Knowledge, Attitude, and Practice of Cervical Cancer Screening and Associated Factors Among Reproductive Aged Women in Ethiopia: A Meta-Analysis and Systematic Review

Background: Cervical cancer is the leading cause of cancer deaths, accounting for 9% of female cancer deaths. In addition, more than 85% of cervical cancer related deaths are found in low and middle-income countries. Women’s knowledge and attitude are barriers for the uptake of cervical cancer screening service in Ethiopia. Studies conducted on knowledge, attitude, and practice of cervical cancer screening and associated factors among reproductive age women are inconsistent. Therefore, this systematic review and meta-analysis aimed to estimate the national level of knowledge, attitude, and practice of cervical cancer screening and associated factors among women aged 15-49 years in Ethiopia. Methods: An international database such as PubMed, EMBASE, Scopus, Google Scholar, Science Direct Cochrane library, and Grey literature databases were searched an extensively. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guideline were pursued for this review. The quality of each study was assessed using Newcastle- Ottawa quality assessment tool. Stata version 14 was used to analyze the data. We have used a random effects model to estimate the pooled prevalence and odds ratio with 95% CI. The possible heterogeneity between studies was assessed using I-squared (I 2 ) test statistic. Egger’s test was used to assess the publication bias. Result: Eighteen studies with a total of 9, 897 women were included in this meta-analysis. The pooled national level of knowledge, attitude and practice towards cervical cancer screening among 15-49 years old aged women in Ethiopia was 40.37% (95% CI: 30.09,50.66), 58.87% (95% CI: 42.69,75.05) and 14.02% (95% CI: 9.67,18.37) respectively. Being uneducated (OR: 3.10, 95% CI: 2.09,4.62), Women who had good knowledge (OR: 5.87, 95% CI: 2.57,13.40), Women who had positive attitude (OR: 4.20, 95% CI: 2.86,6.16) and not being married (OR: 3.34, 95% CI: 1.09,10.22) were the major factors of cervical cancer screening practice. Conclusions and Recommendation: This review showed that the

cancer deaths [4]. According to the World Health Organization 2013 report, eighty-three percent of new cases and more than 85% of related deaths were in low and middle-income countries [5]. In East Africa, the incidence of cervical cancer was 42.7 per 100,000 women, followed by Southern Africa with 31.5 per 100,000 women [6]. In Ethiopia in 2012, an estimated 7095 new cervical cancer cases were diagnosed, and 4732 die annually [4]. Despite the increased prevalence of cervical cancer in developing countries, cervical cancer screening awareness is generally low. Cervical cancer is diagnosed at an advanced stage of the disease. This is because of lack of screening and early detection services. [7,8]. High prevalence of HPV infection, low knowledge and awareness about cervical cancer, having multiple sexual partners, early onset of sexual activity, a history of sexually transmitted diseases (STDs), socioeconomic factors, biological factors (e.g. immune compromisation), poor treatment and supportive care infrastructures about cervical cancer and its screening tests are the contributing factors for the high burden of cervical cancer in Sub Saharan Africa (SSA) [2,9]. In developed countries, a considerable reduction in cervical cancer incidence and deaths achieved by effective screening programs. However, cervical cancer is remaining the major leading cause of morbidity and mortality following breast cancer among women in limited-resource countries, including Ethiopia. This is mainly because of poor systematic screening practice, limited access to health services and labs, no screening programs, limited or non-existent awareness among populations and health workers, limited or no access to diagnostics and laboratories, poor referral and follow up [10]. In Ethiopia, the Federal Minister of Health (FMOH) launches guidelines for cancer control plan which aims to provide an information for healthcare providers, implementing partners and other stakeholders involved in the prevention and control of cervical cancer. The program is aimed to decrease the incidence of cervical cancer by 15% by 2020 [11]. However, still, there is scanty information regarding the knowledge, attitude, and practices of cervical cancer screening. Only 0.6% of eligible women were screened for cervical cancer [2,12]. Cervical cancer screening coverage in developing countries is about (19%), in developed countries (63%) [13]. Despite this fact, there is still a gap in knowledge, attitude, and practice of cervical cancer screening in Ethiopia [14]. Women's knowledge and attitude on cervical cancer determine the uptake of service for screening [15].
In Ethiopia, contradicted studies have been conducted to assess knowledge, attitude, and practice of cervical cancer screening and associated factors among women aged 15-49 years in Ethiopia. The gap is still higher and with abundant discrepancy and inconstancy across regions related to the knowledge, attitude, and practice of cervical cancer screening and associated factors. So that assessing the pooled prevalence of knowledge, attitude, and practice of cervical cancer screening and its associated factors at a national level is essential and will provide a pooled estimation. Therefore, this review aimed to assess knowledge, attitude, and practice of cervical cancer screening and associated factors among women aged 15-49 years in Ethiopia. The ndings of this study will be used for policymakers and program planners who work on the area to promote, plan, implement and evaluate cervical cancer screening services and strategies. The study also will provide baseline information for future researchers.

