Disease burden and mortality estimates
According to the GBD Study 2019, DALYs due to PLCs deteriorated from 5.91 to 8.83 million between 1990 and 2019, especially for other pharynx cancer, which doubled in the same period (Supporting Table 1). The number of deaths caused by PLCs was 309.16 thousand in 2019 and 192.38 thousand in 1990. Thus, during the past 30 years, death and DALYs for PLCs increased by 60.7% and 49.41%, respectively. Specifically, the age-standardized mortality rate declined in larynx cancer and nasopharynx cancer but increased in other pharynx cancer. At the same time point, the gap was wider among men than among women (Supporting Table 1). Estimates of mortality rates by country are presented in Supporting Table 2. The mortality rate of PLCs in various countries around the world demonstrated a very large gap, even up to dozens of times, which will be discussed in detail later in this article.
Other Pharynx Cancer
In 2019, 114.2 (95% CI: 103.2 to 126.0) thousand deaths were attributed to other pharynx cancer. The age-standardized mortality rate of other pharynx cancer among countries is shown in Fig. 1. The highest rate was in India (4.89, 95% UI: 4.05 to 5.84) per 100,000 people and was much higher than that in Palestine, wherein the lowest rate was 0.19 (95% UI: 0.16 to 0.22) per 100,000 people. Countries or regions with age-standardized mortality rates above 2.0 per 100,000 people were Europe (Ukraine, Lithuania, Slovenia, Republic of Moldova, Romania, Hungary, and Slovakia), Oceania (American Samoa), Asia (Brunei Darussalam, Viet Nam, Bangladesh, Nepal, Pakistan, Bhutan, and India), North America (Greenland and Dominica), and Africa (Seychelles). Globally, the age-standardized mortality rate increased from 1.25 (95% UI: 1.17 to 1.37) per 100,000 people to 1.37 (95% UI: 1.24 to 1.51) per 100,000 people for 30 years. The average increase in the age-standardized mortality rate was 0.25% annually, with a 95% CI of 0.21–0.29%. The country with the most intense decrease in EAPC from 1990 to 2019 was Puerto Rico, with a 3.33% (95% CI: 3.98–3.68%) reduction annually. Romania occupied the other extreme, with the largest annual increase of 3.23% (95% CI: 2.97–3.49%) annually (Fig. 1).
Larynx Cancer
Approximately 123.3 (95% uncertainty interval: 114.9 to 132.8) thousand people died from larynx cancer in 2019, while the number was nearly 87.46 (95% UI: 83.18 to 91.55) thousand in 1990 (Supplemental Table 1). The number of deaths from larynx cancer has risen by one-third in 30 years. A global view of a wide range of age-standardized mortality rates attributable to larynx cancer in 2019 is provided in Fig. 1. The age-standardized mortality rates exceeded 5 per 100,000 people in Pakistan (5.75, 95% UI: 4.47 to 7.44), Seychelles (5.12, 95%UI: 4.34 to 6.06), and Cuba (5.03, 95% UI: 4.08 to 6.15). Mortality rates below 0.5 per 100,000 people were seen only in developed countries in Asia (Japan and Singapore), Europe (Sweden, Finland, Norway, and Iceland), and Oceania (New Zealand and Guam). From 1990 to 2019, the global age-standardized mortality rate of larynx cancer dropped by an average of 1.50% (95% CI: 1.42–1.57%) annually. Figure 1 shows that the country with the fastest decline in mortality rate was the Republic of Korea, with a reduction of 6.51% (95% CI: 5.90–7.11%). Nevertheless, the mortality rates in 35 countries increased, and the fastest increase was noted in Guinea (1.73%, 95% CI: 1.53–1.93%).
Nasopharynx Cancer
Figure 1 shows the global age-standardized mortality rates of nasopharynx cancer with a great difference in the regional distribution in 2019. Malaysia has a maximum age-standardized mortality rate of 4.76 (95% UI: 3.65 to 6.08) per 100,000 people in 2019. Finland had the lowest mortality rate (0.10, 95% UI: 0.09, 0.11). The mortality rate of nasopharynx cancer is generally low worldwide[12]. Other countries or territories with mortality rates of nasopharynx cancer above 2.0 were Africa (Uganda and Libya), Oceania (Solomon Islands), Asia (Taiwan [Province of China], Guam, Northern Mariana Islands, Viet Nam, and Brunei Darussalam), and North America (Greenland). The mortality rate of nasopharynx cancer showed a significant regional distribution, and the countries and regions with the highest rates were mainly concentrated in Asia. The average decrease in the global age-standardized mortality rate associated with nasopharynx cancer from 1990 to 2019 was 1.48% (95% CI: 1.39–1.57%) annually. The largest decrease in mortality rate was found in Singapore (4.30%, 95% CI: 4.00–4.60%). The mortality rate with the most obvious annual increase occurred in Romania (3.02%, 95% CI: 2.23–3.83%).
