Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2020-042788 on 7 December 2020. Downloaded from Effectiveness of interventions for improving timely diagnosis of breast and cervical cancers in low and middle- income countries: a systematic review protocol Chukwudi Arnest Nnaji ,1,2 Paul Kuodi ,3 Fiona M Walter ,4 Jennifer Moodley 1,5,6 To cite: Nnaji CA, Kuodi P, ABSTRACT Strengths and limitations of this study Walter FM, et al. Effectiveness Introduction Breast and cervical cancers pose a major of interventions for improving public health burden globally, with disproportionately ► This protocol was designed in accordance with stan- timely diagnosis of breast high incidence, morbidity and mortality in low- and and cervical cancers in dard systematic review protocol guidelines. middle- income countries (LMICs). The majority of low and middle-income ► Literature search will be comprehensive, covering women diagnosed with cancer in LMICs present with countries: a systematic both peer-reviewed and relevant grey literature. late- stage disease, the treatment of which is often review protocol. BMJ Open ► No language restriction will be applied in the search. 2020;10:e042788. doi:10.1136/ costlier and less effective. While interventions to ► It is possible that the review will not include all rele- bmjopen-2020-042788 improve the timely diagnosis of these cancers are vant literature available, as some may not be acces- increasingly being implemented in LMICs, there is ► Prepublication history and sible at the time of review. uncertainty about their role and effectiveness. The additional material for this paper ► The overall strength and applicability of the synthe- is available online. To view these aim of this review is to systematically synthesise sised evidence will depend on the quality of included files, please visit the journal available evidence on the nature and effectiveness of studies. online (http:// dx. doi. org/ 10. interventions for improving timely diagnosis of breast 1136/ bmjopen- 2020- 042788). and cervical cancers in LMICs. Methods and analysis A comprehensive search INTRODUCTION http://bmjopen.bmj.com/ Received 14 July 2020 of published and relevant grey literature will be Revised 08 October 2020 conducted. The following electronic databases will be Breast and cervical cancer constitute a major Accepted 13 November 2020 1 2 searched: MEDLINE (via PubMed), Cochrane Library, public health burden globally. They are Scopus, CINAHL, Web of Science and the International particularly burdensome in low- and middle- Clinical Trials Registry Platform (ICTRP). Evidence income countries (LMICs), where their will be synthesised in accordance with the Preferred incidence, morbidity and mortality are dispro- Reporting Items for Systematic Review and Meta- portionately high.2 3 Breast cancer, the the Analyses (PRISMA). Two reviewers will independently most common cancer among women world- screen the search outputs, select studies using wide, accounts for about 30% of all cancers in on September 30, 2021 by guest. Protected copyright. predefined inclusion criteria and assess each included women in LMICs.4 The majority (53%) of new study for risk of bias. If sufficient data are available and breast cancer cases occur in women living in studies are comparable in terms of interventions and LMICs.5 With an age-standardised incidence outcomes, a meta- analysis will be conducted. Where rate (ASIR) of 31 per 100 000 women, there studies are not comparable and a meta- analysis is not are over half a million new cases every year appropriate, a narrative synthesis of findings will be 4 reported. in LMICs. Cervical cancer represents 16% Ethics and dissemination As this will be a systematic of the total cancer burden in LMICs, with an © Author(s) (or their review of publicly available data, with no primary ASIR of 16 per 100 000 women and an inci- employer(s)) 2020. Re- use 2 data collection, it will not require ethical approval. dence of 300 000 new cases every year. Nine permitted under CC BY-NC. No commercial re- use. See rights Findings will be disseminated widely through a peer- out of every 10 of these cases will likely lead to 2 and permissions. Published by reviewed publication and forums such as conferences, premature death. BMJ. workshops and community engagement sessions. Nearly 70% of all cancer deaths, including For numbered affiliations see This review will provide a user- friendly evidence those due to breast and cervical cancer, end of article. summary for informing further efforts at developing and occur in LMICs.4 Of greater concern is implementing interventions for addressing delays in that the number of new cancer cases, their Correspondence to breast and cervical cancer diagnosis in LMICs. associated morbidity and deaths in LMICs Dr Chukwudi Arnest Nnaji; PROSPERO registration number CRD42020177232. nnjchu001@ myuct. ac. za are expected to grow substantially in the Nnaji CA, et al. BMJ Open 2020;10:e042788. doi:10.1136/bmjopen-2020-042788 1 Open access BMJ Open: first published as 10.1136/bmjopen-2020-042788 on 7 December 