INTRODUCTION {#sec1-1}
============

Oral squamous cell carcinoma (OSCC) comprises more than 90% of all oral cavity malignancies. OSCC is a debilitating disease with a 5-year survival rate lower than 50%. It has been shown that the geographical differences and environmental factors affect the OSCC prevalence.\[[@ref1]\]

The prevalence of oral cancers in Iran is 20--36.3 per 100 thousand people.\[[@ref2]\] In Iran, the pattern of epidemiological characteristic of OSCC, is similar to the other cancers.\[[@ref3]\] The studies from 1962 to 2009 in academic centers and hospitals have been shown that the prevalence of OSCC in major cities of Tehran, Mashhad, and Shiraz was 1.29--1.6,\[[@ref4][@ref5][@ref6]\] 0.9--3.1,\[[@ref7][@ref8][@ref9]\] and 1.4%--5%,\[[@ref10][@ref11]\] respectively. The incidence of OSCC in Iran is similar to India and Pakistan.\[[@ref2]\] In recent years, the increasing prevalence of oral cancer has been documented in Asia, especially in India.\[[@ref12]\] Data on OSCC trend in Iran are very limited and insufficient. Updating the data about the epidemiological characteristics of OSCC has not been conducted in Iran in recent years. Despite the available data on demographic information of OSCC, the evaluation of histopathologic pattern of OSCC has not conducted yet, in Iran. The histopathologic grade of OSCC is one of the most important issues to determine the prognosis. Considering the subject, informed the decision-makers about the histopathologic trend of malignant tumors such as OSCC will help the authorities to prepare more facilities for provide the better, effective services to laboratories and patients. The aim was to investigate the histopathologic pattern of OSCC in Iran by analyzing the patients referred to Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, from 2006-2015.

MATERIALS AND METHODS {#sec1-2}
=====================

The study was a retrospective, institutional review. The statistical society was medical records of patients with histopathologic diagnosis of OSCC from archive of Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran, during 2006-2015. The inclusion criteria were complete registered information of medical records about demographic characteristics and histopathologic features. The exclusion criteria were incisional biopsy samples. All samples with histopathologic diagnosis of squamous cell carcinoma (SCC) were retrieved from archive, and cases with oral cavity involvement were included in the study. The histopathologic records that had met the inclusion criteria were investigated. Demographic characteristics (age and gender) and clinicopathologic features (tumor size, anatomic location, differentiation degree, vascular invasion, perineural involvement, and lymph node involvement) were recorded. The clinical appearance of lesions comprising of the color, texture and shape was not included in the registration. There were a total number of 6200 SCCs from 2006 to 2015. Overall, 587 OSCCs were retrieved. Three hundred and fifty-nine incisional biopsies were excluded because of insufficient data of lymph node involvement and invasion state. The frequency of demographic characteristics and histopathologic features was reported. The SPSS software version 19 for windows (SPSS Inc., IBM Co., Chicago, Illinois, USA) was used.

RESULTS {#sec1-3}
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The age ranged from 15 to 93 years with a mean of 59.3 ± 15.7 years. The seventh and eighth decades (*n* = 136, 23.2% and *n* = 135, 23%, respectively) included the highest incidence of disease. The least number of cases was obtained from tenth and second decades (*n* = 3, 0.5% and *n* = 6, 1%, respectively). Three hundred and fifty (59.6%) OSCCs occurred in males and 236 (40.2%) in females. The male-to-female ratio was 1.48:1. Tongue was the most common site of OSCC with 224 cases (38.2%), followed by mandible (108, 18.4%). Vestibule (5, 0.9%) and gingiva (8, 1.4%) were the least prevalent anatomic sites of OSCC \[[Table 1](#T1){ref-type="table"}\].

