The incidence and mortality of lip and oral cavity cancer and its relationship to the 2012 Human Development Index of Asia

Introduction : Lip and oral cavity cancer is one of the most prevalent cancers in Asia and considered to be a major public health problem due to the low survival rate. Because of the importance of access to information about this cancer (including incidence, mortality rate and relation to socioeconomic indicators), this study aims at investigating the incidence and mortality of lip and oral cavity cancer and its relationship with the Human Development Index (HDI) of Asia (from 2012). Method: This study was an ecological study in Asia for assessment of the correlation between age-specific incidence rate (ASIR) and mortality (ASMR) HDI Data on (SIR) (SMR) We used a bivariate method for assessment of the correlation between the SIR and SMR with the HDI and its individual components. Statistical significance was assumed if P<0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.). Results: A total incidence of 162,506 cases and 95,005 deaths were recorded in Asian countries in 2012. Countries with the highest SIR (per 100,000) were the following: Maldives (11), Sri Lanka (10.3), Pakistan (9.8), Bangladesh (9.4), and India (7.2). The highest SMR was observed in the following countries: Pakistan (5.9), Bangladesh (5.6), Afghanistan (5.1), India (4.9), and Maldives (4.1). The correlation between SIR of lip and oral cavity cancer and HDI was -0.378 (p=0.010), with life expectancy at birth at -0.324 (p=0.028), mean years of schooling at -0.283 (p=0.057), and level of income per each person of the population at -0.279 (p=0.060). Moreover, the correlation was -0.664 (p ≤ 0.001 ) between SMR and HDI. Conclusion: A significant reverse correlation was seen between the incidence and mortality rate of lip and oral cavity cancer and the HDI in Asia. The incidence and mortality of this type of cancer was high in developing or less developed countries.


Introduction
Cancers are among the leading causes of disease burden and mortality in the world and are regarded as a significant and growing public health problem around the world (Global Burden of Disease Cancer, 2015; Torre et al., 2015). Among cancers, lip and oral cavity cancer is the result of aggressive tumors originating from external lip and oral cavity and is the eighth most common cancer in men and the fourteenth most common cancer in women worldwide (de Camargo Cancela et al., 2010;Farah et al., 2014). In 2012, 14.1 million new cancer cases and 8.2 million cancer deaths occurred in the world; among them, 300,400 new cases and 145,400 deaths were due to lip and oral cavity cancer, accounting for more than 2% of new cases and 1.7% cases of death in the world, respectively (Torre et al., 2015). Most cancers of the lip and oral cavity have the same preventable risk factors (Warnakulasuriya, 2009). Smoking, alcohol, and chewing tobacco and betel quid (synergistic relationship) are the main risk factors for this type of cancer (Lin et al., 2005;Monteiro et al., 2013;Neville and Day, 2002;Warnakulasuriya, 2009). Poor eating habits, sun overexpsoure, viral infections (particularly human papillomavirus (HPV)), poor oral hygiene, and ISSN: 2198-4093 www.bmrat.org socio-economic factors are also important risk factors for lip and oral cavity cancers ( de Camargo Cancela et al., 2010;Farah et al., 2014;Funk et al., 2002;Ribeiro et al., 2015;Warnakulasuriya, 2009).
There is a large geographic variation in the incidence of lip and oral cavity cancer. The highest incidence rates have been reported from Malaysia, South Central Asia, and East and Central Europe, while the lowest rates have been reported from West Africa and East Asia. In recent decades, the incidence rate of lip and oral cavity cancers have decreased in men and women from Asia, North America and Australia, and in men from South and West Europe. However, the rates have increased in men and women from East and North Europe and in women from South and West Europe. The main reasons for this are the rising tobacco epidemic trend as well as the increased prevalence of HPV infection in some countries (Torre et al., 2015;Yako-Suketomo and Matsuda, 2010). Lip and oral cavity cancer is 90% squamous cell carcinoma and is often seen in middle-aged and older people. Its mortality is higher in men and black people, but lower in women (due to less exposure to risk factors such as smoking and alcohol) (de Camargo Cancela et al., 2010;Funk et al., 2002;Neville and Day, 2002;Yako-Suketomo and Matsuda, 2010).
Studies have shown that socioeconomic inequalities which affect behavior and lifestyle have a relation to the incidence and mortality rates of oral cavity cancer. However, some studies have shown conflicting results (Chen et al., 2009;de Camargo Cancela et al., 2010;Patel et al., 2012;Warnakulasuriya, 2009). To review countries' economic and social conditions, various indicators have been defined. One of the most important of the indicators is the Human Development Index (HDI) (Giebel et al., 2010;Hu et al., 2013). This index was first used by the United Nations Development Program and is a combination of three major factors-longevity, knowledge, and standard of living. The HDI is represented as a number between zero and one. Longevity is measured by life expectancy at birth and expressed as Life Expectancy Index. Knowledge is evaluated by a combination of adult literacy rate and the rate of enrollment at primary, secondary and tertiary schools (Education Index). The standard of living is measured by the Gross Domestic Product per capita, with purchasing power parity in US dollars (Gross Domestic Product Index) (Giebel et al., 2010;Hou et al., 2015;Rahi, 2011).
Some studies have shown the relationship between HDI and cancer incidence and mortality (Fidler et al., 2016;Pakzad et al., 2016;Rafiemanesh et al., 2016;Razi et al., 2016). However, to date, no study has been conducted to investigate the relationship between the HDI and the incidence and mortality of lip and oral cavity cancer in Asia. Knowledge of information about the incidence and mortality of lip and oral cavity cancer and its related factors can be useful for planning and developing policies related to health care. This study was aimed to determine the standardized incidence ratio (ASIR) and the standardized mortality ratio (SMR) of lip and oral cavity cancers, and the relationship of ASIR and ASMR with the 2012 HDI of Asian countries.

