Keywords
head and neck neoplasms - trend analysis - diagnostic delays - histopathology - Saudi
Arabia
Introduction
Head and neck neoplasms (HNN) include a heterogeneous group of tumors, both benign
and malignant predominantly affecting the upper aerodigestive track.[1] In the United States, head and neck cancer accounts for 3% of all cancers.[2] Based on the data collated and compiled at the International Agency for Research
on Cancer, anatomical sites including the lip, tongue, and mouth with 355,000 newly
diagnosed cases per year could be considered to carry a high proportion of head and
neck cancers.[3] Among the head and neck cancers (HNC), the epidemiology of oral cancer has almost
exclusively been studied in Saudi population where risk factors vary widely in different
regions.[4]
[6] However, very little is known about the magnitude of the risk factors, morbidity
and mortality of HNN (benign and malignant) in Saudi Arabia.[6] In the context of different geographic locations, knowledge about the HNN distribution
and its variability within certain community profile (i.e., gender and age) is an
essential prerequisite. The current literature elucidates noticeable regional differences
in patterns of incidence of HNN in Saudi Arabia.[7]
[10] This geographic variation could be attributed to cultural differences and associated
risk factors.[11] Availability of such data can help in prioritization and provision of population-specific
healthcare services, implementation of preventive strategies, and distribution of
resources according to specific population needs.[12]
Saudi Arabia is one of the largest Arab countries of the Arabian Peninsula that is
divided into 6 regions and 13 provinces.[13] The highest incidence rate of HNC (oral cancer) was reported in the southern province
of Jazan, Saudi Arabia. In Jazan, oral squamous cell carcinoma is currently the most
common malignancy diagnosed in females and second-most common in males.[14] Use of smokeless tobacco (shamma) has been a recognized risk factor for the high
incidence of oral cancer in women in this region.[14] In another study, by Al-Zahrani et al, investigating outpatient palliative care
at a major tertiary hospital in Saudi Arabia, HNC was the second most common cancer
among patients (15.3%).[5] However, in the northern region, benign conditions were diagnosed more frequently
than malignancies.[9] Al-Madinah Province is located in the western region of Saudi Arabia, with a population
of 2,132,679.[13] Since 2009, King Fahad Hospital in Al-Madinah City is the only specialized referral
center that offers free oral and maxillofacial consultative and diagnostic services
throughout Al-Madinah Province and other peripheral hospitals in the region. The hospital
offers aforementioned healthcare services to all patients that minimizes access bias
contributing to greater accuracy on the incidences of neoplasms in this region. Due
to the lack of information regarding the prevalence of HNN in Al-Madinah Province,
the present study aimed to present data on HNN prevalence with specific focus on sociodemographic
determinant in Al-Madinah Province, Saudi Arabia.
Materials and Methods
Study Design and Subjects
This was a retrospective study based on the primary data retrieved from the archives
of the Oral and Maxillofacial Pathology Laboratory at King Fahad Hospital in Al-Madinah
City.
All cases with confirmed histopathology analysis of a HNN (ICD-10: C00-C44, D00-D23)
over a period of 6 years (2012–2018) were included in the study. Patients who were
diagnosed with jaw cysts, inflammatory lesions, reactive lesions, or those with no
histopathological diagnosis were excluded.
Data Collection
The data collection sheet was designed by Microsoft Office Excel 2016 to enter information
from King Fahad Hospital’s archives. All data were collected and checked by two investigators.
Electronic search was generated first, then manual extraction of the data was done
to make sure no data were missed. A temporary user platform was created by the hospital’s
IT department with restricted access to identifiable health information for protection
of patients' privacy. Other information included the following: demographic data (sex,
age and nationality), date of admission to the hospital with length of stay, preoperative
diagnosis, histological diagnosis, and biopsy site. Data related to presence of multiple
lesions of a patient was recorded based on the history of recurrent lesions or two
or more lesions on different sites of the same patient. All of the biopsies were performed
by oral and maxillofacial surgeons and submitted for histopathological examination
by certified general pathologists at King Fahad Hospital.
Data collection sheet involved two parts: the first part was a collection of demographic
data and preoperative diagnoses, including all patients with lesions, tumors, neoplasms,
cancer, and some metastasized conditions. The second part was a collection of final
histopathological diagnoses according to the biopsies undertaken. Both incisional
and excisional biopsies were included, and if the same patient had an incisional and
excisional biopsy, the excisional biopsy was counted. Sociodemographic differences
between malignant (C00-C44) and benign (D00-D23) neoplasms were assessed. The anatomic
sites were further categorized into the four most common locations; the other locations
were grouped under “others.”