Sex And Age Differences In Mortality And Dalys
From 1990 to 2019, the trend of the age-standardized DALY rates and age-standardized mortality rates declined for larynx cancer and nasopharynx cancer, except for other pharynx cancer, which showed a slight upward trend (Fig. 2). Both the mortality rate and the DALYs were significantly higher in men than in women. For larynx cancer, the mortality rate and DALYs among women changed in a limited manner during this period, while those of men dropped dramatically.
Deaths attributed globally to larynx cancer, other pharynx cancer, and nasopharynx cancer in 1990 and 2019 by age and sex are shown in Fig. 3. Deaths caused by PLCs mostly occurred among people between the ages of 50 and 70 years, and significantly affected more males.
Correlation Between The Sdi And Estimates Of Mortality And Dalys
Associations between the SDI and age-standardized mortality rates due to larynx cancer, other pharynx cancer, and nasopharynx cancer are shown in Fig. 4. From 1990 to 2019, the mortality rates of larynx cancer and nasopharynx cancer declined in all five sociodemographic regions. The mortality rate of other pharynx cancer exhibited significant differences across SDI countries; low and low-middle SDI regions showed an upward trend and a mortality rate that was much higher than that of the other three regions. The correlations between the SDI and age-standardized mortality rates of countries and territories in 2019 were explored (Supporting Fig. 1). Negative correlations were found between the mortality rates and SDI for larynx cancer (R = -0.1511, P = 0.031) and nasopharynx cancer (R = -0.268, P = 0.0001), while a positive correlation was identified for other pharynx cancer (R = 0.2638, P = 0.0001). Not surprisingly, the relationship between annual trends and age-standardized DALY rates of countries and territories between SDI was close to the result of mortality rates (Supporting Fig. 2 and Supporting Fig. 3, respectively). The change in the SDI from 1990 to 2019 globally showed no significant correlation with EAPC in the age-standardized mortality rates of nasopharynx cancer and other pharynx cancer, except for larynx cancer (R = 0. 2171, P = 0.0019) (Supporting Fig. 4).
Risk Factors
Figure 5 shows all the critical risk factors attributed to the mortality rate of PLCs in every SDI region in 2019. In all SDI quintiles, smoking and alcohol use were the two most important risk factors for death from PLCs. While smoking was primarily responsible for deaths from larynx cancer and other pharynx cancer, alcohol use was the predominant risk factor for deaths from nasopharynx cancer. In regions with low and low-middle SDI, smoking was the most common cause of death from other pharynx cancer. From 1990 to 2019, smoking and alcohol use were the two most important risk factors for mortality rates and DALYs attributable to PLCs and presented a significant downward trend except for other pharynx cancer attributed to alcohol use (Supporting Figs. 5 and 6). In 2019, approximately 2.40 million (95% UI: 2.09 to 2.73) and 1.01 million (95% UI: 0.68 to 1.27) DALYs attributable to larynx cancer were caused by smoking and alcohol use, respectively (Supporting Fig. 6). The same dominant risk factors were also observed in other pharynx cancer (1.49 million, 95% UI: 1.19 to 1.77 million), while alcohol use replaced smoking as the primary leading cause (0.96 million, 95% UI: 0.75 to 1.18) for nasopharynx cancer (Supporting Fig. 6). The effects of smoking and alcohol use on DALYs and mortality rates were further explored in terms of sex. Not surprisingly, both risk factors affected men far more than women (Supporting Fig. 7). For larynx cancer, DALYs attributable to occupational exposure to sulfuric acid and asbestos were relatively small (0.148 million and 0.086 million, respectively) in 2019. The effect of occupational factors on nasopharynx cancer is also shown in Supporting Fig. 6; formaldehyde contributed much less to DALYs than did alcohol use and smoking.
Deaths caused by all critical risk factors in the different SDI regions were analyzed. In 2019, the correlations between SDI and age-standardized mortality rate of larynx cancer attributable to alcohol use (R = 0.2549, P = 0.0002), smoking (R = 0.1547, P = 0.0272), and occupational asbestos exposure (R = 0.4633, P < 0.0001) were significantly positive, while the correlation for occupational exposure to sulfuric acid was negative (R = -0.2322, P = 0.0008) (Supporting Fig. 8). Supporting Fig. 9 shows the positive correlation between SDI and age-standardized mortality rate of other pharynx cancer caused by alcohol use and smoking (R = 0.462, P < 0.0001 and R = 0.4111, P < 0.0001, respectively). Death due to nasopharynx cancer attributable to smoking (P = 0.6414) and alcohol use (P = 0.995) showed no significant relationship with SDI, while occupational exposure to formaldehyde showed a significantly negative correlation (R = -0.4934, P < 0.0001) (Supporting Fig. 10).