Molecular characterization of hepatitis B virus in blood donors in Botswana.

Hepatitis B virus (HBV) poses a significant threat to blood transfusion safety in sub-Saharan Africa (SSA) where allogeneic blood donations are screened serologically, and more sensitive nucleic acid tests (NATs) are utilized infrequently. HBV strains circulating among blood donors in Botswana are not yet characterized. We designed a cross-sectional study to determine the HBV sub-genotypes and prevalence of hepatitis B surface antigen (HBsAg) among blood donors between November 2014 and October 2015. A total of 12,575 blood donations were screened for HBsAg and 50 consecutive plasma samples were selected for genotyping from confirmed HBsAg+ donations. Overlapping Pol and complete S (Pol/S) open reading frames (ORFs) were sequenced from extracted HBV DNA. To identify any signature amino acids, mutations were compared to sequences from a cohort of chronic HBV patients co-infected with HIV and were treatment naïve. The prevalence of HBsAg+ blood donors was 1.02% (95% CI 0.9-1.2%), and the circulating sub-genotypes were A1 serotype adw2 (36.1%), D2 serotype ayw2 (2.9%), and D3 serotypes ayw 1/2 (58.3%). Prevalence of escape mutations was 14% from HBV isolates of blood donors and 15% from isolates of HBV/HIV co-infected patients (p = 0.6926). The escape mutations sP120L, sG130R, sY134H, and sD144A were identified predominantly among HBV isolates from blood donors. These escape mutations have been associated with accelerated HBV sequelae [e.g., liver cirrhosis (LC) and hepatocellular carcinoma (HCC)], failure to detect HBsAg, inability to respond to immunoglobulin (Ig) therapy, and HBV vaccine escape. Characterizing the HBV burden, circulating sub-genotypes, and clinically relevant mutations among blood donors in Botswana is important to elucidate the efficacy of currently available vaccines, predicting HBV-transmission patterns, understanding the cohort's risk to HBV-related complications, and to developing prevention strategies and effective genotype-based antiretroviral therapies.

Teledermatology as a Means to Provide Multispecialty Care: A Case of Global Specialty Collaboration.

Telemedicine can serve as a platform for specialty collaboration and potentially address the lack of specialized and subspecialized care globally. In this article we present a case in which the use of teledermatology facilitated global collaboration between multiple specialists and subspecialists, resulting in high-quality care of a child from a remote area of Botswana. We present the lessons learned and factors that should be considered when engaging in global specialty collaboration, especially between developed and developing countries. We also discuss the potential limitations of telemedicine when used within a global context. With these considerations in mind, global specialty collaboration facilitated by telemedicine can provide a potential solution to the lack of access to specialized and subspecialized care.

Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

BACKGROUND: Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. METHODS: Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). RESULTS: Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). CONCLUSION: Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. IMPLICATIONS FOR PRACTICE: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total), regular longitudinal contact with the health system, through quarterly doctor visits for HIV management, was not successful in providing faster linkages into oncology care. However, patients who used traditional medicine/healers engaged in cancer care faster, indicating potential for leveraging traditional healers as partners in early cancer detection. New strategies are urgently needed to facilitate diagnosis and timely treatment of cancer in low- and middle-income countries.

Oncogenic viral prevalence in invasive vulvar cancer specimens from human immunodeficiency virus-positive and -negative women in Botswana.

OBJECTIVE: The primary aim of this study was to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with human immunodeficiency virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world. METHODS: A cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) viral testing were done for Epstein-Barr virus, human papillomavirus (HPV) strains, and Kaposi sarcoma herpesvirus, and PCR viral testing alone was done for John Cunningham virus. RESULTS: Human papillomavirus prevalence by PCR was 100% (35/35) among tested samples. Human papillomavirus type 16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). Kaposi sarcoma herpesvirus prevalence by PCR had a significant association with HIV status (P = 0.013), but not by IHC (P = 0.650). CONCLUSIONS: The high burden of HPV, specifically HPV16, in vulvar squamous cell cancer in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses Kaposi sarcoma herpesvirus and Epstein-Barr virus were also more prevalent in our study population, although their potential role in vulvar squamous cell cancer pathology is unclear.

Prevalence of human papillomavirus genotypes and associated cervical squamous intraepithelial lesions in HIV-infected women in Botswana.

Human papillomaviruses (HPV) constitute one of the most prevalent sexually transmitted infections and are the etiological agents for invasive cervical cancer, the predominant cancer among women in Botswana. However, the prevalence of HPV genotypes in Botswana has yet to be reported. One hundred thirty-nine endocervical swabs were taken at baseline from HIV-1 infected, HSV-2 seropositive women enrolled in a longitudinal cohort study designed to assess the influence of herpes simplex virus-2 (HSV-2) infection on genital tract shedding of HIV-1. Extracted DNA was evaluated for the presence of low-risk and high-risk HPV using the Roche Linear Array. Genotyping identified HPV in 95 of 139 women of which 61/95 were infected with high-risk HPV and 56/95 with low-risk HPV. The median number of genotypes was 2 (IQR: 1-4). The most prevalent HPV genotype in HIV-infected women was HPV 58. Abnormal cervical cytology was detected in 87/127 women and was associated with contemporaneous HPV infection (RR = 1.43, 95% CI: 1.05-1.93; P = 0.02). HPV prevalence was high among HIV-infected women with infection by multiple genotypes being widespread. The associations attributed to specific oncogenic HPV subtypes and cervical squamous intraepithelial lesions presented here provide critical information to inform future vaccine policy within Botswana.

