Lung cancer in central Tunisia: epidemiology and clinicopathological features.

Abstract

Lung cancer is the most common cancer worldwide but data from Tunisia are limited. The aim of this research was to describe the epidemiology, pathology and clinical features of lung cancer in Central Tunisia. All lung cancer cases diagnosed during a 15-year period were analyzed based on the data of the Cancer Registry of the Center of Tunisia. Five-year age-specific rates, world age-standardized rates (ASR), and annual percent change were calculated using annual data on population size and the estimated age structure. A total of 1,882 incident cases of lung cancer were registered (1,782 males, 100 females). The median age at diagnosis was 64 years for males and 61 years for females, with ASRs of 35.2 per 100,000 among males and 1.5 among females. Over time, there were significant decreasing trends by -6.5% (95% CI: -12.9%; -0.2%) for females and a stable incidence for males at an annual rate of +0.2% (95% CI: -1.6%; +1.8%). The predominant histological type was squamous cell carcinoma in males (36.9%) and adenocarcinoma in females (52%). During 2003-2007, adenocarcinoma became the most frequent (33.7%) followed by squamous cell carcinoma (30.3%) in males. The majority of tumor cases were diagnosed at advanced stages (79.9%). In conclusion, lung cancer has remained the most common cancer diagnosed at advanced stages among Tunisian men. Our findings justify the need to plan and develop effective programs aiming at the control and prevention of the spread of lung cancer in Tunisia.

Full text

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Asian Pacific Journal of Cancer Prevention, Vol 12, 2011
2305
Lung Cancer in Central Tunisia: Epidemiology and Clinicopathological Features
Asian Pacific J Cancer Prev, 12, 2305-2309
Introduction

the world for several decades, and by 2008, there were
an estimated 1.61 million new cases, representing 12.7%
of all new cancers (Ferlay et al., 2010). It was also the
most common cause of death from cancer, with 1.38
million deaths representing 18.2% of the total (Ferlay et
al., 2010). In males, lung cancer is still the most common
cancer worldwide with high rates in Central-Eastern and
Southern Europe, Northern America and Eastern Asia.
Very low rates are still estimated in Middle and Western
Africa. Incidence rates are generally lower in women, but,
worldwide, lung cancer is now the fourth most frequent
cancer of women with 516,000 cases and the second most
common cause of death from cancer with 427,000 deaths
(Ferlay et al., 2010).
Population-based studies describing the lung cancer
incidence were rarely reported from Tunisia (Missaoui
et al., 2010). In the Sousse region, Tunisia, lung cancer
represented the most common diagnosed cancer among
Lung cancer has been the most common cancer in
1Research Unit 03/UR/08-13, Cancer Epidemiology and Cytopathology in the Center of Tunisia, Medicine Faculty, 2Cancer Registry
of the Center of Tunisia, 3Pathology Department, Farhet Hached University Hospital, Sousse, Tunisia *For correspondence:
missaouinabiha@live.fr
Abstract

was to describe the epidemiology, pathology and clinical features of lung cancer in Central Tunisia. All lung
cancer cases diagnosed during a 15-year period were analyzed based on the data of the Cancer Registry of the
Center of Tunisia. Five-year age-specific rates, world age-standardized rates (ASR), and annual percent change
were calculated using annual data on population size and the estimated age structure. A total of 1,882 incident
cases of lung cancer were registered (1,782 males, 100 females). The median age at diagnosis was 64 years for
males and 61 years for females, with ASRs of 35.2 per 100,000 among males and 1.5 among females. Over time,
there were significant decreasing trends by -6.5% (95% CI: -12.9%; -0.2%) for females and a stable incidence for
males at an annual rate of +0.2% (95% CI: -1.6%; +1.8%). The predominant histological type was squamous cell
carcinoma in males (36.9%) and adenocarcinoma in females (52%). During 2003-2007, adenocarcinoma became
the most frequent (33.7%) followed by squamous cell carcinoma (30.3%) in males. The majority of tumor cases
were diagnosed at advanced stages (79.9%). In conclusion, lung cancer has remained the most common cancer
diagnosed at advanced stages among Tunisian men. Our findings justify the need to plan and develop effective
programs aiming at the control and prevention of the spread of lung cancer in Tunisia.
Lung cancer is the most common cancer worldwide but data from Tunisia are limited. The aim of this research
Keywords: Lung cancer - incidence - histopathology - advanced stages - Tunisia
RESEARCH COMMUNICATION
Lung Cancer in Central Tunisia: Epidemiology and
Clinicopathological Features
Nabiha Missaoui1,2,3*, Sihem Hmissa1,2,3, Hanene Landolsi1,3, Skander Korbi3,
Wafa Joma3, Affissath Anjorin3, Soumaya Ben Abdelkrim3, Nadia Beizig 3, Moncef
Mokni2,3
men with a world age-standardized incidence rate
(ASR) of 37.1 per 100,000 during 1998-2002 (Curado
et al., 2007). In this paper, we report the burden and
characteristics of lung cancer diagnosed in the Center of
Tunisia during a 15-year period (1993-2007), based on
the database of the population-based Cancer Registry of
the Center of Tunisia.

