Factors Associated With Esophagus Cancers in Togo, Sub-Saharan Africa

Abstract

Background:

Esophagus cancer is cancer of poor prognosis, of often late diagnosis. The objective of this study was to describe the factors associated with esophagus cancers in the Togolese population.

Methods:

It was a retrospective descriptive, cross-sectional study, on esophagus cancers histologically diagnosed at the Pathological Laboratory of Lomé over a period of 31 years (1990-2021).

Results:

We have collected 144 cases of esophagus cancer. The average age of patients was 57 ± 12 years, and the sex ratio was 2.34. The most applicant service was the service of Hepato Gastroenterology of CHU Campus (30.6%). Alcohol (57.6%), tobacco (45.8%) were the most present risk factors. Biopsies were the most addressed (97.2%). The average duration of symptom evolution was 6.42 months and the main symptom at the time of diagnosis was dysphagia (36.8%). The location of cancer was the lower third for 71.5% of cases. At histology, epidermoid carcinoma was the dominant type (90.3%). Male sex was statistically associated with the occurrence of epidermoid carcinoma and female sex with the occurrence of adenocarcinoma (P < .001). Alcohol, smoking, and consumption of hot foods were statistically associated with the occurrence of epidermoid carcinoma in this study (P < .05).

Conclusion:

Esophagus cancer remains a serious condition for late diagnosis. These are mainly epidermoid carcinomas and having alcohol and tobacco as risk factors. The awareness of the population on the main risk factors would reduce the incidence of oesophagus cancers within the Togolese population.

Background

Esophagus cancer is a malignant proliferation developed at the expense of the various tunics of the esophagus, whether primitive or secondary.^1,2 It is a bad prognosis cancer with high lethality.^{3 -5} With more than 600 000 new cases diagnosed in 2020 worldwide, esophagus cancer is the most common seventh cancer in terms of incidence, responsible for more than 544 000 deaths. ⁶ It is the third digestive cancer in order of frequency after colon and stomach cancer.^{6 -8} Esophagus cancer is characterized by its variable incidence depending on the region and its severity.^5,9 The rates are higher in developing countries than in developed countries for men, but comparable to women. East Asia presents the highest regional incidence rates for men and women, partly because of the large charge in China, followed by southern Africa, East Africa, from northern Europe, and Southern Central Asia. CAP-Vert and Malawi have the highest incidence rates in the world in men and women, respectively.^7,10 Indeed 80% of cases of esophagus cancer worldwide are observed in these countries.^6,11,12

In Africa, several studies report various frequencies, and make it possible to classify this cancer in fourth position of cancers in humans after Kaposi sarcoma, hepatocellular carcinoma, and prostate cancer.^12,13 Excessive consumption of alcohol and tobacco and their synergistic effects are the main risk factors for esophagus cancer in Western countries. ¹⁴ However, in low-income countries, including in certain parts of Asia and sub-Saharan Africa, the main risk factors for epidermoid carcinoma, which generally represent more than 90% of all cases of cancer of the Esophagus have not yet been elucidated, although food components (eg, nutritional deficiencies, nitrosamines) have been suspected. ¹⁵ Other alleged risk factors for epidermoid carcinoma include chewing betel in the Indian subcontinent and the consumption of marinated vegetables (eg, in China) and very hot foods and drinks (eg, in Uruguay, in Iran, and Tanzania). ¹⁴ Dysplasia remains the only useful factor in identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. ¹⁶

In Togo, Darre et al ¹⁷ in a descriptive study on cancers in Togo, had found 52 cases of esophagus cancers, representing 4.2% of all cancers. Bagny et al^18,19 reported 11 cases of esophagus cancer in 11 years while Alassani et al reported an annual incidence of 3.8 cases of esophagus cancers. All these studies have limited themselves to epidemiological, clinical, histological, therapeutic, and evolutionary aspects of this cancer. Thus, we initiated this work whose general objective was to describe the factors associated with esophagus cancers in the Togolese population.

