Digital Health Strategies for Cervical Cancer Control in Low- and Middle-Income Countries: Systematic Review of Current Implementations and Gaps in Research

Background:
Nearly 90% of deaths due to cervical cancer occur in low- and middle-income countries (LMICs). In recent years, many digital health strategies have been implemented in LMICs to ameliorate patient-, provider-, and health system–level challenges in cervical cancer control. However, there are limited efforts to systematically review the effectiveness and current landscape of digital health strategies for cervical cancer control in LMICs.

Objective:
We aim to conduct a systematic review of digital health strategies for cervical cancer control in LMICs to assess their effectiveness, describe the range of strategies used, and summarize challenges in their implementation.

Methods:
A systematic search was conducted to identify publications describing digital health strategies for cervical cancer control in LMICs from 5 academic databases and Google Scholar. The review excluded digital strategies associated with improving vaccination coverage against human papillomavirus. Titles and abstracts were screened, and full texts were reviewed for eligibility. A structured data extraction template was used to summarize the information from the included studies. The risk of bias and data reporting guidelines for mobile health were assessed for each study. A meta-analysis of effectiveness was planned along with a narrative review of digital health strategies, implementation challenges, and opportunities for future research.

Results:
In the 27 included studies, interventions for cervical cancer control focused on secondary prevention (ie, screening and treatment of precancerous lesions) and digital health strategies to facilitate patient education, digital cervicography, health worker training, and data quality. Most of the included studies were conducted in sub-Saharan Africa, with fewer studies in other LMIC settings in Asia or South America. A low risk of bias was found in 2 studies, and a moderate risk of bias was found in 4 studies, while the remaining 21 studies had a high risk of bias. A meta-analysis of effectiveness was not conducted because of insufficient studies with robust study designs and matched outcomes or interventions.

Conclusions:
Current evidence on the effectiveness of digital health strategies for cervical cancer control is limited and, in most cases, is associated with a high risk of bias. Further studies are recommended to expand the investigation of digital health strategies for cervical cancer using robust study designs, explore other LMIC settings with a high burden of cervical cancer (eg, South America), and test a greater diversity of digital strategies.

Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia

Expedited diagnostic processes for all suspected cervical cancer cases remain essential in the effort to improve clinical outcomes of the disease. However, in some developing countries like Zambia, there is paucity of data that assesses factors influencing diagnostic and treatment turnaround time (TAT) and other metrics vital for quality cancer care. We conducted a retrospective hospital-based study at the Cancer Diseases Hospital (CDH) for cervical cancer cases presenting to the facility between January 2014 and December 2018. Descriptive statistics were used to summarize demographic characteristics while a generalized linear model of the negative binomial was used to assess determinants of overall TAT. Our study included 2121 patient case files. The median age was 49 years (IQR: ±17) and most patients (n=634, 31%) were aged between 41–50 years. The International Federation of Gynaecology and Obstetrics (FIGO) Cancer stage II (n =941, 48%) was the most prevalent while stage IV (n=103, 5.2%) was the least. The average diagnostic TAT in public laboratories was 1.48 (95%CI: 1.21–1.81) times longer than in private laboratories. Furthermore, referral delay was 55 days (IQR: 24–152) and the overall TAT (oTAT) was 110 days (IQR: 62–204). The age of the patient, HIV status, stage of cancer and histological subtype did not influence oTAT while marital status influenced oTAT. The observed longer oTAT may increase irreversible adverse health outcomes among cervical cancer patients. There is a need to improve cancer care in Zambia through improved health expenditure especially in public health facilities.

Burden of Cervical Cancer in the Eastern Mediterranean Region During the Years 2000 and 2017: Retrospective Data Analysis of the Global Burden of Disease Study

Background:
Cervical cancer is a growing health concern, especially in resource-limited settings.

Objective:
The objective of this study was to assess the burden of cervical cancer mortality and disability-adjusted life years (DALYs) in the Eastern Mediterranean Region (EMR) and globally between the years 2000 and 2017 by using a pooled data analysis approach.

