Based on the calculation of the sample size, 65 patients with head and neck cancers were enrolled into the study while 65 healthy participants were enrolled as controls.
40 4.8.1 Data analysis
Data obtained was recorded and analysed using the Statistical Package for Social Sciences (SPSS) version15.
Demographic variables were represented using tables and charts while summary statistics were done using means and proportions. The differences in socio-demographic characteristics between cancer cases and controls were compared using t test for quantitative variables and chi square for qualitative variables. The difference in zinc levels between the groups were tested using t-test and Mann Whitney U test if the distribution of zinc levels was skewed. The comparison of zinc levels at different stages of disease was done using the Analysis of variance and kruskal Wallis tests respectively for normal and skewed data. Analysis of covariance was used to adjust for differences in baseline characteristics in the comparison of zinc levels between cases and controls. .
The level of statistical significance was set at p value <0.05.
41 Chapter V Results 5.1 Demography
Sixty five patients with HNSCC participated in this study and 65 healthy participants constituted the control group. There were 39 (60%) males and 26 (40%) females giving a male to female ratio of 1.5: 1. The control group had identical male and female distribution.
The age range of the cases was 15 to 84 years with a mean age of 50.92 and standard deviation (SD) of 15.20. The age range of the controls was 17 to 82 years and the mean age of the control group was 49.49 with standard deviation of 16.35.
Majority (49.2%) of the patients with HNSCC belonged to the low income and low educational group (Socioeconomic class V) while 36.9% belonged to the socioeconomic class II. There is a wide disparity between the high income group and the low income group with few of the participants belonging to the middle income earning group. The control group had similar socioeconomic class distribution. This is shown in figure 1.
Fig 1: Bar chart showing socio-economic status among cases and controls
42 5.2 Anatomical sites of HNSCC
Nasopharyngeal and the sinonasal regions were the sites most frequently involved in this disease. They each constituted 29.2% of the cases seen. One (1.5%) patient had Squamous cell carcinoma of the right parotid gland. The distribution of the anatomical sites of this disease is shown in table 1.
Table 1: Anatomical sites of Head and Neck Cancers
Sites Frequency (N)
Percentage (%)
Larynx 17 26.2
Nasopharynx 19 29.2
Sinonasal 19 29.2
Parotid gland 1 1.5
Hypopharynx 2 3.1
Oropharynx 5 7.7
Middle ear 2 3.1
Total 65 100.0
Stage IV disease was the most common stage at presentation with thirty-six (55.4%) patients presenting in this stage. Two patients presented in stage I. The stages of the disease and the frequency of presentations are shown in table 2.
43
Table 2 Anatomical sites and disease stage at presentation
Site I II III IV Total
Larynx 1 0 9 7 17
Nasopharynx 0 4 1 14 19
Sinonasal region 1 2 5 11 19
Parotid gland 0 0 0 1 1
Hypopharynx 0 1 0 1 2
Oropharynx 0 1 2 2 5
Middle ear 0 0 2 0 2
Total N (%) 2 (3.1) 8 (12.3) 19 (29.2) 36 (55.4) 65 (100.0)
5.3 HNSCC and Nutritional status
According to the Body Mass Index (BMI), sixteen patients (24.6%) with HNSCC were underweight while 21 (32.3%) patients had weight in excess of their height. This gives a total of 37(56.9%) patients with malnutrition. The control group had a higher number of participants with normal BMI (58.5%) and lower number of underweight participants (12.3%).
The distribution of the weight classes of both groups is shown in table 2. The comparism is further depicted in figure 2.
There are descriptive differences in the two groups with the controls appearing to have better nutritional status than the cases however, on the average; this is not statistically significant (p= 0.524) as shown in table 3.
44 Table 2: BMI of the cases and the controls
Nutritional Status
Cases Controls
N (%) Range Frequency Range
Underweight 16 (24.6) 15.5 – 18.3 8 (12.3) 15.5 – 18.2
Normal 28 (43.1) 18.9 – 24.5 38 (58.5) 19.2 – 24.5
Overweight 17 (26.2) 25.0 – 29.8 17 (26.2) 25.0 – 29.4
Obese 4 (6.2) 30.9 – 38.6 2 (3.1) 31.6 – 36.7
Total 65 (100.0) 65 (100.0)
45
Figure 2: Bar chart showing Nutritional status among the cases and controls
0 10 20 30 40
UW NM OW OB
Cases Control
*UW= Underweight, NM= Normal weight, OW= Overweight, OB= Obese Table 3: Statistical difference between the BMI of Cases and Controls.
Cases Mean ±SD
Control Mean ± SD
Df CI p-value
Body Mass
Index (BMI)
22.66 ± 4.70 23.14 ± 3.8 128 -1.965 – 1.00 0.524
The anthropometric parameters did not reveal any statistically significant differences in the nutritional status among the disease stages in the case group. The weight (p=0.69), BMI (p=0.518), mid arm circumference (p=0.146) and waist circumference (p=0.062) did not differ significantly among the disease stages.
A similar observation was made in the nutritional status using the biochemical parameters of total serum protein (p=0.22), serum albumin (p=0.797) and serum zinc (p=0.95).
46 These are shown in tale 4 and 5 below.
Table4: Relationship between tumour stage and Nutritional status using Anthropometric measurements.
Stage I Mean (SD)
Stage II Mean (SD)
Stage III Mean (SD)
Stage IV Mean (SD)
p-value
Age (years) 58.00±7.07 52.50±20.83 59.21±12.22 45.81±13.79 0.013 Weight (kg) 71.50±12.02 68.13±9.70 62.61±12.04 63.90±15.35 0.691 Height (M) 1.63±0.02 1.70±0.84 1.67±0.10 1.69±0.09 0.522 BMI(kg/m2) 27.13±5.28 23.58±3.46 22.36±3.12 22.37±5.55 0.518 MAC (cm) 32.50±2.12 28.50±3.85 26.53±3.27 27.09±4.00 0.146 WAC (cm) 99.50±14.85 83.25±7.70 79.00±8.73 80.12±11.52 0.062
Table 5: Nutritional status and disease stage using Biochemical parameters
Stage I Mean (SD)
Stage II Mean (SD)
Stage III Mean (SD)
Stage IV Mean (SD)
p-value
Serum protein g/dl 8.05±0.49 7.8±0.31 7.28±0.73 7.25±0.87 0.224 Serum albumin g/dl 3.75±0.78 3.96±0.43 3.84±0.49 3.73±0.64 0.797 Serum zinc level µg/dl 95.74±23.07 90.28±12.05 89.51±15.83 89.59±14.05 0.949
47 5.4 HNSCC and Serum Zinc:
Two (3.1%) patients with advanced nasopharyngeal cancer had serum zinc levels below the reference value of zinc (Laboratory reference values 70 - 120µg/dl). There was no significant difference (p=0.95) among the different stages of the disease as shown in table 5 above. The participants in the control group had serum zinc levels that were within the reference range.
In comparing the serum zinc levels of the cases and controls, the control group had statistically significant (p=0.00) higher zinc levels in all the weight classes except in the obese (p=0.25) as shown in table 6.
Table 6: Difference in the mean serum Zinc levels between cases and controls of different nutritional status
Mean SD CI Df p-value
Underweight Cases Control
82.42±17.19 116.63±4.03
-43.72 – (-24.69) 22 0.00
Normal Cases Control
89.98±12.86 112.98±6.54
-28.37- (-17.63) 64 0.00
Overweight Cases Control
92.16±9.73 113.21±5.67
-26.67 – (-15.44) 32 0.00
Obese Cases
Control
108.66±8.93 117.73±1.76
-27.78 – 9.65 4 0.25
48
Overall, the mean serum zinc level of the healthy participants was significantly higher statistically than that of patients with Head and Neck Squamous cell Carcinoma (p=0.000) as shown in table 7.
Table 7: Difference in the average serum zinc levels between the case and control groups
Cases Mean ±SD
Controls Mean ±SD
Df CI p-value
Serum Zinc levels
89.84±14.27 113.63±6.04 86.2 -27.62 – (-19.97) 0.00
49 Chapter VI Discussion
Sixty five patients with HNSCC participated in this study. Globally there are approximately 550,000 cases of head and neck cancers every year.85 Head and neck cancers account for 3 percent of malignancies in the United States with an estimated 52,000 Americans developing it and 11,500 dying from it annually.86 Thirty eight cases annually were reported in Lagos87, Ile-Ife reported 31cases88 while 47 cases of head and neck cancers were reported annually from Jos.89
An average of 62 cases was seen annually in retrospective studies done in University College Hospital (UCH), Ibadan.90, 91 However; these studies included all types of head and neck malignancies. Patients with HNSCC diagnosed in UCH as well as those already with histologic diagnosis referred from other centres were recruited in this study. This perhaps would account for the seemingly higher number of cases seen in this study.
Head and neck cancers in general have a male preponderance and findings in this study corroborated this. A male to female ratio of 1.5:1 was seen. This ratio is slightly lower than that reported from China and Japan where a ratio of 2.4:1 was reported in 19 and 13 year study respectively.92, 93 Abuidris found a ratio of 1.7:1 in Central Sudan.94 In a meta-analysis of 27 relevant published articles on head and neck cancers in Nigeria from 1968 to 2008 a male to female ratio of 1:1 to 2.3:1 was revealed.95
These various studies considered all head and neck malignancies together however; specific anatomical sites may provide a clearer picture of the male to female ratio. Fasunla et al.96 reported a male to female ratio of 2.15:1 in patients with sinonasal malignancies. Amusa et
50
al.97 observed a ratio of 12:1 for laryngeal cancers while Nwaorgu et al98 reported 2.3:1 for nasopharyngeal cancers.
The mean age seen in this study was 50.9years (SD ± 15.20). This is slightly higher that had reported by Adisa et al91 where a mean 43.9years (SD ± 19.3) was reported for all head and neck malignancies seen in their 19 year retrospective study.91 Their study however also consisted of paediatric age group. The mean age seen in this study is similar to the mean age of 48.1years of patients with HNSCC in the retrospective study by Adisa et al.91 This may be due to the fact that HNSCC peaks in the 5th decade of life (40-49years).99 Similar mean age has been reported from central Sudan.94
Individuals with low income as well as low education (socioeconomic class V) constituted the largest group (49.2%) of patients with HNSCC. Regarding the global incidence of head and neck cancers, 60% of cases have been reported to occur in developing countries1 especially among the economically disadvantaged indigenes.1 These individuals are wont to abuse alcohol and tobacco and also posses poor dietary habits as well as poor oral and personal hygiene1. Individuals belonging to the low socioeconomic class also have poor health seeking behaviour as they are less likely to be aware of screening programmes for HNSCC.100 The preponderance of patients with HNSCC in the low socioeconomic status seen in this study is in consonance with the findings by Al-Dakkak in the United Kingdom.101 He found that a higher risk of head and neck cancer (HNC) was consistently associated with poor socioeconomic circumstances. However, when adjustments were made for alcohol consumption and tobacco smoking, the statistical significance was lost.101
51
Conway et al did not find a change in the statistical significance of this risk when adjustments were made for smoking, alcohol consumption and dietary behaviours in their own study.102 This study also corroborates the increased incidence of this heterogeneous group of diseases among the low socioeconomic class reported by other authors in this environment.89, 103, 104 In contrast however, there was no significant difference in the distribution of oral Squamous cell carcinoma in the high socioeconomic and low socioeconomic classes in Ibadan, Nigeria.103 These patients had no significant exposure to tobacco smoking, alcohol consumption or both.103
The nasopharynx (29.2%) and sinonasal (29.2%) regions accounted for the commonest anatomical sites of HNSCC seen in this study. The larynx was next with 26.2% of the cases seen. The predilection of these tumours for the upper respiratory tract is in consonance with the overall pattern seen in Nigeria with the nasopharynx, nose and larynx being the commonest sites affected in descending order.91, 95 In central Sudan the upper respiratory tract constituted 72.7% of the sites of head and neck cancer.94 Amusa et al.88 however reported oral cavity as the commonest site in their study. Children with Burkitt’s lymphoma of the jaw were grouped into oral cavity tumours in their study.88 This may explain the reason for the increase in the site.
The nasopharynx was the commonest site in 19,400 patients with malignant tumours of the head and neck in Guagnxi province in China.105 Consumption of smoked salted fish was implicated as the predisposing factor.106 It has been postulated that perhaps the wood smoke in ill ventilated houses, wood dust, and Epstein Barr virus infection may be the predisposing factor for this predilection of this disease for the upper respiratory tract in Africans.107
52
Majority (84.6%) of the patients seen in this study presented in advanced disease stage (stage III [29.2%] and stage IV [55.4%]). This is similar to the findings by Elumelu et al.104 where 81 out of 100 patients seen in their study presented with advanced disease.104 Similar reports were made from Ile-Ife and North Eastern Nigeria.97, 108
The larynx and maxillary sinus were the sites involved in stage I disease. The patient with laryngeal cancer presented early because her symptom (unremitting hoarseness) was affecting her ability to relay messages at work while the patient with left maxillary antral carcinoma presented early due to recurrent unilateral Epistaxis respectively. Evaluation of the paranasal sinuses with a computed tomogram revealed the mass in the lateral wall of the antrum. This patient belonged to the high socioeconomic class (class I).
