18.1 Tunisia Demographics

With 155,360 km2 (59,985 square miles), Tunisia is the smallest country in North Africa with a population density of 75 people per km2 (195 people per m2) and a Gross Domestic Product (GDP) per capita is at $4341, in 2017 [1]. The country is currently divided into 24 governorates. The most important is Tunis (with more than one million inhabitants), followed by major cities like Sfax and Sousse [1, 2]. Unlike many other North African and Arab countries, Tunisia has led a modern governmental strategy promoting family planning and birth control by Habib Bourguiba, the first President of the country, in the early 1970s. A recent data report indicates a population of about 11.818.61 with a yearly change of +1.06% and a global world rank of 78 [1]. The fertility rate is probably the lowest within Arab countries at 2.2 live births per woman in 2020. In conjunction with a health policy covering the whole country, the famous strategy of family planning revealed a 77.4-year life expectancy (79.3 for females and 75.4 for males) but also an age distribution of 25.2% from 0 to 14 years, 65.8% from 15 to 64 and 8.8% aged 65 years or more. The population median age is 32.7 years old (2020) being 32 in males and 33.3 in females and gender equality is observed between both sexes [1, 2].

18.2 Cancer Statistics in Tunisia

The latest cancer incidence estimates for 2018 are about 15,894 new cases vs 12,189 in 2012, with a standardized incidence of 115/100,000 for the sexes, 131.7 in males and 102 in females [2]. The five most common cancers for both sexes in Tunisia are breast (2305 cases), lung (1909), colorectal (1657), bladder (1323), and prostate with 829 cases. We observed an epidemiologic transition, especially in females with a top position of breast cancer followed by colorectal cancer, while cervical cancer dropped to the third position, probably due to a policy of cervical extended pap smears tests in the primary healthcare centers in parallel with the policy of birth control. In 2018, cancer was responsible for 16.1% of deaths in Tunisia (Figs. 18.1, 18.2, and 18.3) [2].

Fig. 18.1
figure 1

Globocan 2018 cancer cases, whole population and by sex https://gco.iarc.fr/today/data/factsheets/populations/788-tunisia-fact-sheets.pdf [2]

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Fig. 18.2
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Cancer incidence, mortality and prevalence in Tunisia in 2020 https://gco.iarc.fr/today/data/factsheets/populations/788-tunisia-fact-sheets.pdf [2]

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Fig. 18.3
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Epidemiologic data of cancer in Tunisia https://gco.iarc.fr/today/data/factsheets/populations/788-tunisia-fact-sheets.pdf [2]

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As in the Arab world, breast cancer in Tunisia remains by far the most common among females [1, 3]. In a recent series of 1262 Tunisian patients treated for breast cancer, the 5-year overall survival was 72%, while poor-risk factors in the multivariate study were negative HR (P < 0.001) and number of involved axillary lymph nodes were P = 0.023 [4]. A particular kind recognized locally in the country is Inflammatory Breast Cancer (IBC) with Tunisian and North African experience in its diagnosis and management [5]. A study has evaluated breast cancer burden in Tunisia and its impact in terms of adjusted life years (DALY) in 2017 and projections for 2030. The incidence and mortality rate among females in Tunisia was 50.17/100,000 persons per year and 14.04/100,000 persons per year, while breast cancer DALY was at 25,145 (438/100,000 persons per year). Projections for 2030 were at 40071 in 2030 with a standardized rate of 507/100,000 persons per year [6]. Breast cancer in young women, particularly in Tunisia, showed a retrospective study of 83 patients younger than 35 years, treated in Sfax observed a mean age of 31.7 years. They have mostly T2 tumor stage, high histologic grade, and positive axillary node tumors [7]. Overall Survival (OS) at 5 years was 66.8% and poor prognostic factors were CT T3-T4 stages, and several lymph nodes were involved [7].