Methods:
We used an ecological approach at the country level. This included extracting data from publicly available databases and linking them together in the following 3 steps: (1) extraction of data from the Global Burden of Disease (GBD) study in the years 2000 and 2017, (2) categorization of EMR countries according to the World Bank gross domestic product per capita, and (3) linking age-specific population data from the Population Statistics Division of the United Nations (20-29 years, 30-49 years, and >50 years) and GBD’s data with gross national income per capita and globally extracted data, including cervical cancer mortality and DALY numbers and rates per country. The cervical cancer mortality rate was provided by the GBD study using the following formula: number of cervical cancer deaths × 100,000/female population in the respective age group.

Results:
The absolute number of deaths due to cervical cancer increased from the year 2000 (n=6326) to the year 2017 (n=8537) in the EMR; however, the mortality rate due to this disease decreased from the year 2000 (2.7 per 100,000) to the year 2017 (2.5 per 100,000). According to age-specific data, the age group ≥50 years showed the highest mortality rate in both EMR countries and globally, and the age group of 20-29 years showed the lowest mortality rate both globally and in the EMR countries. Further, the rates of cervical cancer DALYs in the EMR were lower compared to the global rates (2.7 vs 6.8 in 2000 and 2.5 vs 6.8 in 2017 for mortality rate per 100,000; 95.8 vs 222.2 in 2000 and 86.3 vs 211.8 in 2017 for DALY rate per 100,000; respectively). However, the relative difference in the number of DALYs due to cervical cancer between the year 2000 and year 2017 in the EMR was higher than that reported globally (34.9 vs 24.0 for the number of deaths and 23.5 vs 18.1 for the number of DALYs, respectively).

Conclusions:
We found an increase in the burden of cervical cancer in the EMR as per the data on the absolute number of deaths and DALYs. Further, we found that the health care system has an increased number of cases to deal with, despite the decrease in the absolute number of deaths and DALYs. Cervical cancer is preventable if human papilloma vaccination is taken and early screening is performed. Therefore, we recommend identifying effective vaccination programs and interventions to reduce the burden of this disease.

Predictors of Five-Year Overall Survival in Women Treated for Cervical Cancer at the Kenyatta National Hospital in 2008

Cervical cancer is the fourth most commonly diagnosed and the fourth leading cause of cancer death among women worldwide. In many low- and middle-income countries (LMICs) including Kenya cervical cancer remains the leading cause of cancer death among women. This situation is due to the fact that despite the existence of effective preventive and early detection programs, lack of implementation in LMICs leads many women suffering from the disease to premature death. This study was aimed at estimating the five-year overall survival rates for women with cervical cancer in Kenya. To achieve this, the study employed a retrospective cohort design where medical records of all patients who commenced treatment for cervical cancer in 2008 were reviewed retrospectively over a period of five years from 2008- 2013. Data analysis involved the use of Stata v14.2 to generate descriptive statistics and conduct survival analysis. The five-year overall survival estimate for women with cervical cancer at Kenyatta National Hospital (KNH) in 2008 was found to be 59%. Stage of disease at diagnosis, type of treatment received and whether or not treatment was initiated and completed are the three factors revealed to have the strongest influence on patient survival. Occupation which was used as a proxy for socio-economic status (SES) did not reflect the financial burden imposed on patients seeking treatment. However, the loss to follow up was significantly high at a rate of 82.3%; with no deaths observed after the first year, the overall survival estimate is only accurate over the first year. The results of this study provided insight on the relationship between various socio-demographic and clinical factors and patient outcomes of cervical cancer treatments at KNH. Moreover, it highlighted the ongoing health system challenges surrounding provision of and access to cancer treatment. The results will inform policy makers and health service providers on the quality and accessibility of available cervical cancer treatments as delivered within our healthcare setting

Cervical cancer in Sub‐Saharan Africa: a multinational population‐based cohort study on patterns and guideline adherence of care

Abstract
Background
Cervical cancer (CC) is the most common female cancer in many countries of sub‐Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS).