Several studies done in this environment have shown that late disease stage presentation of these patients could be attributed to the socio-cultural beliefs and misconceptions which have led to the patronage of alternative medical practitioners even by highly educated and enlightened patients of the people.109 Other contributing factors to late presentation include ignorance, local taboo, poverty and poor recognition of the disease condition by primary health providers.97, 110, 111
Sixteen patients (24.6%) with HNSCC were found to be underweight in this study. This is similar to other studies where 20-30% of patients with HNSCC were found to be malnourished.112, 113 Anthropometry, especially weight changes have been shown to be the most reliable indicators of nutritional status in patients with HNSCC. Poor nutritional status in head and neck cancer patients has been shown to have a negative effect on the course of the disease, the ability of the patients to withstand the various treatment modalities, hospital stay and overall prognosis. Therefore it has been advocated that early nutritional intervention
53
at the time of diagnosis must be commenced and it must continue during treatment and after discharge.114
Twenty one (32.3%) patients with HNSCC were found to have Body mass Index above normal (overweight [24.6%], obese [7.7%]). Obesity has been implicated as a predisposing factor to the development of cancers in various parts of the body.115, 116 In head and neck cancers obesity has been shown to cause a delay in the institution of nutritional rehabilitation as the patients tend to be misidentified as having adequate nutrition.112 Gaudet et al117 made a different observation regarding obesity and HNSCC. They observed that a BMI of 25kg/m2 and above conferred significantly higher survival rates for patients with HNSCC than those with lower BMI. However this association was found only in patients with a history of tobacco use.117
The control group had a higher proportion of participants with adequate weight (58.5%), fewer underweight (12.3%) and obese (3.1%) participants when compared with the cases.
Descriptively the control group appears to be better nourished than patients with HNSCC.
However, on the average, this was not statistically significant (p = 0.52).
There was no statistically significant difference in the nutritional status in the case group among the different disease stages. This was observed in the anthropometric parameters as well as the biochemical indices (p>0.05). This is in contrast with the study done by Luis et al.118 They found a statistical significant difference in the nutritional status among patients at different stages of the disease. The patients in advanced disease stage (III and IV) were more malnourished when compared with those with less advanced disease.118 This is not the case in this present study even though, using the mean weight values for the different disease stages, descriptively/numerically that the BMI of the early disease stage is higher than that of the late stage.
54
The serum protein and albumin levels of the patients were within the reference range in all but two patients with advanced nasopharyngeal carcinoma and one patient with advanced sinonasal tumour (all had moderately depleted albumin levels). Marked changes in serum albumin were not observed in this study. This may be due to the fact that albumin has a long half life (approximately 20 days) and therefore does not detect early protein depletion.
The two patients with advanced nasopharyngeal cancer also had zinc serum levels below the laboratory reference values. Serum zinc levels have been reported to be better prognostic indicators than serum protein and albumin levels in patients with HNSCC.4 The role of zinc in HNSCC has been extensively studied.
There was no statistically significant difference in the serum zinc levels among the different disease stages in the patients with HNSCC (p = 0.95). However, when compared with the levels in the control group, the results show that within each nutritional status group, the zinc levels of the cases were significantly lower than the zinc levels of the controls within the same nutritional status group (p = 0.00) except in the obese where there is no significant difference between the zinc levels of the cases and the controls (p = 0.25).
The absence of significance in the obese group may be due to the fact that the number of individuals in this group is too few for accurate computation or perhaps obese patients with head and neck cancers are able to maintain serum zinc levels that are close to that of healthy individuals for a longer period.
On the average, serum zinc levels were found to be significantly higher in the 65 healthy participants than in the 65 patients with HNSCC seen in this study (p = 0.00). This is in consonance with studies done in other regions where zinc deficiency was associated with local recurrence in stage III and IV disease72, and worse prognosis in patients with HNSCC.77,
80
55
Conclusion:
The anatomical sites of HNSCC and disease stage at presentation are similar to other studies seen in this country.
The nutritional status of patients with HNSCC did not appear to differ significantly with advanced disease stage.
Only two patients with HNSCC had zinc deficiency. However their serum zinc levels were significantly lower than that obtained in healthy individuals.
While this result would suggest that there is an association between this disease and reduced serum zinc levels, it cannot be stated that reduction of this vitamin is a risk factor for this disease.
Further research into the dietary habits and adequacy of Zinc intake in the diet of the general population is required to determine if relative depletion of this trace element is a predisposing factor to an increased incidence of this disease in our environment.
56 Chapter VII
RECOMMENDATION
The nutritional status of patients with HNSCC must be adequately assessed at presentation and early intervention must be commenced. The involvement of Nutritionists and Dieticians must be as early as possible. Zinc supplements should be commenced in patients with HNSCC from the first contact. Public awareness about the early symptoms of Head and Neck cancers must be increased and their health seeking behaviours must be improved. This can be achieved through health awareness programs in schools, media houses and in the religious houses.
Health education on diet with special emphasis on foods containing zinc and other trace elements must be carried out in schools and various media houses.
A screening program to detect low serum zinc levels in individuals at risk of poor nutrition should be instituted and the supplements commenced to reduce the risk of developing head and neck cancers.
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