This was an ecological study that was conducted at the country level. Three publicly available databases were linked together in a three-step process. The first step consisted of extracting cervical cancer data at the country level from the Global Burden of Disease (GBD) study in 2000 and 2017 [13] to provide the numbers and rates of cervical cancer mortality as well as the numbers and rates of DALYs. We chose the data from the years 2000 and 2017 as the most recent data available from the cancer registry system.

The EMR consists of the following 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iraq, Iran, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine (West Bank and Gaza), Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, and the United Arab Emirates [14]. The cervical cancer mortality of 122 countries was expressed as the overall mortality and DALYs (number and rates) in the GBD study. As the countries vary significantly in terms of their levels of economic development, they were stratified, in the second step, to 3 standard world economy groups according to the World Bank definition based on the gross national income per capita in 2017: HICs at >US $12,056, MICs at US $996-12,055, and low-income countries (LICs) at <US $995 [14]. The LICs are Afghanistan and Somalia. The MICs are Djibouti, Egypt, Iraq, Iran, Jordan, Lebanon, Libya, Morocco, Pakistan, Palestine (West Bank and Gaza), Sudan, Syria, Yemen, and Tunisia. The HICs are Bahrain, Saudi Arabia, Kuwait, Oman, Qatar, and the United Arab Emirates [14]. The third step included extracting age-specific population data (rate and frequency) from the Population Statistics Division of the United Nations [15]. This was necessary as the GBD study data were different from those of the Population Statistics Division and they provide no rates at regional or income level.

Cervical cancer mortality rates and DALY rates per 100,000 persons were extracted from the GBD database for people older than 20 years at the country level in the years 2000 and 2017 and then combined for an EMR average (n=22) and global average of EMR plus all other countries (n=122). The mortality rate formula was as follows: cervical cancer deaths (n) × 100,000/female population in the respective age group. The results were then stratified by the 3 income levels (high, middle, low) and 3 age groups (20-29 years, 30-49 years, ≥50 years). The burden of cervical cancer mortality was presented through the compilation of 3 variables: (1) average mortality rates per 100,000 with minimum and maximum values to provide the range as a measure of spread for cervical cancer mortality and mortality from other diseases, (2) DALYs as a measure of total burden, whereby 1 DALY represents 1 healthy year of life lost to cervical cancer; the GBD study did estimate DALYs by summing the fatal burden (years of life lost) and nonfatal burden (years of life with disability) due to cervical cancer [16], and (3) relative difference (%) and absolute difference between years 2000 and 2017 to show the comparative changes in deaths and DALY numbers. The absolute difference equals the difference between the 2 comparing numbers of years 2000 and 2017. The relative difference is equal to the value of the absolute difference divided by the value in the year 2000, and then we multiplied it by 100 [17].

In this study, we report the results of the data analysis on both mortality and DALYs associated with cervical cancer in 22 countries in the EMR. We found a change in the number of deaths and mortality rates from the year 2000 to the year 2017. Although the number of deaths due to cervical cancer has increased in the year 2017 (n=8537) compared to that in the year 2000 (n=6326) in the EMR, the mortality rate decreased in 2017 (2.5 per 100,000) compared to that in 2000 (2.7 per 100,000). The population expansion in the younger age groups may have contributed to the reduction in the mortality rates. For example, the population size in EMR-LICs in 2017 increased two-fold in comparison to that in the year 2000. According to the causation and nature of cervical cancer, there exists 10-20 years of gap between HPV infection and the development of cervical cancer. Thus, this disease is not seen in the younger generation; therefore, population expansion does not affect the number of deaths whereas mortality rate calculation under its influence decreases, as reported in previous studies [18]. Previous studies have shown that mortality rates and DALY rates are low in Saudi Arabia and Iran [18,19]; therefore, 1 study suggested that the cost-effectiveness of investment on HPV vaccination should be examined and if the incidence of cervical cancer is truly low, there is no reason for public health to institute either screening or vaccination [20].

Our results showed that large differences existed within the EMR in both deaths and DALYs. Considering the stratification by country income level, we found that HICs carried the largest burden of deaths and the number burden of DALYs for the 2 reference years (85.5%) compared to MICs and LICs (34.2% and 33.3%, respectively) and for all the 3 age groups (25.6%, 110%, and 74.8% vs 13.5%, 27.4%, and 39% vs 12.8%, 49.6%, and 25.1%, respectively). The EMR-HICs, unlike the HICs globally, may have higher relative difference even in comparison to LICs. This might have different causes apart from their economic level that are common in countries of the EMR.