Methods
This study was an ecological study in Asia with the goal of assessing the correlation between age-specific incidence and mortality rates of lip and oral cavity cancer with the Human Development Index (HDI) and its components (life expectancy at birth, mean years of schooling, and gross national income per capita. Data about the age-specific incidence and mortality rates for every Asian country for the year 2012 were obtained from the global cancer project available online (http://globocan.iarc.fr/Default.aspx) (Ferlay J S, 2012). The HDI from the Human Development Report of 2013 (Malik, 2013) included information about the HDI and its components for every country in 2012.
A method of age-specific incidence and mortality rates from the global cancer project of the International Agency for Research on Cancer (France) was previously reported (Ferlay et al., 2014;Jemal et al., 2011;Torre et al., 2015).

Human Development Index (HDI)
The Human Development Index (HDI) is derived from a composite measure of indicators along three dimensions: life expectancy at birth, mean years of schooling and level of income per each person of the population (i.e. gross national income per capita) (Malik, 2013).

Statistical analysis
In this study, we used the correlation bivariate method for assessment of correlation between age-specific incidence and mortality rates with HDI and its components (including life expectancy at birth, mean years of schooling and gross national income per capita. Statistical significance was assumed if P< 0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS software (Version 15.0, SPSS Inc.).
Of the Asian countries, the 5 countries with the highest standardized incidence rates of lip and oral cavity cancer were: 1) Maldives (standardized rate of 11 per 100,000 people), The number as well as crude and standardized incidence rates of the cancer, according to sex, of the Asian countries are presented in Table 1. The countries are classified from highest to lowest, based on standardized incidence rates. The highest and lowest standardized incidence rates are indicated for both sexes ( These five countries, collectively, had a sum of 80,731 cases (84.97%) of deaths.
Conversely, the 5 countries with the lowest standardized mortality rates of lip and oral cavity cancer were: The number as well as crude and standardized mortality rates of the cancer, according to sex, of the Asian countries are presented in Table 2. The countries are classified from highest to lowest, based on standardized mortality rates. The highest and lowest standardized mortality rates are indicated for both sexes ( Table 2, Fig. 1).