Lung cancer remains diagnosed at an advanced and/or metastatic stage. In a recent study of 118 Non-Small Cell Lung Cancer (NSCLC) patients, the median age was 43.8 years and 79, 7% of the patients were at an advanced or metastatic stage. Median overall survival was 8 ± 0.72 months [8]. A significant change has been observed in the histological types of lung cancer with an increase of adenocarcinoma over squamous cell carcinoma forms in the last two decades in Tunisia, smoking being responsible for 90% of all lung cancer cases in Tunisia. The evaluation of one study shows tobacco use prevalence was about 25% in the Tunisian population according to a meta-analysis [9]. Tunisia has a higher prevalence of tobacco use, almost 35%, the highest in Arab countries and smokers use cigarettes while traditional sniffed or mouth tobacco has become rare. The number of smokers from 10 to 70 years is estimated at 1.7 million and tobacco is responsible for 7000 deaths per year in Tunisia [9]. Tunisian authorities applied regulatory measures in 2012 prohibiting tobacco advertising on national/international television and radio, local/international magazines and newspapers, billboards, and the outdoors. Nevertheless, there was no toll-free Quitline with a live person to discuss smoking cessation in Tunisia. Nicotine replacement therapy is legally available in the market and could be purchased in a pharmacy with a prescription, but it is not cost covered and is not on Tunisia’s essential drug list. Certainly, informational, and educational campaigns relating to tobacco control should be intensified.

Data from the North Tunisia cancer registry showed 6909 colorectal cancers during the period 1994–2009 with an Age-Standardized Incidence Rate (ASR) raising from 6.4/100,000 in 1994 to 12.4/100,000 in 2009 and a trend in CRC with an Annual Percentage Change (APC) of +3,9%. Projections for 2024 are predicting an ASR of 39.3/100,000 [10]. CRC is rapidly growing but a lot of cases remain diagnosed at advanced stages and even stage II is discussed for an adjuvant medical therapy according to their anatomo-clinical features [11].

18.3 Cancer Risk Factors

The prevalence of Tunisia’s smoking rate in 2016 was 32.70%, a 0.1% increase from 2015 and the rates increased slowly since 2012 [11]. Within a population of 3643 cases of Non-Communicable Diseases, active smoking was found in 1076 cases, accounting for 29.5% of cases [12]. Among the NCD groups, CVD was the most common (65%). Tobacco was significantly associated with CVD (P < 0.001), CRD (P = 0.002), bronchopulmonary CS (P < 0.001), hematological malignancy (P = 0.023), and DM (P < 0.001) in uni and multivariate analyses [12]. Most Arab countries, so as Tunisia, have the common habit of Shisha consumption and, according to a study from Saudi Royal University, based on atomic absorption methods, out of 14.685 mg (heavy) metals present in 1 g of the Jurak paste, only 3.075 μg was transferred to the smoker [13].

Cervical cancer is ranked 15th among females in the country, with a slight decrease probably related to the extensive campaigns of pap smears launched in the primary care structures in the 1970s [14]. Within a screened population of 391 patients from the grand Tunis, overall HPV prevalence was 13.2% and the most prevalent HPV genotypes were HPV6 (40%), HPV40 (14%), HPV16 (12%), HPV52 (9%), HPV31 and HPV59 (7%), and HPV68 (4%), their mean age being 40.7 years. Associated risk factors of HPV infection were smoking (OR: 2.8), low income (OR: 9.6), bad socioeconomic level (OR:2.5), and single woman [15].

18.4 Cancer Screening Programs

In Tunisia, an extensive effort at cervical cancer screening with pap smears based on primary health structures, since the 1970s, led to a down staging of the diagnosed cases [15]. Despite this elementary care effort, there is no primary prevention program like systematic HPV vaccine [16]. There is no structured mammography screening for breast cancer, excluding pilot studies performed in Ariana state in Tunis by the Family Planification Office and another in Sfax [17, 18].

A cancer plan is now running with four axes: training for professionals, clinical and basic research besides the improvement of the quality of care. Biological studies are also concerned with the predisposing factors for breast cancer and nasopharyngeal carcinoma [19, 20].