Statistical Analysis
The data were imported from Excel Sheet into the Statistical Package for Social Sciences
(SPSS Inc., Chicago, Illinois, United States) version 20 for analysis. Descriptive
analysis was performed to report the demographic variables of the patients. Means
and standard deviations were reported for the continuous variables with normal distribution,
and as median and Interquartile when no adherence to normality was observed (Kolmogorov–Smirnov,
p < 0.05). Frequencies and percentages [F(%)] were used for categorical variables.
An independent t-test and/or nonparametric (Mann–Whitney U test, chi-squared test) tests were used
to determine the differences between groups. Statistical significance was set at the
p-value < 0.05.
Ethical Consideration and Confidentiality
The protocol for the study was approved by Taibah University’s Dental College Ethical
Research Committee (IRB approval no. TUCDREC/20170920/Alsharif) and the Ministry of
Health (approval no. IRB-116), Al-Madinah, Saudi Arabia. Due to the retrospective
nature of the study, patients' informed consent was not required. However, confidentiality
of the information was assured, that is, every patient was assigned a code.
Results
Patients’ Characteristics
Out of 96 patients, a total of 58 patients had valid biopsy data with preoperative
diagnosis and final histopathology diagnosis of a HNN. A total of 58 HNN cases met
the inclusion criteria. [Table 1] shows the characteristics of the subjects: the majority (70%) were of Saudi nationality
with a slight male predominance (56.9%). The mean age of the patients was ~39 ± 19
years old. Multiple head and neck lesions were found in four (6.9%) of the subjects.
On average, the patients remained in the hospital for 3 days after undergoing a biopsy.
[Table 1] also shows that 9 patients (15.5%) were readmitted to King Fahad hospital after
being discharged.
Table 1
Characteristics of patients with head and neck neoplastic lesions (n = 58)
|
Characteristics
|
Frequency (%)
|
|
Abbreviation: IQR, interquartile range.
|
|
Gender
|
Males
|
33 (56.9)
|
|
Females
|
25 (43.1)
|
|
Nationality
|
Saudi
|
40 (69)
|
|
Non-Saudi
|
18 (31)
|
|
Multiple sites
|
Yes
|
4 (6.9)
|
|
No
|
54 (93.1)
|
|
Readmission
|
Yes
|
9 (15.5)
|
|
No
|
49 (84.5)
|
|
Length of stay (d)
Median (IQR)
|
3 (4.3)
|
[Table 2 ]also illustrates that males were more likely to be diagnosed with a benign tumor
than females (54.5 vs. 45.6%, respectively), and malignancy was also more common in
males (64.3 vs. 24.1%). The mean time between the first examination and final diagnosis
for all lesions is found in [Table 2]. The average time frame of “door to diagnosis” for patients diagnosed with benign
lesions was ~42.3 ± 67.7 days and for malignant 29.9 ± 30.8 days.
Table 2
Distribution of head and neck neoplasm based on lesions (n = 58)
|
Head and neck lesions
|
n(%)
|
Gender, n (%)
|
Age range/years
|
|
Male
|
Female
|
|
Abbreviation: SD, standard deviation.
|
|
Benign neoplasms
|
|
Pleomorphic adenoma
|
7 (12.1)
|
3 (42.9)
|
4 (57.1)
|
24–59
|
|
Ossifying fibroma
|
7 (12.1)
|
4 (57.1)
|
3 (42.9)
|
6–36
|
|
Ameloblastoma
|
5 (8.6)
|
4 (80)
|
1 (20)
|
28–60
|
|
Warthin tumor
|
4 (6.9)
|
2 (50)
|
2 (50)
|
26–81
|
|
Odontogenic myxoma
|
4 (6.9)
|
3 (75)
|
1 (25)
|
14–26
|
|
Acquired melanotic nevus
|
2 (3.4)
|
2 (100)
|
0 (0)
|
35–63
|
|
Central giant cell lesion
|
2 (3.4)
|
1 (50)
|
1 (50)
|
17–35
|
|
Squamous papilloma
|
2 (3.4)
|
2 (100)
|
0 (0)
|
27
|
|
Lipoma
|
2 (3.4)
|
1 (50)
|
1 (50)
|
41–53
|
|
Cementoma
|
1 (1.7)
|
0 (0)
|
1 (100)
|
57
|
|
Solitary fibrous tumor