###### 

Frequency of clinical features of oral squamous cell carcinoma during 2006-2015 based on the number of cases

  Variable       Years                                           
  -------------- ------- ---- ---- ---- ---- ---- ---- ---- ---- ----
  Age                                                            
   10-20         0       0    2    1    1    0    0    2    0    0
   21-30         0       2    4    2    2    2    2    4    1    1
   31-40         2       1    4    3    3    9    3    10   8    4
   41-50         0       5    3    9    5    20   10   18   5    6
   51-60         2       7    6    7    15   16   22   26   6    8
   61-70         6       8    7    5    13   18   22   32   18   7
   71-80         4       8    9    11   15   18   17   29   12   12
   81-90         1       1    2    1    8    9    5    8    2    3
   91-99         0       0    0    0    0    0    3    0    0    0
  Gender                                                         
   Male          7       20   23   24   33   56   49   82   30   26
   Female        8       12   15   16   29   36   35   48   22   15
  Site                                                           
   Tongue        4       10   19   16   19   34   40   53   16   13
   Mandible      8       7    5    7    12   12   15   27   6    9
   Lip           1       7    6    7    6    27   12   19   15   6
   Buccal        0       0    1    0    12   7    4    14   6    6
   Mouth floor   1       5    2    2    8    3    3    5    3    1
   Maxilla       0       2    2    5    4    3    6    6    2    3
   Palate        0       0    1    0    1    5    3    4    3    3
   Gingiva       1       0    0    2    0    2    1    2    0    0
   Vestibule     0       1    2    1    0    0    0    0    1    0

Two hundred and sixty-eight (45/7%) cases of all samples were well differentiated, followed by moderate (249, 42.4%) and poor differentiation (38, 6.5%). Tumor size ranged from 0.4 to 11 cm with a mean of 3/0 ± 1.77 cm. The lymph node involvement, vascular invasion, and perineural involvement were found in 179 (41.8%) of 428, 153 (33.6%) of 456, and 193 (42.9%) of 450 cases, respectively \[[Table 2](#T2){ref-type="table"}\].

###### 

Frequency of histopathologic finding of oral squamous cell carcinoma during 2006-2015 based on the number of cases

  Variable              Years                                           
  --------------------- ------- ---- ---- ---- ---- ---- ---- ---- ---- ----
  Grade                                                                 
   Well                 10      13   17   21   34   45   34   55   19   20
   Moderate             5       15   16   11   23   42   42   57   27   14
   Poor                 0       0    0    2    2    4    5    12   8    5
  Size                                                                  
   0-2                  3       4    7    15   12   21   27   33   12   9
   2.1-4                8       12   9    15   21   44   29   54   21   16
   4.1-6                0       7    17   4    11   18   21   31   10   10
   6\<                  1       1    0    2    3    10   6    12   9    4
  Vascular invasion                                                     
   +                    3       4    10   7    12   18   27   31   23   18
   -                    5       13   14   13   22   61   50   84   23   18
  Perineural invasion                                                   
   +                    1       6    14   12   13   35   27   46   21   18
   -                    3       8    7    11   23   46   49   73   21   16
  Lymphatic invasion                                                    
   +                    7       16   14   7    15   28   23   42   15   12
   -                    6       11   19   25   33   34   33   50   21   17

+: With involvement; -: Without involvement

From 2006 to 2015, the histopathologic grade of OSCC had increasing number toward moderate and poor differentiation. In coordinate to histopathologic differentiation, tumor size and invasion to vascular and perineural structures had higher prevalence. In the period of the study, lymph node involvement had an irregular pattern until 2011. Contrary, the pattern of lymph node involvement followed a linear model \[[Figure 1](#F1){ref-type="fig"}\]. Despite the higher number of well-differentiated OSCC as a whole, a higher incidence of moderately and poorly differentiated cases was indicated during 2010--2014 and 2012--2015, respectively.

![The trend of histopathologic parameters of oral squamous cell carcinoma during 2006--2015](JRMS-24-53-g001){#F1}

DISCUSSION {#sec1-4}
==========

The oral cancer comprises almost 2% of all cancers in the United States,\[[@ref1]\] and it is the most frequent one in India.\[[@ref13]\] In Asia, the occurrence of OSCC in Pakistan and Sri Lanka had increasing and decreasing trends in recent years, respectively.\[[@ref12]\] The pattern of OSCC incidence in Iran is similar to India and Pakistan.\[[@ref2]\] Data on OSCC trend in Iran are very limited. Basically, studies have been focused on the demographic changes of OSCC. The available information on histopathologic changes of OSCC is very small and insufficient. The histopathologic pattern of OSCC in Iran was investigated retrospectively by analyzing the pathologic records of OSCC in Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran, during 2006-2015.