18.5 Cancer Prevention Programs

Hepatitis B vaccination started in Tunisia in 1995, leading to a slight risk reduction of hepatocellular carcinoma [21]. Multiple units of smoking cessation have been available at university hospitals and pulmonology departments for 20 years [22]. A strict regulation concerning smoking is available in Tunisia, but unfortunately not applied, especially concerning prohibition of smoking in public spaces, and very high taxation concerning tobacco in Tunisia and, currently, Tunisia exerts taxes at a level of 70% on the retail prices of cigarettes [23, 24].

18.6 Cancer Diagnosis

Data from 2014 showed levels for one million inhabitants of MRI at 2, CT scans 8,91, gamma cameras 1.18, Pet-scan, 0, mammography facilities 22. 58, radiotherapy machines 1.64, and Linear Accelerator (LINAC) at 0.64 [25]. However, during the last 2 years, five PET-scans have been available and six LINAC available for stereotactic radiotherapy. Every big Tunisian city has a department of nuclear medicine inside university hospitals (Tunis, Sousse, Sfax, Monastir, Gabes) as well as private centers of nuclear medicine. Translational research is available due to the close collaboration between the researchers from the faculties of sciences and clinicians and the faculties of medicine of Tunis, Sousse, Sfax, and Monastir. Molecular testing is available for leukemia by cytogenetics, BRCA1 and BRCA2, HER2, ALK, EGFR, and ROS1 in both universities and faculties of sciences, as well as private laboratories.

18.7 Treatment

18.7.1 Medical Oncology

Public academic oncology structures are represented by a comprehensive cancer center (Institut Salah Azaiez), oncology and radiotherapy units in university hospitals in Tunis, Sousse, Sfax, Monastir, Jendouba, and medical oncology units in general hospitals in Gafsa, Gabes, Beja, Bizerte, and Sidi Bouzid [1, 3]. Salah Azaiez Institute has the highest recruitment rate with more than 10,000 new patients per year and a structured Multidisciplinary Tumor Boards (MDT) that has disseminated to all the satellite oncology structures created since the year 2000 in Tunis state and other regions. The Medical Oncology Department at Abderrahman Mami hospital in Ariana (SOMA), is inside an oncology center located in a pulmonology hospital. It started initially with only a medical oncology department in 2010, then a radiation oncology department with one Linear Accelerator in 2017. The center recruits about 2000 patients per year, mainly for breast, lung, and colorectal cancers. This oncology hub administers 18,000 ambulatory treatments, a specific Friday devoted to Trastuzumab and other anti-HER2 treatments, other targeted therapies like Beva or Ceuximab, Immunotherapy, 100,000 emergencies, and 15,000 outpatients on average per year. This oncology center coordinated for 3 years, an extended program of translational research combines researchers from the faculty of science of Tunis, Institut Pasteur, and clinicians from university hospitals Charles Nicolle, Abderrahman Mami, Military hospital, and Salah Azaiez, within a program of breast and ovarian family cancers. Medical oncology center in Ariana, Tunisia (the SOMA center) also conducts various social and artistic activities with a program of musicotherapy with and for the patients, with scheduled activities during Pink October. Paramedical and medical staff are around 40 and 20. They are trained with programmed sessions inside the department and at the national level as well as international level, in North Africa and Europe.

18.7.2 Radiation Therapy

There is a need for radiotherapy infrastructure expansion since there are only 21 radiotherapy units in the country (15 Linear Accelerators LINAC, and six Cobalt 60 machines in 5 public hospitals and 7 private clinics) covering less than 46% of the total need [25, 26]. More than 8000 patients undergo radiation therapy on an annual basis with a focus on hypofractionated regimens for breast and rectum cancers to reduce waiting lists. This gap is painfully expressed in very long waiting lists in public hospitals while it remains expensive in the private sector. Therefore, limiting access to the treatment. New RT techniques such as IMRT and Steretacticc radiotherapy (SRT/SBRT) are developed in university hospitals and in private clinics. There is a strategy to stop using Cobalt Units by 2023 which will be replaced with linear accelerators. University departments of radiotherapy are involved in research programms with IAEA and participate in training programms for african countries.

18.7.3 Surgery

Surgical oncology is available at Salah Azaiez Institute, with the highest concentration of surgical oncologists (around 30), having a high experience with breast and gynecologic oncology.