Materials and Methods

lung cancer diagnosed in the Pathology Department of the
Farhet Hached University Hospital, Sousse and registered
in the Cancer Register of the Center of Tunisia during a
15-year period time (January 1993 – December 2007).
The cancer registry has provided important information
on cancer patterns over the previous years (Parkin et al.,
2003; Curado et al., 2007; Missaoui et al., 2010; Missaoui
et al., 2010; Missaoui et al., 2011). The study was approved
by the Human Ethics Committee at the Farhet Hached
University Hospital of Sousse (Tunisia) and it conformed
We carried out a retrospective study of all cases of

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Nabiha Missaoui et al
to the provisions of the Declaration of Helsinki.
?The?International?Classification?of?Diseases,?10th?
revision?(ICD-10)?was?used?for?cancer?classification?
(Percy et al., 1992). In the present study, the inclusion
criteria were new cases of lung cancer (C33-34) diagnosed
between the 1st January 1993 and the 31st December 2007.
Medical records were reviewed for data on age, origin,
paraclinical data at time of diagnosis, histopathology,
and tumor stage and grade. Histological types were
categorized into three major types: adenocarcinoma
(ICD-O: 8140, 8141, 8200, 8211, 8250, 8251, 8260, 8310,
8323, 8440, 8470, 8480, 8481 and 8490), squamous cell
carcinoma (ICD-O: 8050, 8052 and 8070–8076), small
cell carcinoma (ICD-O: 8041–8045) and the others.
Incidence rates were analyzed during 1993-2007
period. Crude incidence rates (CR) and five-year
age-specific rates were calculated using population
denominators derived as described (Bray et al., 2002;
Curado et al., 2007). ASR were calculated by the direct
method, using the world standard population (Curado et
al., 2007). Rates were expressed per 100,000 person-years
(Curado et al., 2007).
Trends of incidence rates were analyzed during three
periods (1993-1997, 1998-2002 and 2003-2007). The
annual percent change (APC) was calculated as previously
described (Bray et al., 2005; Chen et al., 2006; Missaoui
et?al.,?2010).?In?brief,?the?APC?is?calculated?by?fitting?log-
linear regression line to the natural logarithms of the rates
using calendar year as the independent variable (Bray et al.,
2005).?The?APC?was?obtained?from?the?formula?100?×?[eβ?
-?1],?where?β?is?the?parameter?estimate?obtained?on?fitting?
period of event as a continuous variable to the logarithm
of?the?rate?(Bray?et?al.,?2005).?Statistical?significance?was?
determined?by?calculating?95%?confidence?intervals?(95%?
CI) for the APC (Szklo and Nieto, 2000). In describing
the change, the terms “increase” or “decrease” were used
when?the?rate?ratio?was?statistically?significant?(two-sided?
p values < 0.05); otherwise the term “stable” was used.
Asian Pacific Journal of Cancer Prevention, Vol 12, 20112306
Results
Epidemiology
During the study period, 1,882 patients with lung
cancer?were?identified?accounting?for?10.9%?of?all?cancers?
during the whole 15-year period (1993-2007). The median
age at diagnosis was 63 years with a mean age of 62 years
(ranging from 17 to 92 years). Among our patients, 82.7%
were more than 50 years old (1,557 cases) (Figure1).
In males, lung cancer was accounting for 21.7% of all
cancer cases. The median age was 64 years. The CR was
25.4 per 100,000 and the ASR was 35.2 per 100,000. Over
time, lung cancer remains the most frequent cancer in men
with a stable incidence trend at an annual rate of +0.2%
(95% CI: -1.6%; +1.8%) (Figure 2). Figure 3 shows the
age-specific?incidence?rates?of?the?lung?cancer?during?the?
three periods.
For women, lung cancer account for only 1.4% of
all cancer cases. The median age was 61 years. The CR
was 1.2 per 100,000 and the ASR was 1.5 per 100,000
ranking?the?16th?position.?Over?time,?there?were?significant?
decreasing trends by -6.5% (95% CI: -12.9%; -0.2%).
Pathology and clinic features
The tumor was more frequently located in the right
lung (60.5% versus 39% in the left lung). The disease
was bilateral in only 0.5% of the cases. Upper lobe of the
bronchus or lung was the preferential site of the tumor
(49.5%) followed by contiguous localizations (19.7%) and
the lower lobe of bronchus or lung (17.8%). The tumor
size was higher than 2 cm in 93.3% and than to 5 cm in
67.5%?of?cases.?The?microscopic?verification?(histological?
and cytological method) of diagnosis was 94.6%.
The most represented histological type was squamous
cell carcinoma (35.7%), followed by adenocarcinoma
(27.9%). Small cell carcinoma represented only 15.9%
of tumor cases (Table 1). During the whole 15-year
period, the predominant histological type was squamous
cell carci¬noma in males (36.9%) and adenocarcinoma
in females (52%). The proportion of patients with
adenocarcinomas increased among men during the
study period. The predominant histological type was
adenocarcinoma in males (33.7%) followed by squamous
cell carcinoma (30.3%) during 2003-2007 (Table 2). Grade
III was the most frequent grade (33%) followed by grade
II (32.8%) and grade IV (23.6%). According to the lung
staging system, advanced stages (stage III and IV) were
Figure 1. The Distribution of Patients with Cancer of
the Lung in Central Tunisia, by Age Groups, 1993-2007
0,1
1
10
100
19931995 19971999- 20012003-2005
Year
ASR (per 100,000)
MalesFemales
Figure 2. Trends of the Incidence of the Lung Cancer
in Central Tunisia, 1993-2007
0
50
100
150
200
250
300
350
35-3940-4445-4950-5455-5960-6465-6970-7475+
Age group (years)
Incidence rates (per 100,000)
2003-2007
2002-1998
1993-1997
Figure 3. Age-specific Incidence Rates of the Lung
Cancer Among Males in Central Tunisia During Three
Time-periods

