Mathewos Assefa

Background: Cervical cancer is the second commonly diagnosed cancer and the second leading cause of cancer death in women in Ethiopia, with rates among the highest worldwide. However, there are limited data on cervical cancer treatment patterns and survival in the country. Herein, we examine treatment patterns and survival of cervical cancer patients treated in Tikur Anbessa Hospital Radiotherapy Center (TAHRC), the only hospital with radiotherapy facility in the country. Methods: Women with histologically verified cervical cancer who were seen in 2014 (January 1, 2014 to December 31, 2014) at TAHRC were included. Information about clinical characteristics and treatments were extracted from the patients’ medical record files. The information on vital status was obtained from medical chart and through telephone calls. Result: Among 242 patients included in the study, the median age at diagnosis was 48 years. The median waiting time for radiotherapy was 5.6 months (range 2 to 9 months). Stage migration occurred in 13% of patients while waiting for radiotherapy. Consequently, the proportion of patients with stage III or IV disease increased from 66% at first consultation to 74% at the initiation of radiotherapy. Among 151 patients treated with curative intent, only 34 (22.5%) of the patients received concurrent chemotherapy while the reaming patients received radiotherapy alone. The 5-year overall survival rate was 28.4% (20.5% in the worst-case scenario). As expected, survival was lower in patients with advanced stage at initiation of radiotherapy and in those treated as palliative care. Conclusion: The survival of cervical cancer patients remains low in Ethiopia because of late presentation and delay in receipt of radiotherapy, leading to stage migration in substantial proportion of the cases. Concerted and coordinated multisectoral efforts are needed to promote early presentation of cervical cancer and to shorten the unacceptable, long waiting time for radiotherapy.

Assefa: There are several reasons and challenges in breast cancer care in low-resource countries. The main reason is late presentation of patients. This is due to a lack of awareness about breast cancer signs and symptoms, particularly in the rural setting. Most people associate cancer with pain and visit a health facility when they feel breast pain. On the other hand, they don’t seek medical advice despite noting breast lumps for months.Also, there is a lack of infrastructure/resources for screening and early detection, limited awareness by health professionals resulting in diagnostic delay and a lack of treatment facilities to give treatment on time for patients coming early – this includes access to surgery, chemotherapy and radiotherapy. Also there are no patient support groups (cancer survivors) to teach general public and patients about chances to survive. In our setting I see patients using traditional medicine and seeking religious solutions like using holy water which may delay diagnosis and treatment.McCormack: Breast cancer is the first or second cause of cancer death in women in almost all countries worldwide. In lower-resource settings, breast cancer needs particular attention because its incidence rates are rising largely due to fertility transitions, whilst the absolute number of women newly diagnosed with this cancer is increasing at an even greater rate amidst the ageing of populations. Thus, for the increasing number of women diagnosed with breast cancer each year, i.e., beyond the 2.1 million women diagnosed globally in 2018, health systems need to ensure early diagnosis and treatment for women with breast cancer in order to avert what will otherwise be a high mortality toll from this treatable cancer (627,000 deaths in 2018).Cubasch: The first part of the problem concerns the changing demographics of these countries. We are dealing with generally growing and aging populations. Historically low breast cancer incidence rates in sub-Saharan Africa are increasing due to a westernized lifestyle. In addition, life expectancy is steadily increasing due to HIV being turned into a controllable, chronic disease due to a successful ART roll out. We now need to brace for a secondary epidemic of cancer and other common NCD.On the other hand, cancer outcomes are much worse than in well-resourced countries; existing health care structures are dysfunctional and there is a lack the resources to deal with the necessary complex multimodality treatment for cancer. The gap between the needs and reality is widening. Our patients will have better access to global media channels and be better informed, while health systems will struggle to deliver appropriate care.Jemal: Breast cancer is increasingly becoming a major public health challenge in low-resource countries for two reasons. First, the burden of the disease is increasing because of increases in the prevalence of known risk factors such as a late child-bearing age, having fewer children per woman, overweight and obesity, and physical inactivity, as well as aging and growth of the population (women) and a shorter duration of breast feeding. Second, the healthcare system is less developed and the healthcare workforce is lacing for timely diagnosis and treatment of breast cancer patients. In most sub-Saharan countries, for example, breast cancer patients are treated without assessing their estrogen-receptor status because of a lack of immunohistochemistry and most surgeries are performed by general surgeons instead of breast surgeons.Pace: As populations age, and with declining burdens of infectious diseases, we are seeing more and more diseases of aging such as breast cancer. The age-specific breast cancer incidence is also rising, likely because of shifts in reproductive risk factors. We know that, in low-income countries, women are typically diagnosed late and with stage III or IV disease, which is a major challenge.Assefa: In low-income countries the double burden of disease, communicable and non-communicable, stretches health system resources. As a result, governments and policy makers are forced to allocate most of the resources for preventive and primary care. Cancer screening and treatment are relatively complex, requiring a tertiary facility with expert trained health professional (radiologist, pathologist, surgeon, oncologist, radiotherapist, and medical physicist, etc., to mention some) and expensive equipment.McCormack: Low breast cancer survival in lower-resource settings, in comparison to high-resource settings, arises from the accumulation of disparities occurring along the entire journey of women with breast cancer. This journey commences during the many months, sometimes over 1 year, prior to the definitive histological diagnosis and continues during the treatment period.Cubasch: First of all, in the South African setting we found that it is not due to a more aggressive cancer biology.However, disparities affect the entire journey of a patient. In the absence of any population screening, the patient usually detects a lump, too often at late stage of disease. Then there is a first contact with the health system, multiple visits and referrals often leading to a delayed diagnosis, further delays with the initiation of chemotherapy, surgery and radiotherapy, non-availability of drugs, and long queues at every step. Many of our patients struggle anyway with hardships of life, money for transport, and concomitant family responsibilities. In other parts of sub-Saharan Africa, patients have to pay for their own diagnostic tests and treatments, which are unaffordable, leading to a nihilistic attitude to cancer.We found that stage on presentation is not only an important predictor of outcome but it is also a useful process marker that offers itself as a target for possible, affordable interventions.Jemal: I think major factors that contribute to the breast cancer disparity in low-resource countries compared to...

