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Keywords:

  • cancer sites;
  • epidemiology;
  • oral cancer;
  • survival rate;
  • trend

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

J Oral Pathol Med (2010) 39: 299–305

Background:  Oral cancer is one of the few life-threatening oral diseases. The subtypes and different sites of oral cancer has different etiology epidemiology and survival rate. Prevalence of the various anatomical oral sites provided potential baseline for improvement of clinical approach.

Methods:  Incidence and survival rates were derived from the Israel National Cancer Registry and included all registered data between 1970 and 2006. Oral cancer included the lips, tongue, buccal mucosa, gums, vestibulum, floor of the mouth, and palate.

Results:  Most prevalent oral cancer subtype was squamous cell carcinoma (SCC) among men above the age of 55 years. Females had a higher incidence of SCC in lateral border of tongue, gums and buccal mucosa. Lymphoma and sarcoma were the most prevalent under the age of 20. Melanomas and metastatic disease revealed the lowest survival rate, while invasive or infiltrating basal cell carcinoma in the lips had the highest rate. The highest oral survival rate was for the lip, and the lowest was for the tongue and gums.

Conclusions:  Early detection of oral cancer is important for all the medical health team. Decrease in lip carcinoma may be a result of occupational or awareness changes and should be studied. Non-epithelial tumors under the age of 20 should be considered as a differential diagnosis. A basic oral examination should be included in all routine medical examinations, with emphasis on high-risk patients and high-risk oral sites.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

In the post-antibiotic era, oral cancer remains as one of the few life-threatening oral diseases in the western world. Oral cancer, globally, is the sixth most common cancer (1) and is a major problem in regions where tobacco habits, in the form of chewing and/or smoking, with or without alcohol intake, are common. Its distribution and occurrence varies by age, ethnic group, culture and life style, and level of country development (2–10).

The most common malignant disease in the oral cavity is squamous cell carcinoma (SCC) (11), but other cancer types diagnosed and included in the present review are non-squamous cell carcinomas, sarcomas, lymphomas, and melanomas.

As some of these tumors are rare, their epidemiological analysis has not been adequately described. Moreover, most reports of oral cancer have described the entire oral and pharyngeal complex. Therefore, the specific biological and anatomical characteristics of cancer in the oral cavity may not always be clear for the general physician. Collecting data over almost four decades offered a distinctive opportunity to analyze rare and specific sites with a significant numbers of cases.

The collection of local epidemiological data on oral cancer in Israel has been sparse and only two publications, with limited data, were located (12, 13). This study is the first to present detailed data collected over four decades.

The aim of this study was to analyze the distribution and trends of oral cancer from 1970 to 2006 among the Israeli population. As a detailed comparative analysis of a large number of cases with a long follow-up, we could characterize the trends in incidence and survival of various oral cancer types, and to correlate these with age, gender, and ethnic origin. The intent was to analyze cancer of the oral region, which includes invasive, infiltrating tumors, and metastases. The association with anatomical oral sites is important for early diagnosis and can serve as a baseline for improvement of clinical approach.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

New cases of cancer are recorded at the Israel National Cancer Registry. The registry collects data among all Israeli citizens. Established in 1960, all relevant medical information concerning malignant cancers among Israeli citizens is delivered to the Registry, on a mandatory basis. The Registry is population-based and includes all new diagnoses and cancer related death rates. Utilization of the human subject data in this study followed the approved protocol and requirements of our Institutional Review Board.

This study included the period between 1970 and 2006. Oral cancer incidence distributions are presented by available registered data: gender, age, ethnicity, histological diagnosis, site of cancer, and 5-year survival rate. Stage of cancer, at diagnosis, was not available from the Registry.

Variables were categorized as follows: age: below 20 years, 20–44 years, 45–54 years, 55–64 years, above 65 years; gender: male, female; ethnicity: Jewish, Arab; sites of cancer were according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (14):

  • • 
    ICD.C00 – lip.
  • • 
    ICD.C02 – tongue.
  • • 
    ICD.C03 – gum.
  • • 
    ICD.C04 – floor of mouth
  • • 
    ICD.C05 – palate.
  • • 
    ICD.C06 – oral mucosa.

Histological subtypes included: Malignant tumor/tumor cells, carcinoma, SCC, verocous carcinoma, large cell squamous cell carcinoma (keratinized/non-keratinized), baso-squamous carcinoma, adeno carcinoma, adenoma, adeno-cystic carcinoma, muco-epidermoid, infiltrating duct carcinoma, acinar carcinoma, adeno-lymphoma, melanoma, sarcoma, pleomorphic adenoma, lymphoma [histological diagnosis codes – 8000/0–9930/3 (14)]. Although basal cell carcinoma (BCC) is a skin originating tumor, it has been included within the analysis of lip cancer in this study, similarly to several other studies (15, 16).