Study design and setting
A systematic review and meta-analysis were conducted to assess knowledge, attitude, and practice of cervical cancer screening and associated factors among women aged 15-49 years in Ethiopia. Ethiopia is located in the horn of Africa. It is bounded by Eritrea to the north, Djibouti, and Somalia to the east, Sudan and South Sudan to the west, and Kenya to the south [16].

Search Strategies
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline was used to con rm the scienti c accuracy [17]. We searched articles without any limit to the date of publication and study design from the major databases such as PubMed/MEDLINE, Web of Science, EMBASE, CINAHL, Google Scholar, Science Direct and Cochrane Library. EndNote (version X7) reference management software was used to download, organize, review and cite the articles. This review included all articles published in peer-reviewed journals, that were written in the English language. [18]. Also, Gray literature of observational studies and o cial websites of international and local organizations and universities were searched. The search of the literature was conducted from the 1st of September, 2019 to the 1st of December, 2019. All papers published until the 1st of December, 2019 were considered. The Electronic databases were searched by medical subject headings (MeSH) terms and using the following keywords: "Knowledge", "Attitude", "Practice", "cervical cancer", "and 15-49 years old women", "barriers", "determinants", "associated factors and Ethiopia". We used the search terms independently and/or in combination using Boolean operators like "OR" or "AND".

Eligibility Criteria
Inclusion criteria Study area Studies conducted only in Ethiopia were considered.

Population
Only studies involving reproductive age women (15-49 years old women) were included.

Publication condition
Both published and unpublished articles were included.

Study design
All observational study designs (i.e., cross-sectional) reporting the knowledge, attitude, and practice of screening cervical cancer among reproductive age groups of women were included.

Language
Articles reported only in English language were considered.

Exclusion criteria
Articles, which were not fully accessible and not reported the outcome of interest, after at least two-email contact with the primary authors, were excluded.

Measurement of outcome variables
The main outcome of this study was to assess the pooled levels of knowledge, Knowledge, Attitude, and Practice of Cervical Cancer Screening and Associated Factors.

Data Extraction And Quality Assessment
Data were extracted using a standardized data extraction spreadsheet format in Microsoft Excel. The data abstraction format includes author/s name, year of publication, study region, study design, sample size, the prevalence of knowledge, prevalence of attitude and prevalence of cervical cancer practice. All published and unpublished primary studies in the English language, conducted at the community or health institution level from 2015 to December 2019 were included. The data were extracted by three independent authors (YM, AAS, and AA). Joanna Briggs Institute (JBI's) critical appraisal checklist for prevalence studies was used to assess the quality of included studies [19]. Additionally, a modi ed version of the Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of studies for cross-sectional studies [20]. Newcastle -Ottawa scale criteria include representativeness of the sample, response rate, measurement tool used, comparability of the subject, appropriateness of the statistical test used to analyze the data. Based on the Newcastle -Ottawa scale criteria, two authors (YM and AA) independently assessed the quality of each article. Whenever necessary, another reviewer (AAS) was involved and any discrepancy was resolved through discussion and consensus.