Ethiopia lies in the high-risk corridor of esophageal squamous cell carcinoma in East Africa, where individuals with this malignancy often do not report established risk factors, suggesting unidentified etiologies. Here, we report the prevalence of mucosal human papillomavirus (HPV) and of Helicobacter pylori (H. pylori) detection in endoscopy-obtained esophageal and gastroesophageal junction biopsies and in oral cell specimens taken at the time of esophageal cancer diagnosis in a case–control study in Addis Ababa, Ethiopia. DNA extraction was performed from fresh frozen tissue and oral cell pellets obtained with saline solution gargling subsequently fixed with ethanol. Mucosal HPV and H. pylori DNA was detected using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. The proportions of specimens testing positive were expressed as percentages, with binomial 95% confidence intervals. Agreement of results between tissue biopsy and oral cell specimens was estimated using the kappa statistic. Comparison of study participants’ characteristics by test results was done using the Pearson chi-square test. HPV DNA was detected in 1 of 62 tumor specimens (2, 95% confidence interval (CI): 0–9%), corresponding to HPV16 type. HPV DNA was detected in the oral cavity of 7 cases (11, 95% CI: 5–22%) and 4 of 56 matched healthy controls (7, 95% CI: 2–17%), with multiple HPV types detected. Detection of H. pylori DNA was 55% (95% CI: 42–68%), and 20 of 34 H. pylori-positive specimens (59, 95% CI: 41–75%) were positive for the cagA gene. Agreement of detection rates between tissue and oral cells in cases was poor for HPV and for H. pylori. The prevalence of mucosal-type HPV was very low, whereas H. pylori was more commonly detected, with a high proportion testing positive for the pro-inflammatory gene cagA. These novel findings remain to be replicated in larger studies and with the addition of serological determinations to better understand their biological significance in the context of esophageal and gastroesophageal junction cancers.

Emerging evidence associates vitamin D deficiency and vitamin D receptor (VDR) genetic variations with risk for breast cancer. This study investigated the prevalence of vitamin D deficiency and its association with tumor characteristics and the implications of VDR genetic variations for risk of breast cancer in Ethiopia. This unmatched case–control study involved 392 female breast cancer patients and 193 controls. The plasma 25-hydroxyvitamin D (25(OH)D₃) level was quantified in chemotherapy-naïve (N = 112) and tamoxifen-treated patients (N = 89). Genotyping for the VDR common variant alleles rs7975232 (ApaI), rs2228570 (FokI), and rs731236 (TaqI) was done. Eighty-six percent of the patients were vitamin D deficient (p < 0.001). The prevalence of severe vitamin D deficiency (VDR genotype. The rs2228570 GG genotype was associated with increased risk of breast cancer (OR = 1.44, 95% confidence interval = 1.01−2.06). Our result indicates that rs2228570 might be a moderate risk factor for breast cancer development in the Ethiopian population. The high prevalence of severe vitamin D deficiency in treatment-naïve breast cancer patients indicates the need for nutritional supplementation of vitamin D at the time of chemotherapy initiation.