Accuracy of Pathologic Diagnosis in Patients With Lymphoma and Survival: A Prospective Analysis From Botswana.

PURPOSE: With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival. METHODS: Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard. RESULTS: The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL. CONCLUSION: In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries.

Clinicopathologic Features of Peripheral T-Cell Lymphoma in Sub-Saharan Africa.

OBJECTIVES: Peripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare. Subtype distribution varies by geographic location; however, data from sub-Saharan Africa (SSA) are lacking. We sought to elucidate clinicopathologic features of PTCL in SSA. METHODS: We reviewed PTCL consultation cases from three SSA countries. PTCL subtype was determined per 2017 World Health Organization classification. Cases with sufficient material were evaluated by polymerase chain reaction for human T-cell leukemia virus type 1 (HTLV-1) and T-cell receptor γ (TCRG) rearrangement. RESULTS: Among 32 cases, median age was 45 years and male-to-female ratio was 1.7. Thirty (94%) of 32 cases required additional workup for subclassification. PTCL, not otherwise specified (PTCL-NOS) was the most common subtype (13/32, 41%), followed by PTCL with T-follicular helper phenotype (6/32, 19%) and systemic anaplastic large cell lymphoma (6/32, 19%). Four (16%) of 25 cases were Epstein-Barr virus positive (EBV+) (2/2 extranodal natural killer/T-cell lymphoma, 1/13 PTCL-NOS, and 1/4 angioimmunoblastic T-cell lymphoma with EBV+ immunoblasts). Two (15%) of 13 patients with PTCL-NOS were human immunodeficiency virus positive. No cases with evaluable DNA (0/15) were HTLV-1 positive, and 9 of 10 showed clonal TCRG rearrangements. CONCLUSIONS: In comparison to Western studies, PTCLs from SSA show similar subtype distribution and male predominance but a younger age at diagnosis. Appropriate diagnosis of PTCL requires extensive ancillary testing not readily available in low-income countries, including much of SSA.

Dermatology-Driven Quality Improvement Interventions to Decrease Diagnostic Delays for Kaposi Sarcoma in Botswana.

PURPOSE: Kaposi sarcoma (KS) is an HIV-associated skin cancer that is highly prevalent in Botswana and associated with significant morbidity and mortality. Histopathology-confirmed diagnosis is required for chemotherapeutic interventions in Botswana, which creates barriers to care because of limited biopsy and pathology services. We sought to understand the role a dermatology specialist can play in improving KS care through quality improvement (QI) initiatives to reduce histologic turnaround times (TATs) for KS. METHODS: Employment of a dermatology specialist within a public health care system that previously lacked a local dermatologist generated quality improvements in KS care. Retrospective review identified patients diagnosed with KS by skin biopsy in the predermatology QI interval (January 1, 2015, to December 31, 2015) versus the postdermatology QI interval (January 1, 2016, to November 31, 2017). Histology TATs and clinical characteristics were recorded. A t test compared the median histology TATs in the pre- and post-QI intervals. RESULTS: A total of 192 cases of KS were diagnosed by skin biopsy. Nearly all (98.4%) were HIV-positive; and 52.8% of patients were male with a median age of 39 years. Median TAT in the postdermatology QI interval was 11 days (interquartile range, 12-23 days) compared with 32 days in the predermatology QI interval (interquartile range, 24-56 days; P < .00). CONCLUSION: Dermatology-led QI initiatives to improve multispecialty care coordination can significantly decrease histology TATs for KS. The reduction of diagnostic delays is a key first step to decreasing the morbidity and mortality associated with this cancer in resource-limited settings.

Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana.

BACKGROUND: To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status. METHODS: This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records. RESULTS: A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44-66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER-/PR-/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER-/PR-/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals. CONCLUSIONS: Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.

A retrospective review of patients with Kaposi's sarcoma in Botswana.

BACKGROUND: Despite widespread antiretroviral coverage in Botswana, Kaposi's sarcoma (KS) remains among the most common malignancies. To date, adult KS in Botswana is not well characterized. The diagnosis relies on clinical suspicion that is often confirmed by histopathology given the implications of treatment; however, this poses a significant resource burden. METHODS: We conducted a retrospective review of the cohort of patients biopsied for possible KS at Princess Marina Hospital, the main dermatology referral site in Botswana, from September 2008 through June 2015 to describe the demographics, human immunodeficiency virus (HIV) characteristics, and clinical presentations of these patients. Histopathologic diagnoses were reviewed, and positive predictive value (PPV) was used to characterize the accuracy of clinical suspicion of KS. RESULTS: A total of 441 patients received 450 biopsies where KS was on the differential diagnosis, and 239 patients (54%) were ultimately diagnosed with KS. The KS cohort was more likely to be male (58% vs. 37%, P < 0.001), HIV positive (94% vs. 85%, P < 0.05), and have lower CD4 counts at the time of biopsy (274 cells/µl vs. 362 cells/µl, P < 0.05). The PPV of clinical suspicion of KS was 58%. When KS was not histopathologically diagnosed, clinically benign diseases were found in 17%, medically significant conditions requiring alternative therapies in 78%, and life-threatening diseases in 5%. DISCUSSION: Our study reinforces the risk factors in development of KS. The poor PPV supports the important role of histology in KS diagnosis to both ensure appropriate treatment and prevent overtreatment. Improved accessibility to biopsy and augmentation of local dermatopathologic services would likely improve diagnostic accuracy and treatment.

