The unacceptable case fatality risk observed worldwide
James Fleck, MD, PhD: Anticancerweb 31 (03), 2021
Cervical cancer is a malignant tumor that appears in the epithelial cells of the lower segment of the uterus (cervix) and is associated with the human papilloma virus (HPV). Worldwide, more than 600,000 cases are diagnosed annually. It is the fourth malignant tumor in incidence (ASR = 13.7) and mortality (ASR = 7.3). In Africa, cervical cancer reaches the second position in the ranking of malignant diseases, assuming an even higher incidence (ASR = 25.6) and mortality rate (ASR=17.7). Data published by the International Agency for Research on Cancer (IARC), a Division of World Health Organization (WHO) gives us a comprehensive idea of the magnitude of the problem. Table 1 shows the most important cervical cancer epidemiological data in five continents.
Table 1: Female cancer epidemiological data
A preliminary analysis of Table 1 gives us the impression that cervical cancer is a major health problem only in Africa, Asia and Latin America, as its incidence and mortality rates barely reach the tenth position in Europe and Northern America. However, it is necessary to look beyond these numbers to really understand the global magnitude of the problem. Both incidence and mortality rates indicate the number of cases per 100,000 inhabitants. Table 2 describes the incidence and mortality rates of cervical cancer in five continents. Data are expressed in Age-Standardized Rate (ASR), allowing populations to be compared, since age distribution is quite different in the five continents, which definitively influences the crude incidence and mortality rates. Both are very important epidemiological parameters, but insufficient to clearly express the impact of medical interventions that favor early diagnosis, as well as advances in adjuvant treatment.
Table 2: Incidence and mortality of cervical cancer expressed in ASR in five continents
Let's look at the case fatality risk (CFR), which means the proportion (%) of women who die from cervical cancer among the total number of women diagnosed with the disease in one year. Table 3 shows the CFR for all cancer, female cancer and cervical cancer in five continents. The magnitude of differences can be seen in figure 1. The figure shows that the magnitude of the differences in CFRs are smaller in cervical cancer than those observed for all types of cancer or for female cancer across the five continents.
Table 3: CFR for all cancer, female cancer and cervical cancer in five continents
Figure 1: Magnitude of the CFR in five continents
The high CFR for cervical cancer observed in both Europe (CFR = 44.68) and Northern America (CFR = 42.37) indicates cervical cancer diagnosed in more advanced stages and/or not subjected to the best curative approach. In fact, the USA cancer statistics published by the American Cancer Society in 2019 showed that 51% of women were diagnosed with advanced or metastatic cervical cancer. Figure 2 illustrates the comparison between the three epidemiologic parameters in the five continents. Lower cervical cancer incidence and mortality rates in Europe and North America are not accompanied by an expected lower CFR.
Figure 2: Cervical cancer incidence, mortality and case fatality rate (CFR) in five continents
Cervical cancer is a malignant disease that should have been overcome in the world. The Pap smears or Pap test was introduced in the book Diagnosis of Uterine Cancer by the Vaginal Smear published in 1943, authored by Georgios Nikolaou Papanikolaou and Herbert Frederick Traut, describing a simple and reproducible technique that allowed the early diagnosis of cervical cancer. Since 1950, all American cancer societies joined efforts in the strong recommendation of exfoliative cytology (Pap test) all over the world. Later on, by the turn of XXI century, HPV next-generation hybridization has been used in the histologic diagnosis of cervical intraepithelial neoplasia grade 2+ (CIN2+) providing an even earlier diagnosis. The sensitivity of Pap smears and HPV test are 55.4% and 94.6%, respectively. Conversely, Pap smears has a specificity of 96.8% compared to 94.1% for the HPV test. The negative predictive value of both tests is 99%, which leads to a very precise and very early diagnosis. Recently, researchers from the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA identified artificial intelligence as a simple, universal and reliable ally for an accurate cervical cancer screening. Published in January 2019 in the Journal of National Cancer Institute, a population-based longitudinal study validated the use of digitalized uterine cervix images in the identification of premalignant lesions (CIN2 and CIN3) as well as carcinoma in situ (CIS). Tested in Costa Rica high risk women population, the new method revealed a higher accuracy (AUC = 0.91) when compared to conventional cytology of the uterine cervix (AUC = 0.71). All of these screening methods are now available, allowing early diagnosis of cervical cancer and subsequent appropriate interventions, leading to a cure rate that is close to 100%. A globally observed CFR of more than 40% is unacceptable. Failure to provide effective educational programs and social inequality are the main causes for this universal health disaster.
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6. Photo by Jonathan Ford on Unsplash