Assessing the relationship between standardized incidence rate and the Human Development Index
Overall, a negative correlation of 0.378 was seen between the standardized incidence rate of lip and oral cavity cancer and the HDI; the correlation was statistically significant (P=0.010). A negative correlation was also seen between components of the HDI and the standardized incidence rate. Moreover, a negative correlation was seen when assessing the relationship of the standardized incidence rate to life expectancy at birth ( In men, a negative correlation of 0.323 was seen between the standardized incidence rate of lip and oral cavity cancer and the HDI; the correlation was statistically significant (P=0.029). A negative correlation was also seen between components of the HDI and the standardized rate. Moreover, a negative correlation was seen when assessing the relationship of the standardized incidence rate to life expectancy at birth (0.279; P=0.061), to mean age of education (0.167; P=0.267), and to level of income per person of the population (0.323; P=0.029). In women, a negative correlation of 0.337 was seen between the standardized incidence rate of lip and oral cavity cancer and the HDI; the correlation was statistically significant (P=0.022). A negative correlation was also seen between components of the HDI and the standardized rate. Moreover, a negative correlation was seen when assessing the relationship of the standardized incidence rate to life expectancy at birth (0.310; P=0.036), to mean age of education (0.348, P=0.018), and to level of income per person of the population (0.132; P=0.382).

Assessing the relationship between standardized mortality rate and the Human Development Index
Overall, a negative correlation of 0.664 was seen between the standardized mortality rate of lip and oral cavity cancer and the HDI; the correlation was statistically significant (P≤0.001). Also, a significant negative correlation was seen between components of the HDI and the standardized rate. In fact, a negative correlation was seen when assessing the relationship of the standardized mortality rate to life expectancy at birth (0.592; P≤0.001), to mean age of education (0.528; P≤0.001), and to level of income per person of the population (0.421; P=0.004).
In men, a negative correlation of 0.603 was seen between the standardized mortality rate of lip and oral cavity cancer and the HDI; the correlation was statistically significant (P≤0.001). Also, a significant negative correlation was seen between components of the HDI and the standardized rate. In fact, a negative correlation was seen when assessing the relationship of the standardized mortality rate to life expectancy at birth (0.518; P≤0.001), to mean age of education (0.448; P=0.002), and to level of income per person of the population (0.429; P=0.003).
In women, a negative correlation of 0.666 was seen between the standardized mortality rate of lip and oral cavity cancer and the HDI; the correlation was also statistically significant (P≤0.001). Moreover, a significant negative correlation was seen between components of the HDI and the standardized rate. In fact, a negative correlation was seen when assessing the relationship of the standardized mortality rate to life expectancy at birth (