|
1 (1.7)
|
0 (0)
|
1 (100)
|
64
|
|
Pilomatricoma
|
1 (1.7)
|
0 (0)
|
1 (100)
|
5
|
|
Lobular capillary hemangioma
|
1 (1.7)
|
0 (0)
|
1 (100)
|
40
|
|
Cavernous hemangioma
|
1 (1.7)
|
0 (0)
|
1 (100)
|
10
|
|
Unspecified benign neoplasm
|
4 (6.9)
|
2 (50)
|
2 (50)
|
25–54
|
|
Total (%)/mean ± SD
|
44 (75.9)
|
24 (54.5)
|
20 (45.6)
|
5–81
|
|
Malignant neoplasms
|
|
Squamous cell carcinoma
|
5 (8.5)
|
2 (40)
|
3 (60)
|
36–66
|
|
Mucoepidermoid carcinoma
|
3 (5.2)
|
3 (100)
|
0 (0)
|
17–62
|
|
Metastatic carcinoma
|
2 (3.4)
|
1 (50)
|
1 (50)
|
79–81
|
|
Osteosarcoma
|
1 (1.7)
|
0 (0)
|
1 (100)
|
28
|
|
Malignant neoplasm of maxillary sinus
|
1 (1.7)
|
1 (100)
|
0 (0)
|
61
|
|
Non-Hodgkin lymphoma
|
1 (1.7)
|
1 (100)
|
0 (0)
|
69
|
|
Verrucous carcinoma
|
1 (1.7)
|
1 (100)
|
0 (0)
|
57
|
|
Total (%)/mean ± SD
|
14 (24.1)
|
9 (64.3)
|
5 (35.7)
|
17–81
|
Tumors’ Sites and Trend Over Time
As shown in [Fig. 1], the most frequently affected anatomical site was the mandible (n = 19, 32.8%), with 94.7% of benign lesions followed by the parotid gland (n = 9, 15.5%), palate and facial skin (n = 5, 8.6%).
Fig. 1 Distribution of head and neck tumors based on anatomic location.
Trend analysis of the data commencing in 2012 showed an increased incidence of head
and neck neoplastic lesions in 2013/14 ([Fig. 2]), with subsequent gradual decline in prevalence. A sharp increase in the number
of new cases was observed from 7 cases to 15 cases per year from 2016 to 2018 but
regarded statistically nonsignificant (p > 0.05).
Fig. 2 Incidence for head and neck neoplasms over the period 2012 to 2018.
Bivariate Analyses of Factors in Relationship to Malignant and Benign Lesions
In bivariate analyses, some of the variables revealed statistically significant differences
(p < 0.05) in relation to lesion diagnosis ([Table 3]). A significant difference was found in relation to mean age of older patients who
were more likely to be diagnosed with malignant tumors (p = 0.001). The hospital stay of patients with malignant lesions was extended beyond
that of those with benign lesions (p = 0.016).
Table 3
Characteristics and bivariate analysis results of comparisons of patients with benign
(n = 44) and malignant lesions (n = 14)
|
Patients’ characteristics
|
Diagnosis: n (%)
|
p-Value
|
|
Benign lesion
|
Malignant lesion
|
|
Abbreviation: SD, standard deviation.
|
|
Gender
|
Males
|
24 (72.7)
|
9 (27.3)
|
0.52
|
|
Females
|
20 (80)
|
5 (20)
|
|
Nationality
|
Saudi
|
32 (80)
|
8 (20)
|
0.27
|
|
Non-Saudi
|
12 (66.7)
|
6 (33.3)
|
|
Multiple sites
|
Yes
|
9 (100)
|
0 (0)
|
0.06
|
|
No
|
35 (71.4)
|
14 (28.6)
|
|
Readmission
|
Yes
|
7 (77.8)
|
2 (22.2)
|
0.88
|
|
No
|
37 (75.9)
|
12 (24.1)
|
|
Site
|
Mandible
|
18 (94.7)
|
1 (5.3)
|
0.058
|
|
Parotid gland
|
6 (66.7)
|
3 (33.3)
|
|
Palate
|
3 (60)
|
2 (40)
|
|
Skin
|
5 (100)
|
0 (0)
|
|
Others
|
12 (60)
|
8 (40)
|
|
Diagnosis: mean ± SD
|
p
-Value
|
|
Benign lesion
|
Malignant lesion
|
|
Age (y)
|
33.9 ± 17.4
|
55.3 ± 18.5
|
0.001
|
|
Length of stay (d)
|
4.4 ±5.9
|
5.4 ± 2.9
|
0.016
|
|
Time from door-to-diagnosis (d)
|
42.3 ± 67.7
|
29.9 ± 30.8
|
0.610
|
Discussion
This study examined the trends in the prevalence of HNN using the data from a tertiary
care facility for the period 2012 to 2018. Besides, a predictive analysis was conducted
on this dataset to determine the impact of sociodemographic factors and under reporting
of HNN. To the best of our knowledge, this was the first study that assessed the trend
of HNN in Al-Madinah Province and prevalence of HNN has not previously been reported.