Methods

It was a cross-sectional descriptive study carried out on esophagus cancers histologically diagnosed in the pathological anatomy laboratory of the Lomé University Hospital over a period of 31 years (1990-2021). Togo is a country of 56 600 km², with an estimated population of 7 200 000 inhabitants, located between Ghana in the west, Benin in the east and Burkina faso in the north. Were included all cases of esophagus cancer histologically confirmed. These cases were collected from the registers of this laboratory. Study material consists of biopsies and operating parts set in 10% stamped formalum and was treated according to conventional histology techniques. Variables studied

The variables studied consisted of socio-demographic data including age, sex, the year of diagnosis; clinical data including the seat of the tumor, risk factors, type of symptom, the duration of the symptomatology; as well as anatomopathological data including the type of sample and the histological type of the lesion. All patients with esophageal squamous cell carcinoma were screened for HPV by PCR. PCR was performed using DNA extracted from paraffin-embedded tissue from these patients. Cancer cases were classified according to the 2017 UICC classification (UICC, eighth edition).

Statistical processing and data analysis were carried out using EPI Info software. The results are presented in the form of a proportion for qualitative and average variables and standard deviations for quantitative variables. The Student test was used for comparison of averages, and the Chi-2 test or the exact Fisher test to compare the percentages. The significance threshold was set at .05.

Results

Epidemiological data

We collected 144 cases of esophageal cancers, an annual frequency of 4.64 cases. The average age of patients was 57 ± 12 years, with extremes of 22 and 85 years. These were 101 male subjects, with a sex-ratio (H/F) of 2.34. These patients worked in the informal sector in 105 cases (72.92%). There were not educated subjects in 56 cases (38.88%), and having a level of higher education in 15 cases (10.43%). These cancers sat in the lower third of the esophagus in 101 cases (70.14%) and the average third in 36 cases (25%). Table 1 summarizes the socio-demographic characteristics of the patients. With regard to the existence of risk factors, alcoholism was found in 63 patients and smoking in 16 patients (Table 2).

Table 1.

Socio-demographic characteristics of patients.

	Number	Percentage
Age (years)
20-30	4	2.8
30-40	8	5.6
40-50	24	16.6
50-60	43	29.9
60-70	44	30.5
70-80	18	12.5
80-90	3	2.1
Profession
Informal sector	105	72.92
Official	24	16.66
Pensioner	12	8.33
Student	3	2.09
Level of education
Not attending school	56	38.88
Primary	32	22.22
High school	41	28.47
University	15	10.43
Localization
1/3 Lower	101	70.14
1/3 Middle	36	25.0
1/3 Upper	7	4.86

Table 2.

Distribution of patients by risk factors.

	Number	Percentage
Alcoholism	63	43.75
Smoking	16	11.11
Alcoholism + Smoking	11	7.64
HPV infection	8	5.55
Ingestion of hot food	7	4.86
Ingestion of caustics	5	3.47
Obesity	3	2.08
Alcoholism + HPV infection	3	2.08
Alcoholism + Obesity	1	0.7

Abbreviation: HPV, human papilloma virus.

Clinical data

Dysphagia was found in 53 patients, epigastralgia and hematemesis respectively in 14 and 6 patients (Table 3). The average duration of symptoms evolution was 6.42 ± 3.15 months with extremes of 1 and 15 months. This development duration was 1 to 3 months in 15 patients (10.4%), 3 to 6 months in 43 patients (29.9%), 6 to 12 months in 78 patients (54.2%), and 12 to 15 months in 8 patients (5.6%).

Table 3.

Distribution of patients according to clinical signs.

	Number	Percentage
Dysphagia	53	36.8
Dysphagia and AGC	23	15.97
Dysphagia and epigastralgia	15	10.42
Epigastralgia	14	9.72
AGC and epigastralgia	9	6.25
Dysphagia and vomiting	7	4.86
Hematemesis	6	4.16
AGC and vomiting	6	4.16
Hematemesis, epigastralgia, and AGC	5	3.5
Dysphagia, epigastralgia, and vomiting	3	2.08
Dysphagia, hematemesis, and AGC	2	1.38
Dysphagia, epigastralgia, and AGC	1	0.7

Abbreviation: AGC, altered general condition.