The results showed that from the total cases of OSCC during 2006--2015, 45/7%, 42.4%, and 6.5% of cases were well, moderately, and poorly differentiated, respectively.

The finding is compatible with previous studies. The studies showed the most prevalence of well-differentiated OSCC.\[[@ref14][@ref15][@ref16][@ref17]\] The findings were different from some previous reports which showed a more prevalence rate of moderately- and poorly differentiated OSCCs.\[[@ref18][@ref19]\] The difference can be due to the type of samples. Unlike surgical specimens, diagnostic specimens in patients referred to clinics or patients who are involved with unknown lesions are typically in the form of incisional. Because of this, it does not represent all aspects of tumor such as lymph node involvement. In contrast, hospital-derived specimens consist of lesions as a whole and include all parts of the tumor. In these circumstances, pathologist has more insight to overcome the pitfalls of histopathologic diagnosis.

Despite the higher number of well-differentiated OSCC as a whole, the peak incidence of moderately and poorly differentiated cases was during 2010--2014 and 2012--2015, respectively. The finding is in agreement with Sherin *et al*. in India who showed more prevalence of moderately differentiated OSCC in both young adult and older age groups.\[[@ref20]\]

Using Broder\'s criteria in histopathologic grading, Ur Rahaman and Ahmed Mujib reported no difference in OSCC between younger and older (40 years old age) patients. Using Anneroth *et al*. classification, results showed higher grades of histopathologic parameters in youngers.\[[@ref21]\] The finding indicated the aggressiveness of OSCC in younger patients. In the present study, data were not restricted to any age group. Compatible with previous studies, higher histopathologic grades in population were noted.

The progression of the tumor that represents an invasion of a tumor is not only determined by an increase in the size but also characterized by an increase in the heterogeneity of the tumor and an increase in malignancy. Heterogeneity results from multiple and independent mutations in tumor cells. This causes the invasion, the rate of growth, and even the response to treatment. Monoclonal cells become heterogenic over time and affect the clinical course of the tumor. Immunologic factors can also change this process. Chemical and environmental factors and viruses can cause cancer-induced genetic damage and affect the malignancy.\[[@ref22]\] Cancer progresses take years to develop. The effect of various carcinogenic factors during this period can affect the course of the disease. The study findings showed that in addition to increasing the histopathologic grade, the size of the tumor and its invasion also increased. More biologic and molecular studies need to investigate the causes of malignant up trend of OSCC.

Social and cultural variables have important impact on oral cancer. Human papillomavirus infection and tobacco and alcohol consumption are among the most important factors in developing the OSCC. It has been shown that in United States, the females in younger ages were more prone to oral cavity cancers as in mid 1990s.\[[@ref23]\]

The epidemiologic studies revealed that a pattern of OSCC features in Iran is similar to other countries. Based on results, in Iran, OSCC is more prevalent in males, tongue and older adults. The well-differentiated OSCC comprises the most cases.\[[@ref3]\]

Despite the available information on the epidemiological situation of OSCC in Iran, the possible changing trend has not been studied. Since the registration of disease outbreaks is essential for health planning, determining the possible changes in the course of the disease is an important issue.

The present study was single centered. Therefore, it cannot reflect the whole condition of the Iranian society. In spite of this limitation, due to the fact that the Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran contained the samples of patients from different provinces, it can reflect the present status. Expressing the general condition of Iran, multicentral studies are necessary. In the present study, the sex and age status of patients on the histopathological profile of cancer were not investigated. The impact of age and sex on the extent of malignancy is suggested in future studies.

CONCLUSION {#sec1-5}
==========

On the basis of histopathologic features, moderately differentiated OSCC with increasing rate of tumor size and vascular, perineural invasion was indicated in recent decade. The recent prevalence of higher histopathology grades of OSCC can contribute to modern lifestyle and environmental factors. Determining the present inclination in histopathologic grade of OSCC requires community health research.

Financial support and sponsorship {#sec2-1}
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Biological materials were provided by the Iran National Tumor Bank which is funded by Cancer Institute of Tehran University of Medical Sciences, for Cancer Research.

Conflicts of interest {#sec2-2}
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There are no conflicts of interest.

The authors thank the staff of Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, for kindly assistance in archive retrieval. The study was approved by the Ethical Committee of Shahed University under registration number IR.Shahed.REC. 1396.55.
