CANCER BURDEN AMONG HIV-INFECTED PERSONS ON ANTIRETROVIRAL THERAPY IN MALAWI: A RECORD LINKAGE STUDY

Sub-Saharan Africa represents 70% of the global number of people living with HIV. The regional HIV epidemic is reflected in the cancer burden, where AIDS-defining cancers are among the most common malignancies in the region. Early access and continued adherence to antiretroviral therapy (ART) may reduce the risk of certain cancers among the HIV population. Local epidemiological data are needed to characterize the cancer burden among African HIV populations during the ART era. In the Malawi HIV-Cancer Match Study, we used algorithms to link cancer cases from the population-based cancer registry of Malawi with electronic medical records from two high volume HIV clinics. We constructed a clinical cohort of 29,000 people who initiated ART from 2000 to 2010 at Lighthouse Trust and Queen Elizabeth Central Hospital. We described implementation of a healthcare data linkage in a resource-constrained setting, common analytical barriers, and solutions. We used Poisson regression to estimate cancer incidence rates and describe the timing of new cancer diagnoses after starting ART. Missing data and misreporting of patient identifiers resulted in a substantial proportion of potential cancer cases being discarded from analysis. Consequently, missing data on potential cancer cases may have diminished sensitivity of the linkage algorithms. Sensitivity analysis of incidence rates was used to address scenarios of uncertainty in the linkage process. Two AIDS-defining malignancies, Kaposi sarcoma (KS) and cervical cancer, were the most common cancers in this young population of ART users who tend to present to care with severe immunosuppression. Most incident KS occurred within the first two years of starting ART, and elevated incidence rates persisted over the course of follow-up in spite of therapy. AIDS-associated non-Hodgkin lymphomas and a heterogeneous spectrum of NADC were also observed, but at low incidence rates. Our study is a baseline against which to monitor the contemporary burden of cancer among people who are now starting ART at earlier stages of HIV, when therapy likely to have a substantial impact on cancer incidence. Descriptive epidemiological data on people living with HIV is important for public health decision makers in Malawi to develop evidence-based cancer control plans targeting high-risk HIV populations.Doctor of Philosoph

Early Experience after Developing a Pathology Laboratory in Malawi, with Emphasis on Cancer Diagnoses

BackgroundDespite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses.Methods and FindingsWe performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99%) with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%). Among cancers, cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91, 11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75, 9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19–1.29) among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14–1.56) among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not.ConclusionsDespite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical information for pathologically confirmed cancers can allow these data to complement population-based registration

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional, and global level in 2020. Proportions of cervical cancer a) diagnosed in women living with HIV (WLHIV), and b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted towards younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Breast cancer disparities in South Carolina: early detection, special programs, and descriptive epidemiology.

A discrepancy exists between mortality and incidence rates between African-American and European-American women in South Carolina. The relationship between tumor grade and the estrogen/ progesterone receptor status is different in African-American and European-American women. African-American women with breast cancer should be encouraged to participate in clinical trials, with the goal of identifying biological factors that might facilitate the detection of tumors at an earlier stage and the development of more effective therapies. The most important of our goals is to design studies to reduce the incidence of the disease and interventions to improve survival and quality of life. The importance of participation in research cannot be overstated. Reproductive factors such as early pregnancy and multiple pregnancies are strongly related to breast cancer risk, however, promotion of these factors as a "prevention strategy," clearly does not lead to cogent, comprehensive public health messages. Data from ecological and migrant studies point clearly to other factors that may be important such as diet. Additional research around primary prevention strategies is needed. In addition, yearly mammograms (secondary prevention) are recommended for women over 50 years old or those with relatives who have developed breast cancer. The Best Chance Network, as a provider of screenings to low-income, uninsured women, has helped to narrow the racial gap in screening that otherwise might exist (see Figures 3 and 4) to a large extent. The determination for timing of surgery after diagnosis needs additional consideration. For example, factors such as effective screening in younger women, timing of screening and surgery in relationship to the ovulatory cycle, and season of screening and surgery may have a great impact on outcomes and may offer some insight into the process of carcinogenesis and therapeutic efficacy. Research into this area is so novel that the impact on possible ethnic disparities is completely unknown. The South Carolina Cancer Disparities Community Network (SCCDCN) has identified the following areas as potential research foci: Identification of small media interventions as an effective strategy to motivate targeted populations, especially those least likely to seek screening for breast cancer and those least likely to participate in research programs (African-Americans). Utilization of breast cancer survivors, self-identified as community natural helpers, can share their experiences with their church congregation. A replication of such a program in South Carolina has great potential because of the strong presence of the church, especially in rural parts of the state. Programs that closely integrate religion with screening women for breast cancer are promising in this state. Development of a mammography registry whereby information on all mammography procedures would be collected within a single database system (much like a central cancer registry). This would aid in identifying population groups that could be targeted for special programs and in the examination and exploration of the most appropriate modalities of detection. Such a resource could also be a useful tool to encourage screening. Thus, this focus area has the potential to benefit epidemiologic and health promotion research on many different levels. Additional breast cancer screening methods should not be overlooked as a potential research focus. Mammography is not the only valid screening method for breast cancer. Magnetic resonance imaging has shown some promise for screening among women with a genetic predisposition for cancer. Another promising avenue is thermography. Because detection rates may depend on age, ethnicity, and breast mammographic characteristics, women for whom regular screening methods do not detect their cancers (e.g. older age, African-American ethnicity, dense breasts) must be identified and other screening methods promoted within these populations. The above-mentioned mammography registry would support this type of research

Associations of patient characteristics with premalignant/malignant and malignant diagnosis in the Kamuzu Central Hospital pathology database between July 1, 2011 and February 28, 2013.

<p>OR = odds ratio. CI = confidence interval. *Bivariable analyses include only specimens with known patient age (n = 2685), gender (n = 2748), or HIV status (n = 328). **Multivariable analyses include only 317 specimens with known patient age, gender, and HIV status.</p

Specimens received in the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013.

<p>Specimens received in the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013.</p

Immunohistochemistry stains being implemented in the Kamuzu Central Hospital pathology laboratory.

<p>HPV = human papillomavirus. LANA = latency-associated nuclear antigen. ER = estrogen receptor. PR = progesterone receptor.</p

Patient, specimen, and diagnosis characteristics in the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013.

<p>SD = standard deviation. *HIV status routinely collected beginning November 2012.</p