pathogenesis, whereas HIV-1 exacerbates it.

Barriers and Facilitators to Cervical Cancer Screening, Diagnosis, Follow-Up Care and Treatment: Perspectives of Human Immunodeficiency Virus-Positive Women and Health Care Practitioners in Tanzania.

BACKGROUND: This study was conducted to identify barriers and facilitators to cervical cancer screening, diagnosis, follow-up care, and treatment among human immunodeficiency virus (HIV)-infected women and clinicians and to explore the acceptability of patient navigators in Tanzania. MATERIALS AND METHODS: In 2012, we conducted four focus groups, two with HIV-positive women and two with clinicians who perform cervical cancer screening, diagnosis, follow-up care, and treatment. Transcriptions were analyzed using thematic analysis. RESULTS: Findings from the patient focus groups indicate the prevalence of fear and stigma surrounding cervical cancer as well as a lack of information and access to screening and treatment. The clinician focus groups identified numerous barriers to screening, diagnosis, follow-up care, and treatment. Participants in both types of groups agreed that a patient navigation program would be an effective way to help women navigate across the cancer continuum of care including screening, diagnosis, follow-up care, and treatment. CONCLUSION: Given the fear, stigma, misinformation, and lack of resources surrounding cervical cancer, it is not surprising that patient navigation would be welcomed by patients and providers. IMPLICATIONS FOR PRACTICE: This article identifies specific barriers to cervical cancer screening and treatment from the perspectives of both clinicians and patients in Tanzania and describes the acceptability of the concept of patient navigation.