Data Processing And Analysis
For farther analysis, we imported the data to STATA version 14.0 statistical software after extracting the data using Microsoft Excel format. We identify the heterogeneity between the studies using Cochrane's Q statistics (Chi-square), inverse variance (I 2 ) and p-values [21]. As the test statistic showed there is signi cant heterogeneity among the studies ( Fig. 2A, 2B and 2C) as a result a random-effects metaanalysis model was used to estimate the DerSimonian and Laird's pooled effect. In the current meta-analysis, arcsine-transformed proportions were used. The pooled proportion was estimated by using the back-transform of the weighted mean of the transformed proportions, using arcsine variance weights for the xed-effects model and DerSimonian-Laird weights for the random-effects model [22]. Egger's and Begg's tests, with the p-value, less than 5% was used to declare the presence of publication bias [23]. Also, using forest plot, point prevalence, as well as 95% con dence intervals, was presented. In this plot, the size of each box indicated the weight of the study, while each crossed line refers to a 95% con dence interval. For the second outcome, a log odds ratio was used to determine the association between determinant factors and cervical cancer screening among 15-49 years old women.

Study Selection And Data Extraction
This systematic review and meta-analysis have been reported by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement [24]. Initially, 455 articles related to KAP of cervical cancer screening were found. Of these, 168 duplications and 263 unrelated articles were excluded. Second, from the remaining 24 potential articles, 18 met eligibility for the review and included in the analysis. Six full-text articles were excluded due to did not meet outcomes of interest or study area ( Fig. 1).

Characteristics of included studies
Eighteen studies with a total sample of 9, 897 women (aged 15-49 years old) were included in this systematic review and meta-analysis. The main characteristics of the included studies are described in Table 1.  (Fig. 2B). The pooled prevalence of cervical cancer screening practice among 15-49 years old women in Ethiopia was 14.02% (95% CI: 9.67-18.37). The lowest was (2.10%) and the highest was (40.10%) (Fig. 2C).

Heterogeneity And Publication Bias
The presence of publication bias was examined using visual inspection of the funnel plot and Egger's test. Visual inspection of the funnel plot suggested asymmetrical distribution of included studies. We also observed publication bias in practice of cervical cancer screening using both Begg's and Egger's tests [25,26] and these tests showed that there was statistical evidence of publication bias at p-value less than 0.05 and the funnel plot was asymmetry. By consideration of publication bias trim and ll metaanalysis [31] were done. However, based on this analysis no signi cant change was shown as compared with the main meta-analysis. Moreover, the result of sensitivity analyses using the random-effects model suggested that none of the studies included in uence the overall estimate. Given that the result of this meta-analysis revealed statistically signi cant heterogeneity among studies, we performed a subgroup analysis by region to adjust and minimize heterogeneity (Fig. 3).

Meta-regression
Besides subgroup analysis and publication bias, univariate and categorical meta-regression analysis was performed undertaken by considering both continuous and categorical data for the included studies to identify sources of for heterogeneity for the pooled prevalence. In meta-regression analysis, Sample size, publication year and study regions were considered for each study. However, there was no statistical signi cance value from the meta-regression analysis ( Table 2). The associated factor of the utilization of screening cervical cancer among reproductive age groups in Ethiopia In this meta-analysis, the association between the practice of screening cervical cancer and the educational status of women had been seen using eight studies conducted in Ethiopia. The Mataanalysis of these eight studies revealed that the practice of screening cervical cancer among reproductive-age women was signi cantly associated with the educational status of women (OR: 3.10, 95% CI: 2.09-4.62). Speci cally, the likelihood of cervical cancer screening practice was 3.10 times higher among literate women compared to their counterparts. The test result of this meta-analysis revealed a signi cant heterogeneity among eight studies (I 2 = 78.0%, P ≤ 0.001). So the random effect meta-analysis model was used to see the association educational status with cervical cancer practice in Ethiopia (Fig. 3A). In this meta-analysis, women who had good Knowledge status about cervical cancer was found to be signi cantly associated with cervical cancer screening practice (OR: 5.87, 95% CI: 2.57-13.40). Reproductive age women who had good knowledge about cervical cancer screening were around six times more likely to practice cervical cancer screening compared to those women who did not hear about Cervical cancer screening (Fig. 3B). In this meta-analysis, the association between the practice of screening cervical cancer and women who had a positive attitude towards cervical cancer screening had been seen using six studies conducted in Ethiopia. The Mata-analysis of these six studies revealed that the practice of screening cervical cancer among reproductive-age women was signi cantly associated with women who had a positive attitude towards cervical cancer screening (OR: 4.20, 95% CI: 2.86-6.16) (Fig. 3C). This review revealed that the practice of screening cervical cancer among reproductive-age women was signi cantly associated with women who not being married (OR: 3.34, 95% CI: 1.09-10.22) (Fig. 3D).

