Favorable cervical cancer mortality-to-incidence ratios of countries with good human development index rankings and high health expenditures

Cervical cancer is a common cancer worldwide, especially in developing countries, which constitutes a significant health threat and economic burden on healthcare systems [2]. Previous systematic reviews, meta-analyses, and observational studies have consistently showed that screening program can decrease the incidence of cervical cancer [13]. One study from the Setif Cancer Registry, Algeria (1986–2010), documented decreased cervical cancer incidence rates in the period 1986–2010 (annual percentage change: -4.2%), which was attributed to opportunistic cytology screening [14]. In a randomized trial of over 130,000 patients in rural India, a single lifetime screen with HPV testing reduced cervical cancer mortality by 50%, as compared with no screening (12.7 vs. 25.8 per 100,000 person-years, hazard ratio 0.52, 95% confidence interval 0.33–0.83) [15]. As cervical cancer is one of the most preventable and (if diagnosed early) treatable forms of cancer, it can be regarded as a global health problem.

To our knowledge, this is the first study to investigate the associations among the MIR for cervical cancer and the HDI, CHE. Our study indicated a significant correlation between the HDI and the MIR for cervical cancer in different countries. More support of healthcare expenditure, either through personal funding or country-based programs, led to lower MIRs for cervical cancer. This reflects the importance of the availability of early cancer screening, HPV vaccination programs, and advanced cancer treatments (e.g., surgery, concurrent chemoradiotherapy) in countries with better healthcare rankings.

Although Pap smear screening offers the opportunity for early diagnosis of cervical cancer, many women were diagnosed as invasive cervical cancer cases. Most of them had never been screened or participated in routine screening, even in countries with well-organized screening programs based on cytology and good coverage [16]. In Asian countries (e.g., Taiwan), culture-specific barriers to Pap testing led to a significantly lower coverage among elderly women. Chou et al. explained the reasons for Pap smears avoidance among Taiwanese women, which included fear of discomfort or pain, shyness, lack of medical knowledge, lack of a sense of urgency, busyness, loss of confidence in Pap smear screening, the feeling that it is not possible to get cervical cancer, and not being able to face bad news [17]. In our study, Japan had the higher incidence and mortality of ASR and Asia countries had higher MIR, as compared to Western countries with similar economies (Table 1, 2). One option to solve the problem of low Pap screening percentage is HPV-based screening, which allows for high sensitivity rates over cytology. For Pap smear under-users, HPV-based screening offers the possibility of self-sampling and makes possible longer screening intervals in women with negative screening results. It is a way to improve under-screening by self-sampling with sample kits offered in communities or mailed directly to homes. Based on an updated meta-analysis by Maver et al., the diagnostic accuracy of PCR-based high-risk HPV assays were equally sensitive for underlying CIN2 + or CIN3 + on self-samples versus clinician-collected samples. Some European countries have implemented HPV-based screening since July 2019 [18]. Countries with low Pap smear screening rates may consider the transition to HPV-based cervical cancer screening in the future to improve their MIR.

Different cancer types have different MIR patterns among countries with “different civilization”. We compared cervical cancer to other cancers, for example, lung cancer, colorectal cancer, prostate cancer, liver cancer, gastric cancer, and pancreas cancer. Cervical cancer, as well as colorectal cancer, showed lower incidence and mortality rates and lower MIRs in high-income countries [12]. Well screening guidelines may explain the lower MIRs.

On the contrary, gastric cancer, lung cancer, and prostate cancer had higher incidence and mortality rates but lower MIR values in high-income countries compared to low-income countries. These cancers can be divided into “diseases of civilization” [19]. The high incidence and mortality rates might be associated with the Western diet and more sedentary lifestyle, while early detection methods and early-stage cancer with immediate treatment resulted in low MIRs in higher developed countries [11, 12, 20‐23].

Another pattern of association occurred in pancreatic cancer, which had high incidence and mortality rates in developed countries. Meanwhile, its MIR did not correlate with healthcare disparities among countries [22]. This could be because pancreatic cancer is a highly lethal disease and most cases are usually detected in the advanced stages because of no efficient screening methods [1]. Therefore, more healthcare expenditure, either through personal funding or country-based programs, cannot improve disease outcome in this disease pattern.

To our knowledge, this is the first study to address the association among the MIRs for cervical cancer and the HDI, CHE. This can potentially guide government to manage health expenditure among their healthcare systems. Our study showed lower incidence and mortality rates for cervical cancer in countries characterized by a better HDI. The MIRs of different countries were also negatively correlated with the HDIs. The MIR is therefore a potentially useful parameter for monitoring the screening and healthcare treatment status of cervical cancer. Therefore, we need to integrate current interventions into existing health plans to reduce the future burden from cancer.

There were some limitations of our study which need to be taken into account. First, no detail clinical information was analyzed, e.g. cervical cancer stage and screening program. Second, many countries were excluded due to low data availability, with only 61 countries recruited for the final analyses.

In this study, we demonstrated that the MIR for cervical cancer is associated with healthcare disparities. As observed better outcome after the implementation of Pap smear screening tests, we are expecting to see further and better results for HPV vaccination and HPV-based cervical cancer screening. The promotion of highly effective cancer screening programs is a feasible option in Taiwan and other countries. It can improve under-screening problem and reduce the global incidence and mortality rates as well as the MIRs for cervical cancer.