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Lung Cancer in Central Tunisia: Epidemiology and Clinicopathological Features
in France, 49.5 per 100,000 in the United States, 60.0 per
100,000 in Croatia, 71.2 per 100,000 in Poland, and 80.9
per 100,000 in Hungary (Ferlay et al., 2010). Nevertheless,
the incidence rate reported here remains superior to rates
reported from Middle and Western Africa such as Zambia
(ASR: 2.0), Ethiopia (ASR: 2.4), and Somalia (ASR: 2.9)
(Ferlay et al., 2010).
In females, incidence rates were generally lower
than the rates observed among males. Many factors
may?influence?the?differences?in?lung?cancer?incidence?
between men and women. They may be connected with
cigarette smoking, passive smoking, diet, occupation,
indoor exposure and also with host factors that can protect
against or facilitate the development of the cancer (Taioli
and Wynder, 1994; Zang and Wynder, 1996). In Central
Tunisia, the incidence of the lung cancer was only 1.5
per 100,000 women close to that reported in other Arab
regions such us Egypt (ASR:2.5) and Morocco (ASR:
2.1) (Ferlay et al., 2010). The highest incidence rate is
observed in Northern America where lung cancer is now
the second most frequent cancer after breast cancer in
women (ASR: 35.8). In the United States, the lung cancer
ranked the second with an ASR of 36.2 per 100,000 (Ferlay
et al., 2010). The lowest incidence rates in females were
found in the same regions of Eastern, Western and middle
Africa as in the males. The reason for these lower rates in
Africa and the Arab world is still unknown. The problems
facing cancer registry and information gathering in these
two regions are probably one of the reasons in one side
(Salim et al., 2011). Further genetic and environmental
studies remain to be estimated.
The epidemic of cigarette smoking is the major
determinant of past and future lung cancer trends
(Wynder and Hoffmann, 1994; Simonato et al., 2001).
During the last few decades, lung cancer incidence has
stabilized or even exhibited a slow decline among men
in Western countries (Cox and Yesner, 1979; Wu et al.,
1986; Simonato et al., 2001). This observation may have
resulted from effective cancer prevention programs;
especially campaigns against smoking launched in the
second half of the 20th century (Simonato et al., 2001;
B’Chir?et?al.,?2007).?In?Tunisia,?2009?was?the?official?year?
of struggle against smoking as an endorsed campaign
has been organized to sensitize people and raise their
awareness of the dangers of smoking (Ministry of Public
Health, Tunisia).
Carcinoma of the lung is divided into four main types:
squamous cell carcinoma, adenocarcinoma, small-cell
carcinoma and large cell carcinoma (Chung, 1994).
Adenocarcinoma has always been more common in
women than in men, in both smokers and non-smokers
worldwide (Travis et al., 2004). Adenocarcinomas of
lung cancer are more frequent in non-smoking patients,
and they are lower in frequency in Europe than in Asia
or North America (Dosemeci et al., 1997). In Central