Breast Cancer Pathology Turnaround Time in Botswana.

PURPOSE: Quality pathology is critical for timely diagnosis and management of breast cancer. Few studies have analyzed pathology turnaround time (TAT) in sub-Saharan Africa. The purpose of this study was to quantify TAT for breast cancer specimens processed by the National Health Laboratory and Diagnofirm Laboratory in Gaborone, Botswana, and additionally compare TAT before and after 2012 to evaluate the effect of pathology scale-up interventions by the Ministry of Health and Wellness. METHODS: Retrospective analyses of TAT were performed for breast specimens submitted to the two laboratories from 2011 to 2015. TAT was calculated as the time from specimen collection and receipt in the laboratory to the date of final report sign-out. Descriptive statistics and rank sum test were used to compare temporal trends in TAT before and after 2012. RESULTS: A total of 158 breast biopsy, 219 surgical, and 218 immunohistochemistry (IHC) specimens were analyzed. The median TAT in 2015 was 6 and 7 days for biopsy and IHC specimens, respectively, and 57.5 days for surgical specimens. There was a significant decrease in median TAT for biopsy specimens from 21.5 days in 2011 to 2012 compared with 8 days in 2013 to 2015 ( P < .001). There was also a significant decrease in median TAT for IHC specimens during the same period ( P < .001). However, there was no significant decline in median TAT for surgical specimens. CONCLUSION: The scale-up of pathology personnel and infrastructure by the Ministry of Health and Wellness significantly reduced median TAT for biopsy and IHC specimens. TAT for surgical specimens remains suboptimal. Efforts are currently under way to decrease TAT for surgical specimens to 7 days.

Impact of HIV Infection on the Clinical Presentation and Survival of Non-Hodgkin Lymphoma: A Prospective Observational Study From Botswana.

PURPOSE: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)-an AIDS-defining cancer-in the country. PATIENTS AND METHODS: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. RESULTS: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001). CONCLUSION: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival.

Impact of Human Immunodeficiency Virus Infection on Survival and Acute Toxicities From Chemoradiation Therapy for Cervical Cancer Patients in a Limited-Resource Setting.

PURPOSE: To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. METHODS AND MATERIALS: Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. RESULTS: Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03). CONCLUSIONS: Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status.

Multidisciplinary Gynecologic Oncology Clinic in Botswana: A Model for Multidisciplinary Oncology Care in Low- and Middle-Income Settings.

PURPOSE: Cervical cancer is a major cause of mortality in low- and middle-income countries (LMICs) and the most common cancer diagnosed in women in Botswana. Most women present with locally advanced disease, requiring chemotherapy and radiation. Care co-ordination requires input from a multidisciplinary team (MDT) to deliver appropriate, timely treatment. However, there are limited published examples of MDT implementation in LMICs. METHODS: In May 2015, a weekly MDT clinic for gynecologic cancer care was initiated at Botswana's national referral facility. The MDT clinic served as a forum for discussion and coordination of patients with gynecologic cancer and consisted of a gynecologist, pathologist, medical oncologist, radiation oncologist, palliative care specialist, and nurse coordinator. RESULTS: Between May 2015 and December 2015, 135 patients were seen in the MDT clinic. The mean age of the patients was 49 years. Most (60%) of the patients were HIV positive. The most common diagnosis was cervical cancer (60%), followed by high-grade cervical intraepithelial neoplastic lesions (12%) and vulvar cancer (11%). Only data up to September 2015 were assessed for treatment delays. It was found that only 38% of patients needed more than one visit for care coordination before treatment initiation. Among patients with cervical cancer, the median delay from date of biopsy to start of radiation treatment was 39 days (interquartile range, 34 to 57 days) for patients treated after MDT initiation, compared with 108 days (interquartile range, 71 to 147 days) for patients treated before MDT initiation (P < .001). CONCLUSION: Implementation of MDT clinics in LMICs is feasible and can help reduce delays in treatment initiation, as demonstrated by a gynecologic MDT clinic in Botswana. Streamlining care through MDT clinics can enhance care coordination and improve clinical outcomes. This model can apply to cancer care in other LMICs.

HIV Infection and Survival Among Women With Cervical Cancer.

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.

Cancer Incidence following Expansion of HIV Treatment in Botswana.

BACKGROUND: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa. METHODS: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003-2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage. FINDINGS: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi's sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%). INTERPRETATION: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa.