Survival analysis of age-related oral squamous cell carcinoma: a population study based on SEER

Oral squamous cell carcinoma (OSCC) is the most common histological type of oral cancer, with high morbidity and mortality, accounting for about 90% of oral cancer [1]. Important causes of oral squamous cell carcinoma include smoking, drinking and betel nut chewing [2, 3]. It is worth mentioning that in recent years, human papillomavirus has also been found to be one of the important causes of OSCC [4, 5], which has attracted widespread attention. In the early stages, OSCC are commonly asymptomatic, it is often at advanced-stage at the time of diagnosis. Early detection of precancerous lesions in OSCC can greatly improve the survival rate of patients [6]. In addition, the low survival rate of OSCC is also related to the fact that older patients have more complication, which make them more likely to be infected with other diseases and prematurely die. In addition, there are more adverse drug reactions due to aging organ functions than younger patients. Hence, it has been suggested that different treatment strategies should be given to the young and the old [7]. In this paper, we made a survival analysis based on information of patients with oral squamous cell carcinoma in different ages.

The acquisition of the real data of large number of patients has been one of the main problems faced by researchers in the research process. We used The Surveillance, Epidemiology, and End Results (SEER) national cancer database, a cancer registry maintained by the American College of surgeons and the American Cancer Society. It records the incidence rate, mortality and morbidity of millions of malignant tumors in some states and counties in the United States. The tumor information in the database was unified and standardized by SEER*stat software, and is regularly updated and released. Researchers all over the world can easily get data through application, which provides a good data source for clinical researchers. In addition, SEER database has a large sample size cover about 34.6% of the U.S. population and strong statistical efficiency, which promoted the high clinical reference value of researches based on SEER database.

Age has always been an important factor in the occurrence, development and prognosis of various tumor. Squamous cell carcinoma of the head and neck (HNSCC) is generally considered to be more frequent in the elderly, associated with tobacco and alcohol, and mainly occurs in men [8]. However, more and more young patients with HNSCC have been reported all over the world [9]. For the past few years, the incidence of OSCC has been on the rise, especially among young patients [10].The purpose of this SEER database analysis was to assess the clinical characteristics and risk factors of OSCC in different age groups. At the same time, understanding of other factors (gender, tumor size, histological grade, treatment, etc.) that affect the premature death of patients will help to formulate the corresponding treatment plan in advance and improve the survival rate. To our knowledge, this study is the first to observe the possible differences stratified by age in studies with a large sample size.

As we expected, whether it is OS or CSS, the research shows that the survival time of patients decreases orderly and stepwise with the increase of age group. This result is consistent with other large cohort studies that have been published. A study carried out in Brazil shown that age has a strong impact on mortality from oral and oropharyngeal cancer. The risk increases from 40 years for men to 55 years for women and the effect of the overall period was observed [11]. Laith et al. reported that their study indicated improved OS and disease-specific survival in young patients with oral tongue squamous cell carcinoma (OTSCC) [12]. However, another interesting finding of the regression analysis is that compared with the higher age group, people aged < 30 showed a higher probability of transition, which is not statistically significant [13]. Younger age at diagnosis even was found to be a risk factor for the development of pleural metastasis [14]. In general, the effect of age on the prognosis of OSCC is still controversial. Although a number of studies have made different results, they are unable to explain the etiology and pathological mechanism in detail. From our analysis of the results, young patients (18–39) had a higher rate of surgery (34.11%) and triple therapy (32.05%), indicating that they tend to accept more aggressive treatments.

It has reported that 5-year survival rates for patients with oral squamous cell carcinoma vary greatly by stage, from about 90% in the early stage to about 30% in the late stage [15]. Surgery is the main treatment for early (Stages I–II) oral squamous cell carcinoma. Advanced (Stages III–IV) disease indicates difficulty in obtaining a clear incision margin, which means a higher recurrence rate. Under the circumstance, adjuvant therapy is appropriate [16]. Our research found that age has different effects on prognosis at different stages. In the early stage, the patient's survival period decreased with increasing age. As the stage progresses, the impact of different age groups on the prognosis is less obvious, which is mainly reflected in the poor prognosis of the elderly. Therefore, clinical staging at diagnosis is important and can be used as a predictor of recurrence and death in patients with OSCC.

Based on the results of previous studies, the most common major sites involved in OSCC vary by geographic location. The buccal mucosa is more common in Asian populations, including South Asia, Sri Lanka, etc., where 40% of oral cancers are found in the buccal mucosa due to the common practice of men and women chewing betel nut/tobacco. In contrast, the tongue is the most common site of oral cancer in European and American populations, accounting for 40–50% of oral cancers [17, 18]. The main source of cases in our study is mostly white Americans and our results for the location of OSCC are also within this range. It is worth noting that the proportion of tongue cancer patients is the highest in the 18–39-year-old group (69.29%). This is consistent with a previous study based on a global database analysis [19]. However, the incidence factors of young people are still unclear, and may be related to changes in the etiology of oral cancer, such as human papilloma virus (HPV) infection. In addition, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) analyzed data from the 2011–2015 National Youth Tobacco Survey (NYTS) and determined that the use of e-cigarettes and hooks by middle school students has increased significantly, and the trend is much larger than that of adults [20]. However, it is still necessary to further investigate the influence of young people’s eating habits, lifestyle and other factors on their incidence and tumor location.

As a retrospective study, we acknowledge that there are certain limitations to the study. As for SEER database, a large population retrospective database, inevitably, it has some drawbacks. It does not provide the data of detailed immunohistochemical analysis, for example. It also lacks related chemotherapy or radiotherapy regimens. However, the strengths of our study include a large nationally representative sample, meticulous grouping of age, as well as a wealth of other relevant factors.

Our study revealed that age was an independent predictor of both OS and CSS in the oral squamous cell carcinoma patients, and more aggressive treatments (surgery, triple therapy) tend to be used in young patients, which can provide certain reference value for the current clinical diagnosis and treatment.