Analyses of associations between variables were conducted employing Log-Rank test for survival and chi-square for categorical variables. Kaplan–Meier 5-year survival plots were calculated. For trend analyses, we included a trend line together with the regression scatter. The R2 value was calculated to demonstrate the fraction of the variance in the data that is explained by the regression model. Level of statistical significance was chosen at P < 0.05. The statistical processing was conducted, employing SPSS 15.0 (SPSS Inc., Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

General description

The total number of new cases diagnosed as oral cancer between 1970 and 2006 was 6577. The average age-standardized rates (ASR) of oral cancer incidence per 100 000 in Israel during these years was 7.34 among Jewish males, 4.26 among Jewish females, 4.87 among Arab males, and 2.15 among Arab females.

Table 1 presents the distribution by histology features. Most cases were SCC (61.1%). Oral melanoma was the least common malignancy. Demographically, most cases were Jewish (94.4%) and males (57.2%). The majority were diagnosed among people aged 55 years or older (73.3%). Males had higher percentages of SCC than females (71.4% vs. 47.2%, respectively). The youngest group had higher percentages of sarcoma and lymphoma (31.0% and 15.5%, respectively), and Arabs had higher percentages of SCC than Jews (74.8% vs. 60.3%, respectively).

Table 1.   Distribution of oral cancer cases in Israel, 1970–2006, by gender, age, ethnicity, and histological diagnosis [% (N)]*
 Total % (N)Squamous cell carcinomaBasal cell carcinomaLymphomaSarcomaMelanomaMetastasisOthers
  1. *Statistical significance cannot be calculated due to small numbers within some categories.

Gender
 Male57.2 (3764)71.4 (2688)17.5 (660)3.6 (137)1.1 (42)0.6 (22)3.8 (142)1.9 (73)
 Female42.8 (2813)47.2 (1329)38.7 (1090)5.5 (154)1.1 (30)0.4 (12)4.1 (114)3.0 (84)
Age
 <201.1 (71)19.7 (14)2.8 (2)15.5 (11)31.0 (22)0 (0)15.5 (11)15.5 (11)
 20–4412.6 (830)62.3 (517)23.1 (192)3.7 (31)1.4 (12)0.8 (7)3.5 (29)5.1 (42)
 45–5413.0 (855)60.0 (513)29.7 (254)4.7 (40)0.7 (6)0.5 (4)2.3 (20)2.1 (18)
 55–6419.3 (1271)60.1 (764)27.3 (347)5.0 (63)1.0 (13)0.7 (9)2.4 (31)3.5 (44)
 65+54.0 (3550)62.2 (2209)26.9 (955)4.1 (146)0.5 (19)0.4 (14)4.6 (165)3.5 (42)
Ethnicity
 Jews94.4 (6208)60.3 (3741)27.6 (1715)4.3 (270)1.0 (65)0.5 (32)3.8 (239)2.4 (146)
 Arabs5.6 (369)74.8 (276)9.5 (35)5.7 (21)1.9 (7)0.5 (2)4.6 (17)3.0 (11)
 Total100 (6577)61.1 (4017)26.6 (1750)4.4 (291)1.1 (72)0.5 (34)3.9 (256)2.4 (157)

Figure 1 illustrates trends by histological subtype of oral cancer from 1970 to 2006. SCC and BCC increased until the 90s and then declined (R2 = 0.74 and 0.64, respectively), while lymphoma cases were stable.

image

Figure 1.  Trends in incidence rates of oral cancer cases in Israel 1970–2006, by histological subtypes.

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Although SCC is the most common malignancy in the oral cavity, some sites demonstrated a high level of tumors of non-epithelial origin. Figure 2 demonstrates the most common malignancies for each mouth location. In all lip sites, the most prevalent tumors were SCC, besides infiltrating BCC in the external upper lip. At the palate (hard and soft), floor of the mouth, and retromolar area, the second most prevalent tumors (more than 25%) were of salivary gland origin.

image

Figure 2.  Distribution of oral cancer in Israel, 1970–2006, by sites, histological nature, and gender (% males/% females).

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Comparison of males to females showed a general trend of higher levels of SCC for each site among males compared with females, besides the cheek mucosa, gums, and border of the tongue.

Survival rates

Survival rates by histological subtype analysis demonstrated a total 5-year survival rate of 67.7%, and excluding metastasis and infiltrating BCC rate of 66.8%.