2020. Downloaded from coming decades.6 This growth will be due in part to and staging; access to treatment; and follow- up.14 18 population growth, shifts in demographics and expo- The phases are conceptualised based on the Model of sures to known risk factors, in keeping with the epide- Pathways to Treatment framework proposed by Walter, miological transition from communicable diseases to Scott and colleagues, which identifies five key events non- communicable diseases.1 6 While the incidence in the pathway to care: detection of bodily changes; of cancers increases in LMICs, many cases continue perceived reasons to discuss symptoms with a healthcare to go undiagnosed because of a lack of high- quality provider; first consultation with a healthcare provider; population- based registries, and when diagnosed, the diagnosis and start of treatment.24 25 The framework majority present at late- stage with consequently poor also identifies four important intervals between these outcomes.7–9 phases: the appraisal, help seeking, diagnostic and the Breast and cervical cancer mortality and survival are pre- treatment intervals. These events and processes largely influenced by the timeliness of diagnosis and represent particular moments at which barriers may effectiveness of treatment modalities.7 8 10 In many exist and delay patients’ access to care before or after LMICs, breast and cervical screening and early diagnosis a cancer diagnosis.7 26 programmes do exist in some form, however, they tend to be opportunistic and not well organised.11–13 There is often poor access to high quality, affordable breast and STUDY RATIONALE cervical cancer treatment, particularly where the health Interventions aimed at promoting early breast and systems are fragile or fragmented.6 14 In addition to these cervical cancer detection are increasingly being health system factors are the underlying sociocultural and adopted globally, particularly in HICs.21 27 28 Given financial barriers to cancer prevention, diagnosis and the substantial differences between HICs and LMICs treatment services.6 12 15 16 Lay beliefs, such as beliefs that regarding health resources, environment, infrastruc- breast cancers are punitive consequences of sins or a type ture, technology and medical personnel, improving of divine retribution, are held within some communi- time to diagnosis for breast and cervical cancer in ties in LMICs, as are concerns that breast cancer surgery LMIC settings may require different approaches.3 may result in deformity, which may subsequently lead to We have identified two previous reviews on this topic divorce or family abandonment.13 17 As a result of these within the LMIC context.6 8 A scoping review by Dalton issues, women in LMICs with breast and cervical cancers and colleagues synthesised the evidence on patient may be reluctant to seek care following their awareness of navigation strategies for cancer care in LMICs, but symptoms, leading to delays in diagnosis. Consequently, focussed broadly on the entire cancer detection, a high proportion of patients are diagnosed at advanced treatment and care continuum, and not specific to stage, when treatment is often less effective and more breast or cervical cancer.6 The literature search was 12 15 expensive. concluded in December 2018. A systematic review by http://bmjopen.bmj.com/ Evidence suggests that improved timeliness of Qu and colleagues assessed interventions specifically cancer diagnosis is critical for optimising patients’ aimed at addressing barriers to early cancer diagnosis navigation of the pathway from symptom awareness to in LMICs.8 However, it did not specifically focus on treatment and follow- up.18–20 Timely cancer diagnosis breast and cervical cancer, and the literature search can enhance opportunities for treatment with cura- was concluded in November 2017. tive intent.21 However, much of this evidence is from Therefore, our review aims to provide a more up high- income countries (HICs), many of which do not to date, robust and comprehensive synthesis of the have the sociocultural, financial, health system and evidence on the nature and effectiveness of interven- on September 30, 2021 by guest. Protected copyright. knowledge barriers to timely cancer diagnosis and tions for improving timely diagnosis of breast and effective cancer treatment that many LMICs grapple cervical cancer in LMICs. We have focussed on early with.6 8 In an effort to address this evidence gap and diagnosis of symptomatic breast and cervical cancers, provide global standards for early cancer diagnosis, the as the outcome (such as clinical downstaging) is easier WHO published the WHO Guide to Cancer Early Diag- to evaluate, unlike screening in which outcomes may nosis in 2017.22 The guide provides a clear framework be complicated by factors such as the time lag between for cancer control programmes around the world to cervical cancer screening and symptom development, systematically address barriers that may impede timely as well as over- diagnosis of precancerous cervical cancer diagnosis, treatment and care.