Tunisia, squamous cell carcinoma was the most common
histological type in males while adenocarcinoma was the
predominant among females. Our results were close to that
reported from Morocco (Association Lalla Salma de Lutte
Contre le Cancer, 2004) where the predominant type of
lung cancer was squamous cell carcinoma in men (38%)
Table 1. Morphological Aspects of Lung Cancer in
Central Tunisia, 1993-2007
Histological type Males Females Total
Squamous CC
Adenocarcinomas 474 (26.6%)
Small CC
Others
Total
658 (36.9%) 14 (14%)
52 (52%)
8 (8% )
26 (26%)
100 (100)
672 (35.7%)
526 (27.9%)
300 (15.9%)
384 (20.4%)
1882 (100%)
292 (16.4%)
358 (20.1%)
1782 (100%)
CC, cell carcinomas
Table 2. Trends in Histological Types of Lung Cancer
in Central Tunisia, 1993-2007
Histological type 1993-1997 1998-2002 2003-2007
Men (n: 1782)
Squamous CC
Adenocarcinomas 83 (22.4%) 145 (21.3%) 246 (33.7%)
Small CC 66 (17.8%) 113 (16.6%) 114 (15.6%)
Others 59 (15.9%) 150 (22.1%) 149 (20.4%)
Women (n: 100) 26
Squamous CC 4 (15.4%) 9 (26.5%) 1 (2.6%)
Adenocarcinomas 16 (61.5%) 12 (35.3%) 25 (64.1%)
Small CC 1 (3.8%) 4 (11.4%) 2 (5.1%)
Others 5 (19.2%) 10 (29.4%) 8 (20.5%)
371
163 (43.9%) 273 (40%)
681 730
221 (30.3%)
34 39
CC, cell carcinomas
the most frequent (79.9%). Early stages (stages 0 and I)
represented only 4.9% of lung cancer.
Discussion
The current study investigated epidemiology and
clinicopathological patterns of lung cancer in Central
Tunisia diagnosed in the Pathology Department of F.
Hached University Hospital, Sousse (1993-2007). The
cancer of the lung remains the most common cancer
among Tunisian men and constitutes a real problem
of public health. Cigarette smoking is the major risk
factor for the development of this cancer (Wynder and
Hoffmann, 1994; Simonato et al., 2001; IARC, 2004). In
Tunisia, for instance, smoking is responsible for almost
90% all lung cancer cases (Ministry of Public Health,
Tunisia). Nowadays, 1,700,000 smokers aged between 10
and 70 years old amongst whom an annual rate of 7,000
deaths is estimated. A simple equation would show that,
in Tunisia, 20 persons die every day because of tobacco
(Ministry of Public Health, Tunisia). In addition to tobacco
smoke,?many?other?factors?could?influence?individual?
susceptibility to lung cancer in smokers (Lubin and blot,
1984; Travis et al., 1995; B’chir et al., 2007). Among these
are frequently mentioned other carcinogen exposition
from the environment such as air pollution, exposure to
asbestos, arsenic, etc.
In Central Tunisia, lung cancer remains the most
common cancer diagnosed in males. According to
Globocan 2008, the incidence of the lung cancer was of
33.5 per 100,000 men in Tunisia which is widely higher
than the rates observed in other Arab countries such us
Egypt (ASR: 9.6), Saudi Arabia (ASR: 7.2), and Yemen
(ASR: 3.2) (Ferlay et al., 2010). While, the incidence rate
was weaker than the rates observed in Central-Eastern and
Southern Europe, Northern America and Eastern Asia.
For instance, the incidence rates were 47.8 per 100,000