Discussion
In Ethiopia, FMOH launches guidelines for cancer control plan which aims to provide healthcare providers, implementing partners and other stakeholders involved in the prevention and control of cervical cancer incidence and mortality by 15% by 2020 [11]. Despite this fact, there is still a gap in knowledge, attitude, and practice of cervical cancer screening in Ethiopia [14]. To our knowledge, this systematic review and meta-analysis are the rst to estimate the pooled level of knowledge, attitude, and practice of cervical cancer screening among15-49 years old aged women in Ethiopia. As a result, this meta-analysis was intended to estimate the pooled level of knowledge, attitude, and practice of cervical cancer screening among15-49 years old aged women in Ethiopia. Besides, we have also seen the determinant factors affecting the practice of cervical cancer screening. The nding of this systematic review and meta-analysis showed that the pooled level of knowledge, attitude and practice towards cervical cancer screening among 15-49 years old aged women in Ethiopia was 40.37% (95% CI: 30.09-50.66), 58.87% (95% CI: 42.69-75.05) and 14.02% (95% CI: 9.67-18.37) respectively ( Fig. 2A, 2B and 2C). Educational status of women, knowledge status about cervical cancer, attitude towards cervical cancer women who heard about Cervical cancer and marital status of women were signi cantly associated with the practice of cervical cancer screening. The KAP towards cervical cancer screening in Ethiopia was lower compared to the other sub-Sahara African countries such as Republic of Congo (81.9%) and in Botswana (77%), and in China (70.2%) [27][28][29] in awareness, in Chinese (80.8%) [29], in South Africa 64.0% [30] in Knowledge and Kenya 22% [31], in Tanzania 14% [32], in Malaysia 6% [33], in Tanzania (22.6%) [34], in Qatar 40% [35], in India, 85% [36] in practice of cervical cancer screening. But it was higher the study done in Nigeria 26.85% [37]. This variation might be justi ed by the extent of the studies and differences in the health service, socio-demographic characteristics of study participants and setting and study period. The educational status of women was also found to be a signi cant predictor for cervical cancer screening practice. Speci cally, literate women were around three times more likely to practice cervical cancer screening compared to their counterparts. This systematic review and meta-analysis were supported by ndings of other studies conducted in Qatar [35], India [38] Congo [28]. These studies acknowledged that maternal education was a signi cant predictor of cervical cancer screening practice, in which women with higher educational levels will be more conscious of the importance of cervical cancer screening. In this meta-analysis, women who had good Knowledge status about cervical cancer was found to be signi cantly associated with cervical cancer screening practice. Reproductive age women who heard about Cervical cancer were around six times more likely to practice cervical cancer screening compared to those women who did not hear about Cervical cancer screening. This review was supported by ndings of other studies conducted in by LAO PDR study [39], in Thailand 81.8% [40] . This review revealed that the practice of screening cervical cancer among reproductive-age women was signi cantly associated with women who not being married. Our ndings have supported by a study done in Malaysia [33]. The possible explanation could be explained as single women are more likely to be younger and more exposed to sexual education and women who were single had a greater knowledge of cervical cancer screening than those who were married.
Additionally, a positive attitude was a signi cant predictor for cervical cancer screening practice. This review ndings was inconsistence with the studies done in India 83.8% [45], in Iran 96.5% [41], Kuwaiti 30.6% [42]. The variation may be due to study population, knowledge and educational status, availability and expansion of alternative information sources, advocacy and promotion activities of cervical cancer screening by health care providers may be better or initiated earlier and socio-economic difference.

Limitations Of The Study
One of the limitations of this systematic review and meta-analysis was only studies written by the English language were included for the pooled estimate.

Conclusions And Recommendation
This review showed that the level of knowledge, attitude, and practice of cervical cancer screening among reproductive-age women in Ethiopia was relatively lower as compared to those reported by other studies done in different countries. Educational status, knowledge, attitude and marital status were statistically signi cant predictors for cervical cancer screening practice among reproductive-age women in Ethiopia. Hence, the health care provider needs to scale up health education and awareness creation about cervical cancer screening and early detection and prevention of cervical cancer. Availability of data and material The datasets analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests
We have con rmed that we have no competing interests. Subgroup Analysis of knowledge about cervical cancer screening in Ethiopia, 2019.