18.7.4 Pediatric Oncology

The facility of pediatric oncology has been available since 1988 at the Salah Azaiez Institute, then in 1995 at Tunis children’s hospital and Sousse and Sfax university hospitals [27]. Most of the oncology teams apply the protocols of the International Society of Pediatric Oncology (SIOP).

18.7.5 Survivorship Track

The available associations that have “on the field” activities of education and patient training for socio-economic sustainability, like housing during treatment. The ATAMCS, devoted to breast cancer and AMC to all cancers, organizes charity and annual events with patients and treating teams (https://jamaity.org/association/association-tunisienne-dassistance-aux-malades-du-cancer-du-sein/ and https://www.facebook.com/AMCTun). There is no specific action concerning cancer survivors.

18.7.6 Palliative Care Track

The palliative cancer treatment initiatives were started in 1988 with the creation of the Tunisian Association for study of pain, which trained in collaboration with Gustave Roussy Institute, medical oncologists for cancer pain diagnosis and management. Since then, 4 units of ambulatory palliative care have been created at Salah Azaiez institute and Sousse and Sfax university hospitals [28].

18.8 Research and Education

In Tunisia, basic research is mostly performed at the faculties of sciences or the biotechnology centers located in the big cities, Tunis, Sousse, Sfax, and Monastir [29, 30]. An effort is needed to increase the collaboration with clinicians in the cancer treatment centers and units as well as recruitment of researchers inside the clinical areas. Cancer education has started for students at the faculties of medicine with hematology-oncology devoted modules and for residents and confirmed physicians, devoted certificates, and masters in thoracic, gastrointestinal, breast, and dermatology oncology.

18.8.1 Breast Cancer Features and Therapeutic Results in Arab Countries

Breast cancer remains late detected due to the absence of mammography screening programs in Arab countries. Anatomo-clinical features are characterized by a younger age at diagnosis (around 50 years, compared to the Western countries, 10% of patients younger than 35 years, 10–13% of initial metastases, and around 17–20% of triple-negative cases and 5% of inflammatory breast cancer (Table 18.1). Five-year overall survival is varying from 70 to 80%.

Table 18.1 Anatomo-clinical characteristics and therapeutic results of breast cancer in Arab countries
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18.9 Cost-Effective Cancer Care

In Tunisia, since 1998, legislation has guaranteed free healthcare for the low-income/unemployed population. Hence, cancer patients with low-income are provided with free healthcare coverage (indigent). Such patients receive treatment in the public sector exclusively. On the other hand, the National Health Insurance Fund (Caisse Nationale d’Assurance Maladie, CNAM) offers insurance for workers and taxpayers treated in the private and public sectors. In Tunisia, there is a universal public healthcare system. Ninety-five percent of the population has governmental coverage to free healthcare access and 80% of the population is treated in the public sector [31]. The private healthcare system in Tunisia has significantly expanded in terms of infrastructure as well as human resources. This sector offers, for example, high-quality cosmetic surgery, spas, and thalassotherapy to attract foreigners, but unfortunately, few patients remain fully covered and mostly must pay their expenses. Every big city has private clinics devoted to cancer treatment, two clinics in Tunis, one in Sousse and two in Sfax. Most of the oncologists have been trained at the Salah Azaiez Institute with the spirit of a multidisciplinary approach and an organ devoted committee for diagnosis and treatment. Globally, patients having social insurance have access to public and private cancer centers, while indigents are covered by the Ministry of Health and Social Affairs. The available patient’s association for cancer in general and breast cancer, provide hospitalizations if needed and help to access therapeutic innovations within donations of administrative sustain.