Pathological data

The diagnosis was made on biopsies in 140 cases (97.2%) and on operating parts in 4 cases (2.8%). On the histological level, it was epidermoid carcinoma in 90.3% and adenocarcinomas in 9.7%. These epidermoid carcinomas were well differentiated in 68 cases (48.57%), moderately differentiated and little differentiated in 45 cases (32.14%) and 27 cases (19.29%) respectively. For the 4 cases of operating parts, it was a PT3N0Mx stadium. Male sex was statistically associated with the occurrence of epidermoid carcinoma and female sex with the occurrence of adenocarcinoma (P < .001). Alcohol, smoking and consumption of hot foods were statistically associated with the occurrence of epidermoid carcinoma (P < .05) (Table 4).

Table 4.

Factors associated with esophagus cancers in Togo.

	Histological type			P-value
	Squamous cell carcinoma	Adenocarcinoma	Total
		n = 130	n = 14	n = 144
Gender				<.001
Male	97 (74.6)	4 (28.6)	101 (70.1)
Female	33 (25.4)	10 (71.4)	43 (29.1)
Age (y)				.05
<57	64 (49.2)	5 (35.7)	69 (47.9)
⩾57	66 (50.8)	9 (64.3)	75 (52.1)
Risk factors
Alcoholism				.2
Yes	77 (59.2)	6 (42.9)	83 (57.6)
No	53 (40.8)	8 (57.1)	61 (42.4)
Smoking				.9
Yes	63 (48.5)	3 (21.4)	66 (45.8)
No	67 (51.5)	11 (78.6)	78 (54.2)
Hot food				.8
Yes	50 (38.5)	1 (7.1)	51 (35.4)
No	70 (61.5)	13 (92.9)	93 (64.6)

Discussion

Epidemiological data

There is a geographic disparity in the prevalence and incidence of esophagus cancer.^6,20,21 We have found an annual frequency of 4.64 cases of esophagus cancers. This frequency is greater than those of Bagny et al, Bouglouga et al, and Alassani et al which reported an annual frequency of 1 case, 3 cases, and 3.8 cases respectively.^12,18,19 There is a low incidence of esophagus cancer in West Africa, contrasting with a higher impact in East Africa. ²² Esophagus cancers are higher in developing countries than in developed countries. In fact, more than 80% of esophagus cancer in the world are observed in these countries.^6,7 The cancer of the Esophagus is a cancer of the elderly subject to it our average age of 57 years + 12 and with 75% of our patients being at least 50 years old. This average age is comparable to that of Oumboma et al ¹² which found an average age of 57.08 years. We found a male predominance with a ratio sex of 2.34. Over 70% of esophagus cancers occur in men. ⁶ This male predominance of esophagus cancer is explained by the synergistic effect of a high consumption of alcohol and tobacco in men.^8,23 A high consumption of alcohol was found in 63 patients and an association of alcohol and tobacco consumption in 11 patients. Alcohol, smoking, and consumption of hot foods were statistically associated with the occurrence of epidermoid carcinoma in this study (P < .05). Excessive consumption of alcohol and tobacco and their synergistic effects are the main risk factors for esophagus cancer in Western countries. ¹⁴ However, in low-income countries, including in certain parts of Asia and sub-Saharan Africa, the main risk factors for epidermoid carcinoma, which generally represent more than 90% of all cases of cancer of the Esophagus have not yet been elucidated, although food components (eg, nutritional deficiencies, nitrosamines) have been suspected.^15,24 Other alleged risk factors for epidermoid carcinoma include chewing betel in the Indian subcontinent and the consumption of marinated vegetables (eg, in China) and very hot foods and drinks (eg, in Uruguay, in Iran, and Tanzania). ¹⁴ Dysplasia remains the only useful factor in identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice.^{16,25 -27}

Clinical data

Dysphagia was found in 53 patients, with an average duration of evolution of symptoms of 6.42 months + 3.15. We did not find any statistically significant relationship between the time to evolve the disease and the presence of risk factors (P > .05). This period is clearly higher than that reported by Oumboma et al ¹² which was 2.61 months. Indeed clinically, esophagus cancer remains difficult to diagnose at an early stage. Its initial symptoms are crude, not very specific. At a more advanced stage, dysphagia is considered by several authors as the most common symptom of esophagus cancer.^1,8,20,28

Pathological data

A predominance of epidermoid carcinoma was observed in our series in 90.3% of cases. This predominance of esophageal squamous cell carcinoma was found by Come et al ²⁹ (94.4%).