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Nabiha Missaoui et al
and adenocarcinoma (40%) in women. In the Arab Gulf
Cooperation Council countries, squamous cell carcinoma
was also the most frequent cancer in males accounting
for 24.7% followed by adenocarcinoma, whereas
adenocarcinoma was the most frequent histological type
in females accounted to 29% followed by squamous cell
carcinoma (Al-Kawari et al., 2009). While, the study of
Benghazi Cancer registry of Eastern Libya (Benghazi
Cancer Registry, 2004) showed that the overall ratio for
squamous cell carcinomas in both men and women were
higher than adenocarcinomas which accounted for 23%
of all patients with lung cancer.
In the United States, United Kingdom and several
other developed countries, the frequency of different
histological types of lung cancer has changed over the
last two decades so that squamous cell carcinoma has
become less common and adenocarcinoma more frequent
(Devesa et al., 1991; Travis et al., 1995; Janssen-Heijnen
and Coebergh, 2003). In Central Tunisia, the frequency of
adenocarcinoma increased during the last period (2003-
2007) and the squamous cell carcinoma became the second
most frequent histological type after adenocarcinoma
among?men.?These?results?confirmed?the?study?of?B’chir?
et al., (2007). According to the literature, changes in the
types?of?cigarettes?smoked?as?well?as?modifications?in?
time and geographical trends seem to explain partly the
increased incidence of lung adenocarcinoma (Hoffmann
et al., 1991; Wynder and Hoffmann, 1994; Van der Boon,
2001; B’chir et al., 2007). Some authors mentioned that
changes?in?diagnostic?techniques?or?classification?were?
responsible for a major part of adenocarcinoma increase
(Dodds et al., 1981; Charloux et al., 1997; Thun et al.,
1997). The introduction of advances technology such as a
fiber?optic?bronchoscopy?allows?the?access?to?distal?areas?
to the lung. These changes were not observed in most
of the Arab patients with lung cancer except for Qatari
patients (Salim et al., 2011). The sex ratio of lung cancer in
Qatar was 8:1 representing one of the highest ratios in the
world. Adenocarcinomas of the lung in Qatar accounted
for about 44% of all lung cancer subtypes while squamous
cell carcinomas accounted for only 26% (Salim et al.,
2011). Al-Hamdan et al. (2006) showed that only Qatar
had the highest percentage of lung cancer adenocarcinoma
in males than in females (1998-2001). The same data was
confirmed?by?Ibrahim?et?al.?(2010)?who?postulated?that?
lung cancer adenocarcinomas predominated in both male
Qatari natives and expatriates; although the study showed
that a great majority of the patients (82.5%) were current
or ex-smokers at the time of diagnosis.
In conclusion, although the relatively low incidence
rate compared to that reported from developed countries
and the stable incidence trends, lung cancer remains the
most common cancer diagnosed at advanced stages among
men?in?the?Center?of?Tunisia.?Our?findings?justify?the?
need to plan and develop effective programs aiming at
the control and prevention of the spread of breast cancer
in Tunisia.

Acknowledgements
Asian Pacific Journal of Cancer Prevention, Vol 12, 20112308
This work was supported by the Ministry of Public
Health?and?the?Ministry?of?Higher?Education?and?Scientific?
Research in Tunisia.
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