The lowest 5-year survival rate was for metastasis to the oral cavity and melanoma (46.6% and 47.1%, respectively), while the highest was for infiltrating BCC (81.4%). By site, the lowest 5-year survival rate was for base of tongue with 42.6%, while the highest was for inner aspect of lip with 81.5%.

Figure 3a illustrates survival plots by histological subtypes. Infiltrating BCC demonstrated a higher cumulative survival rate than other histological subtypes’ diagnoses (P < 0.001).

image

Figure 3.  Oral cancer 5-year survival rates in Israel, 1970–2006, by subtype and site.

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Figure 3b illustrates survival plots by anatomical sites. Lip cancer demonstrated more than twice the cumulative survival rate than other anatomical sites (P < 0.001). Figure 3c represents 5-year survival rates by anatomical site. The highest rates were revealed for the external upper lip and the inner aspect of lips. No significant differences were found in the 5-year survival rates by anatomical location (inner/outer/upper/lower) of lip cancer. The lowest survival rate was for the gums: 44.9%.

The most common oral cancer site was the lip with 66.9% of all cases. The total number of lip cancer cases diagnosed between 1970 and 2006 was 4356. Trends in lip cancer incidence from 1970 to 2006 are presented in Fig. 4. The incidence rate of external upper and lower lip cancer had increased till 1999, and then decreased till 2006 (R2 = 0.66 and 0.93, respectively).

image

Figure 4.  Trend in incidence of lip cancer cases in Israel, 1970–2006, by sites.

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The second most common site was the tongue (16.9%), with a total number of 1112 cases diagnosed between 1970 and 2006. Differences by gender, age, and ethnicity were not statistically significant. Trends in tongue cancer incidence from 1970 to 2006 cannot be analyzed due to low R2 values (0.02–0.26). Most cases of tongue malignancies were SCC (62.1%, Fig. 2). No significant differences in the survival plots were detected by anatomical location of tongue cancer. The other common sites in the oral cavity were: gums (6.0%), palate (5.3%), and floor of mouth (3.4%).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

Oral cancer presents a challenging disease for the medical health team. In this study 6577 cases were registered in Israel between 1970 and 2006. The population of Israel in 1970 was estimated to be about 3 022 000 people, and doubled to about 7 200 000 in 2006 (17, 18).

Among all cases, 57.2% were male and 42.8% were female. The global literature generally demonstrates about twice the level of oral cancer among males compared with females (19, 20).

The present available data base did not include lifestyle risk factors. However, comparisons within the Israeli population have demonstrated higher levels of smoking and alcohol consumption among males (21–23). The lifetime risk of alcohol abuse in Israel is similar to European countries (24). A slight decreasing trend has been indicated during 1989–2005 (25). The rate of smoking has decreased from 1980 to 2007 (45% to 26.6% among Jewish males, and 30% to 19.7% among Jewish females) while tobacco and betel nut chewing is very uncommon (26). Sun exposure as a risk factor for lip carcinoma might be an occupational hazard, especially among men.

Most diagnosed patients in this study (73.3%) were above 55 years of age, which is in accordance with the literature (27) and indicates that this age should be included as a risk marker. Most new cases (94.4%) were among the Jewish community. The Israeli population’s Jewish:Arab ratio was about 76%:24% in 2005 (23). Explanations may include higher utilization of health care and lighter skin tone among the Jewish population which in combination with sun exposure is a risk factor for lip cancer. Other factors might and should be considered.

Malignancy type and distribution

The most prevalent oral malignancy was SCC, similar to that described in the literature (28–30). The high percentage of infiltration BCC which was mainly on the upper lip may to be due to the combination of sun exposure among a relatively fair skinned population.

Lymphoma was found to be the third most common malignancy, which is in accordance with the literature (31). The clinician should remember to consider this disease during differential diagnosis of oral lesions. Metastases to the oral cavity were more prevalent than melanoma and sarcoma. Melanoma was found to be very rare. Higher levels of lymphoma and sarcoma at the <20 years age group were similar to the literature (32, 33) and should be remembered by the medical health team when detecting oral cavity lesions.

Both SCC and infiltrating BCC revealed a trend of increasing rates followed by a decrease over recent years (corresponding to doubling of the population size), which can be explained by the same trend in lip cancers. Other cancer types showed similar incidence levels over the years. The low rate of estimated cumulative incidence of alcohol consumption and decreasing rate of smoking may have influenced some of the results regarding SCC (24). However, as it will be further discussed, other possible etiological factors should be considered.