18.10 Challenges and Advantages

Cytotoxic drugs and targeted therapies are provided to patients covered by social insurance in 55% of cases, while indigent patients (35%) with needs are covered by the Ministry of Health [31]. Usual cytotoxic drugs are covered by the social insurance and for indigents, while targeted therapies like trastuzumab, rituximab, bevacizumab, cetuximab, sunitinib, imatinib, crizotinib, and erlotinib are available only for social insured, with difficulty for indigents, excluding an access program. The entry to therapeutic innovations remains limited due to the high cost of drugs, especially in the absence of approval by ministerial authorities for immunotherapy. Drug prescriptions outlasted slowed by a heavy administrative circuit, installed to reduce, and control the costs of cancer therapies like trastuzumab, bevacizumab erlotinib, erlotinib, and imatinib. The SOMA Oncology Centre adopted a legal approach based on compassionate grounds. This mixed view offers the opportunity to facilitate access to these drugs mainly to Crizotinib, Palbocilib, Ribociclib, and subsequent lines in ALK and EGFR+ lung cancers. Molecular tests are available in public and private structures for ALK, EGFR, ROS1, PD1, BRAF, and RAS and are performed at diagnosis according to the local and international existing guidelines [32].

An effort is being made by the National Agency for accreditation and guidelines (INEAS) to publish guidelines for diagnosis and management of cancer, applicable in both public and private clinics [33, 34]. These efforts were made in collaboration with the Tunisian Society of Medical Oncology (STOM), Radiation Oncology (STOR), and Surgical Oncology (STCO) [33]. There are now almost 100 medical oncologists, 50 radiation oncologists, and 45 surgical oncologists in the public and private sectors.

Tunisian oncologists have robust experience in clinical trials, regulated by a detailed and adapted procedure for more than 20 years [35,36,37]. They have also recognized expertise in specific North African cancers, like Inflammatory Breast Cancer (IBC) and nasopharyngeal cancer [5, 37]. Cancer diagnosis and management requires to be adapted and devoted structures, platforms of histopathology, molecular biology as well as artificial intelligence tools. Tunisian centers remain under-equipped, notably at the molecular biology level. The SOMA oncology center had the opportunity to host a multisite and multidisciplinary study group on breast and family cancer. The group performed huge work on clinical but also translational research with Next Generation Sequencing (NGS), by familiarizing clinical oncologists with basic sciences and translational research [20, 29].

Patients with cancer are at higher risk of being infected with COVID-19 and of developing a more severe form. In China, 1.7% of COVID-19 patients with severe symptoms were found to be cancer patients [38]. The SOMA Oncology Centre is in a university hospital with the most important recruitment of COVID-19 patients, hospitalized in the pulmonology units and the intensive care department. This orientation made the oncologists involved in COVID-19 patient care at the emergency department and the pulmonology units. The oncologists from this unit acquired experience in COVID-19 cases’ detection and management. The oncologists from SOMA cancer center observed more than 20 COVID-19 plus cancer cases, mostly breast cancer, lung, and gynecologic cancers, with two deaths in lung cancer patients. COVID-19 diagnosis was facilitated by easy access to radiologic (chest X-ray and CT-scan) and biologic access with a very close availability of hospitalization beds at Mami Hospital. Strict measures were implemented such as stringent instructions to medical staff and patients about personal hygiene and usage of Personal Protective Equipment (PPE) amongst the clinical staff. All staff and patients have their temperature checked and answer COVID-19 related clinical questions before entering for consultation or treatment administration [39].

18.11 The Future of Cancer Care in Tunisia

The future of cancer care in Tunisia will need important efforts to increase the number of platforms of molecular biology and translational research toward a more innovative and personalized therapeutic approach. The multidisciplinary spirit and approach, following strict national and international guidelines, may warrant better therapeutic results (Fig. 18.4). A structured effort in continuous medical education, at the national, regional, and Arab levels may improve oncologists in terms of Good Clinical Practice (GCP). At the social level, an effort is mandatory to sustain patients and their families, due to the induced “financial toxicity” [47].

Fig. 18.4
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Development of oncology in Tunisia

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18.12 Conclusion

In comparison with other Arab countries, Tunisia is living in a difficult socio-economic and political situation, which combined with the COVID-19 pandemic, increased health expenses, especially for cancer patients. Oncologists are encountering some difficulties in offering their patients modern diagnoses, therapeutic methods, and access to treatment innovations. A regional and international collaboration, especially at the Arab level, could help to perform multicentric epidemiologic and therapeutic studies.