Mortality due to oral and oropharyngeal cancer in Uruguay from 1997 to 2014

Abstract Oral and oropharyngeal cancer is considered a public health problem in several countries due to its high incidence and mortality rate. Objective: This study aimed to analyze oral and oropharyngeal cancer mortality in Uruguay from 1997 to 2014 by age, sex and country region. Methodology: A time series ecological study using secondary data was performed. Data on mortality due to oral and oropharyngeal cancers were obtained from the Vital Statistics Department of Uruguay's Ministry of Public Health. Results: The cumulative mortality rate due to oral and oropharyngeal cancer over the study period was of 19.26/100,000 persons in women and 83.61/100.000 in men, with a mean annual rate of 1.75/100,000 in women and 7.60/100,000 in men. Mortality rate from both sites during the study period was 4.34 times higher in men than in women. Malignant neoplasms of other parts of the tongue and base of tongue showed the highest mortality rate. The means of the annual coefficients of deaths were higher for the age groups between 50 and 69 years. Higher mortality rates of oral and oropharyngeal cancer were observed in Artigas (4.63) and Cerro Largo (3.75). Conclusions: Our study described a high mortality rate for oral and oropharyngeal cancer in Uruguay from 1997 to 2014. According to the country's health department, men, tongue cancer, and oral cavity had higher mortality rates, with some variation. Prevention strategies with control of risk factors and early diagnosis are necessary to improve survival in the Uruguayan population.


Introduction
Head and neck squamous cell carcinoma (HNSCC) is in the group of malignant tumors originated in the oral cavity, oropharynx, hypopharynx, and larynx. 1 According to the International Agency for Research on Cancer (IARC), HNSCC affected more than half a million people in 2012, and, of these, 300,373 cases were oral squamous cell carcinoma (OSCC). 2 An estimate of 325,000 deaths have been annually attributed to HNSCC around the world. 3 OSCC is considered a serious public health problem in several countries due to its high incidence and mortality rate. 1,4 Several factors increase the OSCC development risk and seem to act by increasing the rates of cellular mutation. Exogenous factors related to lifestyle, especially tobacco and alcohol consumption, seem to be particularly important. HPV infection is usually associated with oropharyngeal cancer as well. 5 Uruguay is a South American country, which is home to 3,286,314 million people and 43% of the population live in the capital, Montevideo. 6 The National Cancer Program of Uruguay published their survey of cancer (2007 to 2011) and showed that oropharyngeal cancer is the seventh most common cancer in the country. It showed a higher incidence in men (n=1,079 cases) and a rate of 10.33 cases per 100,000 men and 2.76 cases per 100,000 women. In the capital, 468 cases occurred in men, equivalent to 11.37 per 100,000 men, and 201 cases in women, accounting for 2.99 cases per 100,000 women. 7 A study performed by Oliveira, et al. 8 (2015) analyzing the profile of the primary oral squamous cell carcinoma (OSCC) in Uruguay found that the male:female ratio was 3.8:1, the average age was 60.75 years (±11. 26) for the population studied, and 42.5% of the cases occurred on the tongue. The study concluded that OCCS diagnosis in Uruguay is at late stages, with a poor prognosis and low survival rate.
In Uruguay between 2004-2008, the mortality rate for oral and pharynx cancer was 6.46/100,000 in men and 1.16/100,000 in women. 9 Until now, no study has been completed in Uruguay analyzing both sites for a long period of time. Also, understanding the behavior of the disease over time is important to guide public health policies directed towards screening, to monitor the results of therapies used and establish epidemiological surveillance and control of oral and oropharyngeal cancer. Studies that specifically analyze these regions are non-existent in Uruguay.
Thus, this study aimed to assess the rate of oral and oropharyngeal cancer mortality in Uruguay and its rates by age, sex, and regions of the country.