Rapid Ethical Assessment (REA) is an approach used to design context tailored consent process for voluntary participation of participants in research including human subjects. There is, however, limited evidence on the design of ethical assessment in studies targeting cancer patients in Ethiopia. REA was conducted to explore factors that influence the informed consent process among female cancer patients recruited for longitudinal research from Addis Ababa Population-based Cancer Registry. Qualitative study employing rapid ethnographic approach was conducted from May–July, 2017, at the Tikur Anbessa Specialized Referral Hospital. In-depth and key informants’ interviews were conducted among purposively selected 16 participants. Regular de-briefings among the study team helped to identify emerging themes and ensure saturation. Interviews and debriefings were tape recorded in Amharic, and transcribed and translated to English. Coding of the transcripts was facilitated by use of NVivo software. Thematic analysis was employed to respond to the initial questions and interpret findings. Perceived barriers to voluntary study participation included lack of reporting back study results of previous studies, the decision making status of women, hopelessness or fatigue in the patients, shyness of the women, data collectors approach to the patient, and patient’s time constraints. Most of the patients preferred oral over written consent and face-to-face interview over telephone interview. Provision of detail information about the study, using short and understandable tool, competent, compassionate and respectful enumerators of the same gender were suggested to assure participation. Due to the perceived severity, the use of the term “cancer” was associated with fear and anxiety. Alternatively, uses of phrases like “breast or cervical illness/disease” were suggested during patient interviews. Voluntary participation is not straight forward but affected by different factors. Using competent, compassionate and respectful enumerators, short and precise questioning tools to limit the time of the interview could improve voluntary participation. Moreover, careful consideration of the patients and families concept of the disease such as wording and information has to be taken into account. This assessment helped in improving the consent process of the ongoing project on breast and cervical cancer patients.

Women infected with Human Immune Deficiency Virus (HIV) are assumed to be at higher risk of developing Cervical Cancer (CC). This is due to a rapid progression of pre-invasive to invasive lesions. However, evidences suggest, due to the availability of antiretroviral therapy (ART) and care services; an improved survival and treatment outcome of CC patients (CCPs) with HIV infection is expected. The aim of this study is to examine the clinical characteristics and survival of of CCPs registered at the radiotherapy center of Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University, Ethiopia. We conducted a retrospective cohort study. Data from 1655 CCPs diagnosed between September 2008 and September 2012 were included. The primary endpoint was death from any cause. Kaplan-Meier estimates were compared using the log-rank test. Cox proportional hazards regression model was used to identify predictors of death. Data were analyzed using STATA version IC/14. The mean age of all patients was 49 years (SD = 11.6 years). Of all CCPs, 139 (8.4%) were HIV positive, 372 (22.5%) patients had a known negative HIV status and 1144 (69.1%) patients were asymptomatic with unknown HIV status. Due to late stage and waiting times, only 13.5% of the patients received curative radiotherapy doses. HIV-positive CCPs presented more often with advanced disease compared to HIV negative CCPs ((44.6%) versus 39.7%, p = 0.007). There was no significant difference in survival between HIV-positive and HIV-negative CCPs. Older age (HR = 2.01; 95% CI, 1.01,-4.05), advanced disease (HR = 2.6; 95% CI, 1.67–4.04) and baseline anemia (HR = 1.65; 95% CI, 1.24, 2.20) were independent predictors for higher risk of death. Survival rates of CCPs did not differ according to HIV status. The risk of death was higher for patients with older age, advanced disease and anemia. HIV patients should be screened for CC according to guidelines to avoid late presentation.

In contrast with breast cancers (BCs) in other parts of the world, most previous studies reported that the majority of BCs in sub-Saharan Africa are estrogen-receptor (ER) negative. However, a recent study using the US SEER database showed that the proportion of ER-negative BC is comparable between US-born blacks and West-African born blacks but substantially lower in East African-born blacks, with over 74% of patients Ethiopians or Eritreans. In this paper, we provide the first report on the proportion of ER-negative BC in Ethiopia, and the relation to progesterone-receptor (PgR) status. We analysed 352 female patients with ER results available out of 1208 consecutive female BC patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. The influences of age, stage, and histology on the probability of ER-negative tumours were assessed by a log-linear regression model. Of the 352 patients, only 35% were ER-negative. The proportion of ER-negative tumours decreased with advancing age at diagnosis and was not affected by histology or stage. For age, the proportion decreased by 6% for each additional 5 years (stage-adjusted prevalence ratio PR = 0.94, 95% CI: 0.89–1.00). About 31% were ER- and PgR-negative, and 69% were ER- and/or PgR-positive. Contrary to most previous reports in other parts of sub-Saharan Africa, the majority of patients in Ethiopia are ER-positive rather than ER-negative. These findings are in line with low proportions of ER-negative BCs from East African immigrants within the SEER database, and they have clinical implications for management of BC patients in Ethiopia and other parts of sub-Saharan Africa where ER-status is not ascertained as part of routine management of the disease. Since the majority of patients showed ER-positive BC, Tamoxifen-therapy should be given to all patients even with unknown ER status.