Methods
Our observational study covered nine population‐based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44‐125 patients diagnosed 2010‐2016 were selected in each. Cancer‐directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (USA) Guidelines.

Results
Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline‐adherent, 2.4% with minor and 8.2% major deviations. CDT was not documented or without curative potential in 22%; 15.7% were diagnosed FIGO IV disease. Adherence was not assessed in 46.9% (no stage or follow‐up documented 11.9%) or records not traced (35.1%). The largest share of guideline‐adherent CDT was observed in Nairobi (49%), the smallest in Maputo (4%). In FIGO I‐III patients (n=190), minor and major guideline deviations were associated with impaired OS: hazard rate ratio (HRR) 1.73, 95% confidence interval (CI) 0.36‐8.37; and HRR 1.97, CI 0.59‐6.56 respectively. CDT without curative potential (HRR 3.88, CI 1.19‐12.71) and no CDT (HRR 9.43, CI 3.03‐29.33) showed substantially worse survival.

Conclusion
We found only one in six cervical cancer patients in SSA received CDT with curative potential. At least one‐fifth and possibly up to two thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of man

Working title: high dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience

Background and purpose
Cervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes.

Methods
A retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity.

Results
A total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae.

Conclusion
One hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.

Surgical candidacy and treatment initiation among women with cervical cancer at public referral hospitals in Kampala, Uganda: a descriptive cohort study

Objectives This study aimed to report the proportion of women with a new diagnosis of cervical cancer recommended for curative hysterectomy as well as associated factors. We also report recommended treatments by stage and patterns of treatment initiation.

Design This was an observational cohort study. Inperson surveys were followed by a phone call.

Setting Participants were recruited at the two public tertiary care referral hospitals in Kampala, Uganda.

Participants Adult women with a new diagnosis of cervical cancer were eligible: 332 were invited to participate, 268 met the criteria and enrolled, and 255 completed both surveys.

Primary and secondary outcomes measures The primary outcome of interest was surgical candidacy; a secondary outcome was treatment initiation. Descriptive and multivariate statistical analyses examined the associations between predictors and outcomes. Sensitivity analyses were performed to examine outcomes in subgroups, including stage and availability of radiation.

Results Among 268 participants, 76% were diagnosed at an advanced stage (IIB–IVB). In total, 12% were recommended for hysterectomy. In adjusted analysis, living within 15 km of Kampala (OR 3.10, 95% CI 1.20 to 8.03) and prior screening (OR 2.89, 95% CI 1.22 to 6.83) were significantly associated with surgical candidacy. Radiotherapy availability was not significantly associated with treatment recommendations for early-stage disease (IA–IIA), but was associated with recommended treatment modality (chemoradiation vs primary chemotherapy) for locally advanced stage (IIB–IIIB). Most (67%) had started treatment. No demographic or health factor, treatment recommendation, or radiation availability was associated with treatment initiation. Among those recommended for hysterectomy, 55% underwent surgery. Among those who had initiated treatment, 82% started the modality that was recommended.

Conclusion Women presented to public referral centres in Kampala with mostly advanced-stage cervical cancer and few were recommended for surgery. Most were able to initiate treatment. Lack of access to radiation did not significantly increase the proportion of early-stage cancers recommended for hysterectomy.

Designing for Health Accessibility: Case Studies of Human-Centered Design to Improve Access to Cervical Cancer Screening

Our world faces immense challenges in global health and equity. There continue to be huge disparities in access to health care across geographies, despite the massive strides that have been made to address health issues. In this dissertation, I explore the role of human-centered design to improve global health access and reduce disparities. Human-centered design, a cross-disciplinary creative problem-solving approach, has been applied and studied in both academic research and practice, but its role in improving global health access remains poorly understood.

In this dissertation, I present research on designing for health accessibility in the context of one particular disease: cervical cancer. Every year, 300,000 women around the world die of cervical cancer and ninety percent of these deaths occur in low- and middle-income countries. Cervical cancer is an illustrative example of the global disparities in access to health care, given that cervical cancer is preventable and the majority of global cervical cancer mortality is in low- and middle-income countries.