Methodology
This is a descriptive ecological study using secondary data. Data on mortality due to oral and oropharyngeal cancer between 1997 and 2014 were  Table 1 shows the distribution of the deaths from 1997 to 2014, considering these five categories, and the ratio between the male and female crude mortality rates, for each category and total. The ratio between male and female rates was 3.23:1, the lowest ratio was for salivary gland cancer (1.83:1) and the highest ratio was for oropharyngeal cancer (6.40:1). Oropharyngeal cancer included the sub-sites, as described by WHO, such as the base of the tongue, tonsils and oropharynx and was responsible for 616 (36.30%) deaths (Table 2). Table 3 shows that the mean of the annual coefficients and the (cumulative) coefficients for the whole period, adjusted for sex and age group (per 100,000 inhabitants), for females and males and For the 20-29 age group, it was observed that no cases were reported before 2004. not available due to a failure in the database) for each age group and the average of the annual coefficients adjusted by sex and age group (per 100,000 inhabitants). The means of the annual coefficients were higher for the age groups between 50 and 79 years. The mean of the annual coefficients and the (cumulative) coefficients for the whole period, adjusted for sex and age group (per 100,000 inhabitants) was 2.74 in women and 11.94 in men for each age group and the proportion between these (M/F) coefficients for the period was 4.84. (Table 4). The mortality rates by oral and oropharyngeal cancers during the study period was 4.34 times higher in men than in women and the age group between 40-49 years had the highest M/F coefficient (10.88), followed by the

Discussion
To understand the mortality rate due to oral and oropharyngeal cancers for a population may influence new strategies to improve prevention and promote early diagnosis policies for these diseases. This study is the first one that assess, over a long period of time, the mortality rate by oral and oropharyngeal cancer in Uruguay according to sex, age, anatomic site, and geographical distribution. In general, our main findings reveal higher mortality rates in cases of oral cavity cancer compared to oropharyngeal cancer.
Tongue cancer affecting men who live in the capital of the country showed the highest rates of mortality   Our results found that of 1.696 deaths registered in the study period, the oral cavity (63.70%) was more affected than the oropharynx (36.30%). This differs from the study published by Perea, et al. 10 (2018), which revealed more deaths due to pharyngeal cancer than oral cavity cancer in Brazil, but when tonsils and oropharyngeal (except for the base of the tongue) cancers were considered, the average was similar in both regions. In Germany, Hertrampf, et al. 11 (2015) reported that 54% of deaths were related to pharyngeal cancer, 40% to oral cavity cancer and 6% due to salivary gland cancer. Explaining the differences among our results and other studies is difficult, but one possible hypothesis is that Brazil and Germany have more effective strategies for oral cancer prevention or early diagnosis that impact the mortality rates for pharyngeal cancer.
We observed that tongue cancer was related to higher rates of mortality, since 440 cases of cancer were reported in the oral cavity and 224 cases in the oropharynx. These results agree with the data described by Oliveira, et al. 8 (2015), which found that, in Uruguay, oral cancer is more prevalent on the tongue and its diagnosis tend to be at a later stage. Other studies also showed a higher mortality for tongue cancer, varying between 20% to 50% of cases. 12,13 Several studies suggested that lack of oral examinations, late diagnosis and advanced stage of the diseases were the main causes of higher mortality rates associated with tongue tumors. 14-15 Moreover, tongue tumors usually cause early metastases in the lymph nodes, promoting an increase in the mortality rate. 16 The death rates between men and women have been studied extensively. 17-20 Most countries estimate oral and oropharyngeal cancer mortality to be 3-4 per 100,000 men and 1.5-2 per 100,000 women at ageadjusted rates, and studies often indicate that women have a higher survival rate than men. 1,21 Our results showed that deaths from oral and oropharyngeal cancers in Uruguay during 1997-2014 were 4.34 times greater in males than in females. These findings confirm previous studies worldwide. 1,17,19,22 However,  This study is based on secondary information data registered with the National Statistics Institute of Uruguay. This type of study design has limitations because it is dependent on the accuracy and completeness of available information systems.
Another limitation is related to the study design.
Ecological studies are useful for raising hypotheses; however, they are not able to provide information about causality. According to IARC-WHO evaluation of registry data worldwide, the registry tracking the incidence of cancer in Uruguay is a high quality instrument, while mortality information is classified as medium quality registration data.

Conclusions
Our results found that mortality due to oral cancer is higher than oropharyngeal cancer. In both sites, tongue cancer, men, and adults between 50 and 69 years old showed higher mortality rates. Improving the control of risk factors, mainly tobacco and alcohol, investigating HPV-status and implementing strategies for prevention and early diagnosis of these lesions is important.