The study included 2,046 patients in a single medical center and was wide in case number for analysis. However, it overlapped different staging systems (6th, 7th and 8th AJCC editions). We adopted the 7th edition throughout this study. In the study, more than 90% of the participants were male. They were more likely to be diagnosed with oral cancer at a younger age and with late tumor status compared with female patients. This age difference can be explained two folds: first, in betel endemic area, patients develop OSCC at a younger age, compared to other populations not exposed at this risk factor   Second, the female patients were rarely exposed to cigarette, alcohol, and BQ, unlike the male patients, therefore, other factors, as poor oral hygiene, inadequate dental status and chronic irritation, which represents independent risk factors for OSCC, irrespective of tobacco and alcohol consumption, may have played a role in the carcinogenesis . Not smoking, not drinking patients has tend to presents at the extremes of age . It is reasonable that with less carcinogen exposure, female population develop oral cancer later in their lives.
Tongue (55.1%) was the most frequent present anatomical site of oral cancer in female patients; this finding well correlates with the current literature; several studies had reported a higher involvement rate of this subsite, especially in non-smoker non-drinker women with HPV-negative OSCC . On the other hand, we notice a slightly higher median age of our cohort, compared to other study . We interpreted this discrepancy as to the results of the differences in the epidemiological basin assessed. Most of the studies are conducted in western countries, and low OSCC prevalence areas, as a matter of fact, Lin et al  which investigated the clinicopathological features in the Taiwanese population affected by OSCC have obtained similar results regarding the female patients’ age. Furthermore, recent findings, carried by Foy et al. in France have advocated a possible relationship between the development of OSCC in non-smoking, non-drinking patients and viral infection, hypothesizing that changes in western country sexual behaviors may lead to an increased incidence of herpes virus in the oral cavity, especially HSV-2, similarly to what has already been described in HPV-positive oropharyngeal squamous cell carcinoma. Because viral genome integration has not been detected in non-smoking and non-drinking OSCC, a “hit and run” viral mechanism involving epigenome deregulation could therefore play a key role at early steps of oral carcinogenesis in this population of patients. In our cohort, males OSCC were more likely to occur in buccal (38.4%) and tongue (35.3%) locations. The buccal mucosa is the most affected site in people with BQ chewing history due to frequent mucosa irritation. Since most of the male patients (79.9%) had BQ chewing history, buccal cancer was more likely to be found in the male participants. The tumor stage while diagnosed differs between genders. Most (74.3%) of the females had early tumor stage while diagnosed with oral cancer whereas the male patients only had about 60% early tumor stage. However, the lymph node status and the overall stage did not vary between genders. When we did a further analysis in patents with tongue cancer, we found that female patients were diagnosed at an older age and with early tumor size. Besides, in lymph node involvement, the females had fewer ENE if they had lymph node involvement compared to the males (N + ENE+, male: 24.9%; female: 13.3%). In non-smoking and non-drinking OSCC, the frequency of lymph node metastasis and ENE was less frequent than the smoking and drinking group. Although non-significant, the patients that smoked cigarettes and drank alcohol tend to have higher risks of lymph node ENE. It could be related with the mechanisms of tumorigenesis. Those oral cancers related with smoking and BQ could harbour more genetic alterations from the environment carcinogens exposure and can be easier to metastasize or have ENE. The other possibility is the tongue cancers in male are more advanced in stage. The accumulated mutations with tumor stage make tumor cells aggressive in behaviour easier to metastasize.
During the follow-up period, there was no evidence of a difference in recurrence and deaths between genders. Since oral cancer was prevalent in the male population, most of the literature investigated the characteristics, risk factors, treatment, and outcomes of oral cancer in the male population. Few studies investigated this disease in females. We reviewed the studies about oral cancer between genders. Honorato et al. compared the prognostic differences in oral cancer between genders in Brazil. The data showed similar consumption habits of alcohol and cigarette between genders with our population, whereas the anatomical sites of cancer differ from our experiences. It would be due to the lack of using BQ. The tongue was the most affected site in both males and females. Due to the BQ consumption culture in Taiwan, buccal is the most affected site in oral cancer patients in Taiwan, unlike the results showed in Brazil. A study in European countries presented the risk factors of oral and pharyngeal cancer in women in Italy and Switzerland. The study showed that women shared the same major risk factors such as habits of using cigarette and alcohol as men.
The rate of HPV infection in oral cavity cancer was about 13.4% while the infection rate was 36.7% in oropharyngeal cancer in the United States. The HPV infection rate in OSCC is lower than the oropharyngeal cancer. In female OSCC patients, the frequency of HPV infection (9.6%) was much lower than the male (15.8%). In the large cohort study, female OSCC patients had better OS regardless of HPV status. It is the reason we speculated that the survival rates in our study would not be significantly influenced as the HPV status was not determined in in our analysis.
In our study, there were 2,046 participants included, while only 136 patients were female. However, this is one of the largest study recruited the most number of female OSCC underwent surgery as primary treatment. HPV-related head and neck cancer were noted to be increasing in recent years especially in the younger population and those without exposure to tobacco and alcohol. Recently, with the increasing use of smoking in female population. This study provides an epidemiologic data in female OSCC in an BQ endemic area. Further cohort studies at different time periods is mandatory to compare the trends for female OSCCs.