My research examines the work of two organizations that created unique solutions to improve access to cervical cancer screening in India and Nicaragua. I develop case studies of each organization grounded in ethnographic fieldwork, including over 250 hours of observation and 15 interviews over two years. Through these case studies, I show how early efforts to understand the barriers inhibiting cervical cancer screening access allow design practitioners to create novel and feasible ways to address these barriers. This demonstrates the importance of design practitioners considering multiple dimensions of accessibility, including availability, physical accessibility, accommodation, affordability, and acceptability, while conducting design research in order to improve the potential impact of their ideas and prototypes. Overall, this dissertation establishes the foundation of a new paradigm to “design for accessibility” that can inspire further application and research across sectors to address the many social equity and accessibility challenges facing our world.

Factors Associated with Loss to Follow-up among Cervical Cancer Patients in Rwanda

Background:
Cervical cancer is among the most common cancers affecting women globally. Where treatment is available in low- and middle-income countries, many women become lost to follow-up (LTFU) at various points of care.

Objective:
This study assessed predictors of LTFU among cervical cancer patients in rural Rwanda.

Methods:
We conducted a retrospective study of cervical cancer patients enrolled at Butaro Cancer Center of Excellence (BCCOE) between 2012 and 2017 who were either alive and in care or LTFU at 12 months after enrollment. Patients are considered early LTFU if they did not return to clinic after the first visit and late LTFU if they did not return to clinic after the second visit. We conducted two multivariable logistic regressions to determine predictors of early and late LTFU.

Findings:
Of 652 patients in the program, 312 women met inclusion criteria, of whom 47 (15.1%) were early LTFU, 78 (25.0%) were late LTFU and 187 (59.9%) were alive and in care. In adjusted analyses, patients with no documented disease stage at presentation were more likely to be early LTFU vs. patients with stage 1 and 2 when controlling for other factors (aOR: 14.93, 95% CI 6.12–36.43). Patients who travel long distances (aOR: 2.25, 95% CI 1.11, 4.53), with palliative care as type of treatment received (aOR: 6.65, CI 2.28, 19.40) and patients with missing treatment (aOR: 7.99, CI 3.56, 17.97) were more likely to be late LTFU when controlling for other factors. Patients with ECOG status of 2 and higher were less likely to be late LTFU (aOR: 0.26, 95% CI 0.08, 0.85).

Conclusion:
Different factors were associated with early and later LTFU. Enhanced patient education, mechanisms to facilitate diagnosis at early stages of disease, and strategies that improve patient tracking and follow-up may reduce LTFU and improve patient retention.

Surgical management of cervical cancer in a resource‐limited setting: One year of data from the National Cancer Institute, Sri Lanka

Objective
To evaluate the surgical management of cervical cancer without the use of preoperative pelvic imaging in a resource‐limited setting.

Methods
A retrospective study was carried out using clinical records and the ongoing electronic database at the Gynaecological Oncology Unit, National Cancer Institute (Apeksha Hospital), Maharagama, Sri Lanka. Details regarding the radical hysterectomies carried out from January 1, 2019, to December 31, 2019, were retrospectively studied.

Results
Out of nearly 700 patients with cervical cancer admitted during the year 2019, 57 surgically managed radical hysterectomies were included. Of these, seven cases were ineligible and excluded and 50 cases of radical hysterectomies were included for analysis. Mean age was 53.6 ± 9.5 years and median parity was 3 (range 2–4). Of the cases, 94% were found to have no parametrial involvement showing the success of clinical examination in assessing local tumor spread. Overall, 11 (22.0%) were upstaged due to lymph node metastasis that was statistically significant.

Conclusion
Preoperative clinical staging is a practical method in selecting surgically treatable cervical cancer in low‐ and middle‐income countries (LMICs). Combining clinical assessment with comparatively more readily available computed tomography scans could be helpful in triaging patients for treatment of cervical cancer in LMICs.