Malignancy type and 5-year survival

The 5-year survival rate for all tumors was 67.7%, similar to that reported in a recent USA study (27, 34) The highest cumulative 5-year survival rate was for Basal Cell Carcinoma, which has been documented to present a relatively good prognosis (35). The survival of SCC patients is higher in this study compared with the USA. This may be due to this study including lip SCC (excluded in the US data), which usually has a good prognosis, with a 45–72% 5-year survival rate (36, 37). Of all oral tumors, melanoma presents the worst survival. Therefore, despite its rarity, it should always be considered by the clinician when diagnosing pigmented lesions. The low survival of patients with metastasis tumors is usually related to the advanced clinical stage of the primary tumors.

Tumor type and oral location

In most oral locations, the most prevalent tumor type was SCC, as is common in the literature. The upper lip was the only location at which the most prevalent type was infiltrating BCC, a skin originating tumor. Among females, the BCC:SCC ratio was higher than among males. This might be correlated to smoking (related to SCC), which is more common among males.

The second most prevalent oral cancer type is of salivary gland origin. Minor salivary glands are anatomically abundant in the oral cavity, and therefore these tumors should be considered in the differential diagnosis of lesions especially at the retromolar area, the palate, and the floor of the mouth.

Innovative methods for early detection of oral tumors have recently been introduced (38). Despite the promising practical results, clinicians should be aware that most of these systems only detect epithelial pathologies. As we have reported in this study, the second most prevalent tumor types are of salivary gland (sub-epithelial) origin. This should especially be noted among younger patients who exhibit a higher prevalence of sub-epithelial tumors.

Males were found to have higher levels of SCC compared to females (excluding buccal mucosa, gums and border of the tongue), and these findings might be associated with higher rates of smoking and drinking among males in Israel. In the buccal mucosa, gums and border of the tongue, higher levels of SCC subtype were found in women. One possible explanation is that these areas are more involved in Oral Lichen Planus, which is over twice more common among women (39) and considered as a possible risk factor with potential eventual malignant transformation (40).

Lip cancer is the most prevalent tumor of all oral tumors among the Israeli population. The distribution of infiltrating BCC of the upper lip and SCC of the lower lip is in accordance with the literature (41). The lower lip is subjected to intense sun exposure and is the most common site of origin for SCC (42) mainly among males in countries characterized by fair skinned people with high sun exposure (43–47). The potential protective value of women’s lipstick should be considered (46). BCC is the most common skin cancer (most common of all cancers), with 85% of tumors of the head and neck (48). Lesions of the upper lip should therefore include infiltrating BCC in the clinical differential diagnosis of a lip tumor. Upper and lower lips showed similarly high survival rates, and this is probably due to the fact that they are both easy to detect and to treat (49–54).

We detected an increasing trend of lip cancer rates followed by a decrease over recent years. A national campaign of skin cancer prevention has been conducted over the last 15 years and may have increased the awareness of both the public and health care providers, resulting in earlier detection and behavioral changes of the public. A decrease in the level of Israelis working outdoors, and thereby lower occupational risk factors related to sun exposure, may also have contributed to this change.

Tongue cancer cases were mainly SCC, as expected. Most of the tongue cancer cases were not specified (66.3%). These findings did not allow representing differences between independent variables such as age, gender or ethnicity.

Summary

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

In this study, we analyzed data of oral malignancies as recorded over a period of 36 years. We found that the most prevalent cancer is SCC with most cases in men and above the age of 55. Higher levels of SCC in the lateral tongue, gums, and buccal mucosa were found among females which may indicate other risk factors than life style and should be further investigated.

Lymphoma and sarcoma were the most prevalent cancers under the age of 20. The second most prevalent cancer in the palate, floor of mouth, and retromolar area was of the salivary gland origin.

The worst survival rates were for melanomas and metastases to the oral cavity, while the highest rate was for infiltrating BCC. Among all oral sites, the best survival rate was for the upper and inner lower lip, and the worst was for the gums. A decreasing trend over time was found in the lips although the population had doubled. The tongue showed different survival rates related to origin and mild differences related to location within the tongue.

The clinician should very carefully examine high-risk patients (over the age of 50, light-skinned people exposed to the sun) and high-risk oral sites (lateral sides of the tongue). When detecting suspicious lesions, healthcare providers should note that non-epithelial malignancies may be involved and should use the appropriate detection methods. Decrease in cancer incidence can be achieved and oral cancer awareness among the public and health care providers can be increased.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

We thank Dr. M. Barchana from The Israeli National Cancer Registration for providing data from the cancer registries.

Conflict of interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References

The authors declare that they have no conflict of interests.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Summary
  8. Acknowledgements
  9. Conflict of interest
  10. References