In our study, we consider that one cause that may be relevant is the economic development of the Gulf region in the last 3 decades. This development may have improved the access to health care services, education, and changes in lifestyle and nutrition and traditional social and family structures [11]. For example, marriage in some areas includes the practice of either polygamy or temporary marriage, known by the names of “mesiar and mesfar”; this may contribute to the increase in the prevalence of HPV infections [21]. The first notable factor in this region is the lack of a reliable system of registry for diseases, including cervical cancer. According to the World Health Organization (WHO) cancer country profiles, Afghanistan [22], Somalia [23], Djibouti [24], Libya [25], and Pakistan [26] do not have a cancer registry. As per the WHO, the situation of cervical cancer in EMR should be assessed and improved [1]. The WHO’s first step is related to primary prevention through immunization against HPV of all 9-13-year-old girls before their sexual debut. HPV in almost all of the cases is the main attributable risk factor for cervical cancer, and the risk of developing cervical cancer is highly associated with the age of first intercourse; the younger the individual, the more is the probability of developing infection into papillomavirus-associated cancer [27]. All the countries in the EMR report the prevalence of HPV strains 16 and 18 (the most oncogenic subtypes of HPV) in women with normal cytology—from 0.2% in Kuwait [28] up to 4.8% in Somalia [29] and Djibouti [30], which has the potential to progress to cervical precancer and cancer in 10-20 years. The prevalence of HPV strains 16 and 18 in low-grade lesions was from 20.8% in Morocco [31] and Libya [32] up to 42.9% in Iran [33] and that in high-grade lesions was from 45.7% in Somalia [29] and Djibouti [30] up to 63.4% in Afghanistan [34] and Pakistan [35]. In women with cervical cancer, the prevalence was from 58.6% in Iran [33] up to 92.7% in Jordan [36]. This shows the importance of HPV vaccination in these countries to ensure that the infection does not progress to cervical precancer and cancer. Among the EMR countries, Libya [31] has had a national HPV vaccination program since 2013, and Emirates [37] had a partial program since 2008. In addition, in the EMR, education and knowledge on cervical cancer are reported as important determinative factors in primary prevention [38]. The increased education of women and their families about cervical cancer, its causes, signs, symptoms, and preventions will engage them more in the preventive and screening practices [38]. The WHO’s other primary preventive measures are “Girls and boys, as appropriate—Health information and warnings about tobacco use—Sexuality education tailored to age and culture—Condom promotion/provision for those engaged in sexual activity—Male circumcision” [1]. Almost all of the countries of the EMR report more than 80% male circumcision, and the usage of condom is low from 0.0% in Somalia [29] and Sudan [39] up to 13.8% in Iran [33]. With regard to the sexual education for girls and boys, a study conducted in Iran generalized the matter to all Muslim countries and reported the social unacceptability of sexual health education for unmarried people due to religious and cultural prohibition of extramarital sex, in particular, for girls. Further, sexual education highlights the effect of technology improvement and internet on the sexual behaviors of youth, including extramarital relationships, and this should not be denied [40]. The WHO’s second step to comprehensive prevention and control of cervical cancer is related to secondary prevention through effective screening of women older than 30 years and treatment as needed with low-cost technology, for example, visual inspection with acetic acid (VIA) followed by cryotherapy [1]. In the EMR, Somalia [29], Djibouti [30], Libya [32], Sudan [39], and Yemen [41] have no cervical cancer screening programs. Two countries, Tunisia [42] and Morocco [31], have quality assurance structures, which supervise and monitor the screening; however, none of them has an active invitation for screening. In Egypt, the cost of screening and treatment is not covered by public funding; therefore, this is considered as a nonaffordable service by over 40% of the Egyptian women [43]. Cytology is considered as the main screening test in EMR, except for Morocco [31] and Pakistan [35] where VIA is used. The VIA is suggested especially in LICs and rural areas that do not have access to health care facilities [44]. Further, women face additional challenges such as language, transportation, insurance, and family pressure as inhibitors for obtaining regular cervical cancer screening, especially in case it is perceived as a threat to their cultural and religious values [45]. The reported barriers in the rural areas are the financial costs, acceptance by husbands, and availability of a female health care provider [43].

The early detection of cancer reduces financial burdens, both on the health care system and economically [46]. Screening and vaccination programs are considered to be more accessible and effective than relying only on cancer treatment. For example, in Saudi Arabia, the pap test is fully subsidized in public hospitals, and it costs US $50 in private clinics. Yet, these costs are negligible compared to the costs of cervical cancer treatment, where it can vary between US $14,000-US $30,000 during the first year of therapy [21].

The WHO recommends a comprehensive prevention and control of cervical cancer, which is related to tertiary prevention for women older than 30 years. This includes treating invasive cancer at any age, including ablative surgery, radiotherapy, and chemotherapy palliative care [1]. However, radiotherapy is not generally available in Afghanistan [22], Somalia [23], Djibouti [24], Egypt [47], and Pakistan [26] and is generally available in other countries of the EMR. The availability of radiotherapy centers ranges from 1 center in Yemen [48], Bahrain [49], Kuwait [50], Oman [51], and Qatar [52] up to 40 centers in Iran [53]. The availability of radiation clinics ranges from 3 centers in Qatar [52] up to 237 centers in Egypt [47]. Chemotherapy is not available in Afghanistan [22], Somalia [23], Djibouti [24], Egypt [47], and Pakistan [26], but it is available in other countries of the EMR. Finally, community/home care for people with advanced-stage cancer is only available in 2 countries of the EMR, namely, Bahrain [49] and Kuwait [50].

The ongoing civil unrest may have affected the quality of the health data in the EMR, as the GBD study uses modelling techniques to generate the estimates based on other available variables or data from countries with a similar health profile in the neighboring region for countries that have insufficient data. In this study, we used data on the numbers of mortality, crude death rate, and DALY rate. Moreover, the incidence of cervical cancer was not examined.

Cervical cancer is becoming a major problem in the EMR, and its burden might increase due to the population growth. There is a need for effective interventions to reduce the burden of cervical cancer. This includes prevention measures such as HPV vaccination, early detection of cervical cancer, and reducing the risk factors associated with cervical cancer.