Discussion
Although lip and oral cavity cancer accounts for less than 3% of all cancer cases worldwide, its low survival rate and adverse consequences on quality of life have garnered it to be considered as a significant public health problem; in fact, two thirds of its burden occurs in developing countries (Costa et al., 2016;Farah et al., 2014;Global Burden of Disease Cancer, 2015;Ribeiro et al., 2015;Torre et al., 2015;Warnakulasuriya, 2009). Studies show that 162,506 new cases of lip and oral cavity cancer have been recorded in Asia in 2012, accounting for 56.1% of all new cancer cases worldwide in 2012. There was a significant inverse relationship between the lip and oral cavity cancer and the HDI in Asia. The highest standardized incidence rates for this type of cancer, among the Asian countries, were seen in Maldives, Sri Lanka, Pakistan, Bangladesh and India, respectively. These countries were among the countries with medium HDI.
Since people who live in developing countries are exposed to a wider range of risk factors for cancer of the lip and oral cavity, the highest incidence rates are reported from these countries (Byakodi et al., 2012;de Camargo Cancela et al., 2010;Gupta et al., 2016;Rastogi et al., 2004). The most important risk factors of this cancer are tobacco use, alcohol, chewing tobacco, betel quid, poor eating habits, sun exposure, viral infections (especially HPV), and poor oral hygiene (de Camargo Cancela et al., 2010;Farah et al., 2014;Funk et al., 2002;Ribeiro et al., 2015;Warnakulasuriya, 2009). In India and Pakistan, about 100 million people use various types of smokeless tobacco and betel-quid chewing (Jayalekshmi et al., 2009). In addition to these countries, these tobacco and chewing habits are also common in Bangladesh, Afghanistan, Maldives, Sri Lanka and Nepal, which has led to an increased risk of lip and oral cavity cancers in these areas (Ariyawardana and Warnakulasuriya, 2011;Funk et al., 2002;Khan et al., 2016;Neville and Day, 2002;Sreeramareddy et al., 2014).
In the present study, an inverse relationship was seen between the incidence of lip and oral cavity cancer and the HDI components. The correlation was significant for life expectancy but insignificant for education and income. Studies have shown that the incidence of lip and oral cavity cancer is higher in people with lower education and income (de Camargo Cancela et al., 2010;Farah et al., 2014;Jayalekshmi et al., 2009;Johnson et al., 2010;Ribeiro et al., 2015;Swaminathan et al., 2009). People with less education are at greater risk of lip and oral cavity cancer due to less awareness of cancer risk factors, poor sanitary habits, greater consumption of alcohol and tobacco, and use of chewing tobacco (Gupta et al., 2016;Hashibe et al., 2003;Videnovic et al., 2016;Warnakulasuriya, 2009). Also, people with less income are more likely to have this type of cancer due to limited access to dental care, poor oral hygiene, consumption of fewer fruits and vegetables, greater HPV risk, and less protection against the sun (Arnold et al., 2016;Farah et al., 2014;Guha et al., 2007;Johnson et al., 2010;Monteiro et al., 2013;Morris et al., 2000;Pavia et al., 2006). Chen and colleagues also found an inverse relationship between income  (Conway et al., 2008).
Based on the data from Asia, 95,005 deaths occurred due to lip and oral cavity cancer in 2012, which was equivalent to 66.9% of all cancer deaths in the world that year. A significant inverse relation was seen between lip and oral cavity cancer mortality and the HDI. Asian countries with the highest standardized mortality rate from lip and oral cavity cancer were Pakistan, Bangladesh, Afghanistan, India and Maldives, respectively. Afghanistan had low HDI while the rest had medium HDI. The findings showed a significant inverse relation between mortality from lip and oral cavity cancer and the HDI components (including life expectancy, education and income). Studies have shown that less education, lack of awareness about the symptoms of lip and oral cavity cancer, and delayed diagnosis are all factor which contribute to higher mortality rates (Albano et al., 2007;Kilander et al., 2001;Warnakulasuriya, 2009).
Despite advances in medical sciences, over the past several decades the overall five-year survival rate for lip and oral cavity cancer has not improved significantly, remaining at about 50-55% (Neville and Day, 2002;Warnakulasuriya, 2009). In studies that were conducted in Asia, the overall five-year survival rate was 18% in Malaysia (Razak et al., 2010), 30.5 % in India (Yeole et al., 2003), 52.8% in Korea (Choi et al., 2014), and 61% in Taiwan (Liu et al., 2010). Due to limited access to diagnostic and treatment services in low-income communities and to the high cost of services, people present with advanced stage lip and oral cavity cancer at the time of diagnosis. All the aforementioned are among the important reasons for the low 5-year survival of patients as well as the higher mortality rates in developing countries (Funk et al., 2002;Global Burden of Disease Cancer, 2015;Patel et al., 2012;Sargeran et al., 2008). McDonald et al. reported in their study that there was lower survival of head and neck cancers, including oral cavity cancer, in people of low socioeconomic statuses (McDonald et al., 2014).
Mortality and high burden of lip and oral cavity cancer, particularly in developing countries, continues to warrant public education. Awareness about the risk factors and symptoms of lip and oral cavity cancer, screening of high-risk groups, and planning for preventative measures can help the population most at risk for this kind of cancer and will be essential for effective prevention (de Camargo Cancela et al., 2010;Warnakulasuriya, 2009

Conclusion
In general, a significant inverse correlation was observed between the incidence of lip and oral cavity cancer and the HDI in Asia. Moreover, the incidence of this cancer was higher in developing countries. This correlation was also observed between cancer incidence and the HDI components; it was significant for life expectancy but insignificant for education and income. A significant inverse correlation was observed between deaths from lip and oral cavity cancer and the HDI and its components, and the mortality rate from this cancer was higher in developing countries.

Abbreviations
HDI: Human Development Index: ASIR: Age-specific incidence rate ASMR: Age-specific mortality rate HPV: Human papillomavirus Acknowledgement Data on CANCER were obtained from the global cancer project and data on the HDI and its components were extracted from the World Bank site. Hereby we appreciate of the cooperation of all employees involved in data collection in the GLOBOCAN project and World Bank

Author contribution
All authors contributed to the design of the research. AMH, EI and HSG collected the data. AMH, EI and HS conducted analysis and interpretation of data. All authors drafted the first version. HS, AT and AMH edited the first draft. All authors reviewed and commented on final draft.