The geographic variation in the incidence of esophagus cancer differs considerably between the 2 most common histological subtypes (epidermoid and adenocarcinoma carcinoma), which have very different etiologies.^30,31 The incidence of the epidermoid carcinoma of the esophagus in certain high-risk regions of Asia (eg, China) is largely down and may have been preceded by economic gains and food improvements, while in several countries to High income (United States, Australia, France, and the United Kingdom), reductions are considered mainly due to the decrease in smoking.^14,32 Epidermoid carcinoma remains the most common histological type in sub-Saharan Africa.^6,10,12,22

Adenocarcinoma represents about two-thirds of esophagus cancer cases in high income countries, excess body weight, gastroesophageal reflux, and Barrett esophagus being among the main risk factors. ¹⁴ In high-income countries, adenocarcinoma incidence rates therefore quickly increase, partly due to the increase in excess body weight and gastroesophageal reflux, and perhaps because of the decrease in chronic infection levels by H. pylori, which was associated in the opposite way with adenocarcinoma. ³³ These trends should continue in the near future, adenocarcinoma exceeding epidermoid carcinoma in many high-income countries; Excess body weight being likely to contribute more and more to the future load of esophagus cancer.^15,32,34

Molecular data

Esophageal cancer has an aggressive tumor growth and poor prognosis and a 5-year overall survival rate between 15% and 25%. ³⁵ Beyond a certain size, tumors are not further supported by diffusion, but undergo “an angiogenic switch” which supports further tumor growth and metastasis, with formation of new blood vessels within the tumor. ³⁶ Based on that, various cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, are critical in the pathogenesis of numerous cancers. In particular, IL-6 serum levels have been reported to be elevated in patients with esophageal carcinoma, ³⁷ but its role in this cancer remains unclear. IL-6 plays a vital role in cell proliferation, migration, invasion, apoptosis, angiogenesis, growth, and differentiation of cancer cells. ³⁵ Other angiogenic factors involved are vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and fibroblast growth factor (FGF). ³⁵ Several studies indicate that HGF is over-expressed in squamous cell carcinoma tissue specimen and serum levels are associated with survival and clinicopathological parameters such as distant metastases. ³⁸

Genes mutated significantly more frequently in GIAC compared to non-GI adenocarcinomas (non-GIAC) included FBXW7, SMAD2, SOX9, and PCBP1. ³⁶ The frequency of hypermethylation of CpG islets is also significantly higher in GIAC patients than in non-GIAC patients. ³⁶

The role of HPV in esophageal carcinogenesis is a controversial issue that has been described with significant discrepancies in results, which may be attributed to the different methodologies employed in the HPV DNA detection and, in the many ways, in which sample may be collected and preserved ²⁴ and, maybe, the most important, the characteristics of individuals enrolled, including their sexual practices and social-demographic data. ³⁹ Pastrez et al ⁴⁰ demonstrated that the frequency of HPV was identical in the case and control groups (13.8%) using Luminex^® technology.

Limitations

Our study has the limitations common to all retrospective studies. Some information was not always found, in particular the existence of risk factors, the status of lymph node invasion and metastases. Our study only took into account biopsies received and studied at the pathological anatomy and cytology laboratory of the CHU Sylvanus Olympio, a functional institution in the country, which sometimes has difficulty in draining all the samples, particularly those from the interior of the country. It was also difficult to obtain information on patient survival, which could have enabled us to highlight the often very poor prognosis of these esophageal cancers in our context.

Conclusion

Esophagus cancer is poor prognosis cancer often diagnosed at a late stage. It is the most common seventh cancer in terms of incidence and the third digestive cancer. The synergistic effects of alcohol and tobacco consumption remain the main risk factors for epidermoid carcinoma, which represents the main histological type of esophagus cancers in sub -Saharan Africa. A control of these main risk factors, by setting up a population awareness system; would reduce the incidence of these cancers in the Togolese population.