Most of the prevalence studies were mainly conducted in the Southern or Eastern provinces
and were either limited to oral cancer[6] or to the study of clinical cases.[15] There is also paucity of data that describe both benign and malignant neoplasms
of the head and neck in descriptive studies in the world literature.[16]
Overall, the results of the present study showed that the majority of diagnosed HNN
cases were benign neoplasms (particularly, pleomorphic adenoma and ossifying fibroma),
while only 14 cases were malignant (mainly, squamous cell carcinoma). These findings
are in line with previous studies conducted in other regions of Saudi Arabia.[8]
[9]
[17] However, this finding is different from that reported in Jazan, Saudi Arabia, where
38% of cases were malignant.[7] The high incidence of malignant cancers in the latter study can be attributed to
the high prevalence of smokeless tobacco use (a well-known risk factor for oral cancer)
in South-western part of Saudi Arabia.[18]
[19] However, the prevalence of cigarette smoking in Al-Madinah was 21.3% among adolescent
males[20] and 9.8% among college-aged females.[21] In Saudi, there has been rapid growth in current electronic cigarette use over the
past few years, particularly among young adults.[22] This rapid increase in tobacco use would have a significant impact on the future
burden of disease in this region. E-cigarettes pose serious health hazards, including
increased risk for heart and respiratory disease but its causal effects on human cancer
would not be known for a few decades. Themes commonly used in antismoking messages
may be effective in educating the public about the potential harm of e-cigarettes.[23]
Additionally, the mandible was the most frequently affected site for benign lesions,
followed by the parotid gland. Intercountry comparisons revealed contradicting results
citing lip and buccal mucosa as common sites for benign lesions.[4] Pleomorphic adenoma was one the most common tumors found among benign neoplasms.[24] Among salivary gland neoplasms similar findings were reported by Tian et al.[25] The etiology of salivary gland tumors is unknown and they comprise 3% of head and
neck tumors in the United States.[26]
A significant difference was found in relation to mean age of patients with the older
people who were more likely to be diagnosed with malignant tumors. This finding consolidates
the findings of previous studies.[18]
[27] Age is a known risk factor for head and neck malignancies.[28] Like many developing nations, Al-Madinah population age-structure is most of younger
cohorts.[10] This composition has a significant impact on the present pattern/type of HNN and
possible future trends. With modernization, this demographic transition is certainly
underway, and the total number of people will increase as will the proportion of older
people. Subsequently, the cancer burden that mainly affect the elderly will also grow.
The mean interval from door-to-diagnosis for malignant lesions was estimated close
to 30 days. This delay is considered unacceptable and efforts should be taken to explore
the reasons for diagnostic delay and to bridge the gaps in getting the diagnostic
service to report any malignancy within 2 weeks. There is a need for primary care
studies on oral cancer diagnosis. The paucity of primary care research in this area
in the global literature was recently highlighted by Grafton-Clarke.[29]
As stated above, this is one of the few studies that documented HNN neoplasms in Saudi
Arabia. This study emphasizes the importance of oral health promotion and disease
prevention programs that is specifically designed to improve oral health literacy
and the quality of life of the population in this region. However, the study has some
limitations worth highlighting. This was a retrospective, hospital-based study and
some essential data were lacking (e.g., different modifiable and nonmodifiable risk
factors that contribute to HNN such as socioeconomic status, tobacco, oral hygiene,
nutritional factors, inherited syndromes, and immunological conditions).[30]
[31] Importantly, the nationality of the patients would be underpinned with further investigation
of ethnicity/origin as this might influence the HNN. This is based on that many Saudi
nationals are of different ethnicity/origin backgrounds. Also, the number of the studied
sample is considered relatively low as only clinically suspected tumors are referred
for histopathological examination. Alternatively, limited awareness or late biopsy
seeking behavior for HNN or the paucity of specialties in the required fields may
be the reason for this low histopathologic reporting. Furthermore, referred patients
may have sought care elsewhere as the maxillofacial pathology service is just recently
established at King Fahad Hospital in Al-Madinah. In addition, the representativeness
of the study findings to whole population of the Al-Madinah is questionable as lifestyle
risk factors and treatment seeking behaviors may differ by the regions. Out of 96
patients, a total of 58 patients had valid biopsy data with preoperative diagnosis.
Therefore, there is a need to biopsy all suspected neoplastic conditions, as recommended
in other Saudi Arabian studies.[7]
Conclusion
When a primary care physician or a dentist is confronted with a head and neck tumor,
the adage “common things happen commonly” should be applied. We report here the frequency
of head and neck tumors found in a pathology service that would be useful for improving
referral services in this region of Saudi Arabia. Diagnostic delays encountered demand
strengthening of guidelines for referral of suspected cancers in the community.
