Oral Cancer Staging and Clinicopathologic Features Presenting to Oral & Maxillofacial Surgery Practice in Saudi Arabia
Basem T. Jamal1,2*
1Consultant and Associate Professor Oral & Maxillofacial Surgery/Head and Neck Surgical Oncology, King AbdulAziz University, Jeddah, Saudi Arabia. 2Affiliate Consultant, Oral & Maxillofacial Surgery Department, King Abdullah Medical City, Makkah, Saudi Arabia.
The most common type of head and neck cancer, oral cancer (OC), is the 16th most common malignancy and the 15th most frequent cause of cancer-related deaths in the world. There has been an increase in the incidence of OC in Saudi Arabia in recent years. The survival rate of oral cancer is one of the lowest in the world and still, unfortunately, a large number of OC cases are discovered in advanced stages. The purpose of this study is to assess the prevalence of advanced stages of oral cancer in maxillofacial surgical oncology practice in Saudi Arabia. Patients diagnosed with oral cancer presented to the oral and maxillofacial surgery clinic at 2 institutions where the author's work was identified. Primary data extracted from the database included age, sex, histologic subtype, tumor site, and TNM stage. A total of 156 records of patients with oral cancer confirmed by histopathology were assessed. The mean age of patients was 59.2 years. The majority of the patient presented at an advanced stage, 79% with a distribution as follows: 11% Stage I, 10% Stage II, 16% Stage II, and 63% Stage IV. The positive nodal disease was diagnosed in 58% of the tumors. The study reflects the high prevalence of advanced oral cancer cases in Saudi Arabia as experienced by an oral and maxillofacial surgery practice and it highlights the need for more collaboration between the centers to ensure timely diagnosis and referral of oral cancer patients.
Keywords: Oral cancer, Advanced cases, Saudi Arabia, Maxillofacial surgery
The most common type of head and neck cancer, oral cancer (OC), is the 16th most common malignancy and the 15th most frequent cause of cancer-related deaths in the world. The geographical incidence of this cancer is, however, extremely variable, and several factors are involved, including cultural habits, availability of health services, and economic circumstances. It is estimated that there were 377,713 new cases of lip and oral cancer worldwide in 2020 and that there were 177,757 deaths due to this disease. Globally, over 450,000 patients are diagnosed with OC each year, and the five-year survival rate is below 50%.[4, 5]
In Arab Gulf countries, oral cancer is relatively uncommon; however, Saudi Arabia is an exception to this rule. There has been an increase in the incidence of OC in Saudi Arabia in recent years. The Tumor Registry of King Faisal Specialist Hospital & Research Center in Riyadh indicates that OC accounts for 4% of all cancers in Saudi Arabia. They found that OC was the fifth most common cancer among males and the eleventh most common cancer among females. Oral cancer is more prevalent in Saudi Arabia than in surrounding Gulf countries, such as Kuwait and the United Arab Emirates, which share similar geographical and cultural characteristics. Approximately 26 percent of all head and neck cancers detected annually in KSA are oral cancers, most of which are in advanced stages requiring palliative care. Several studies have shown that the use of Shamma, a form of smokeless tobacco, is associated with the high incidence of oral cancer mentioned earlier.[7, 9]
The survival rate of oral cancer is one of the lowest in the world. Despite the ease with which malignant lesions may be detected in the oral cavity, it is unfortunate that a significant number of oral cancer cases are discovered at an advanced stage. According to a meta-analysis, diagnosis delay was likely to be a contributing factor to advanced-stage OC and mortality.[7, 10]
The survival rate for oral squamous cell carcinoma has only marginally improved despite advancements in imaging
techniques (including computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasound), surgical techniques, radiation therapy sources and delivery methods, and combination with chemotherapy.[11, 12] Many patients who have had successful treatment for oral cancer may experience functional and cosmetic impairments, including difficulties eating, swallowing, speaking, and disfigurement which may have a significant adverse impact on their quality of life. Early detection of oral cancer is the most effective way to reduce morbidity and disfigurement as well as improve survival rates. Worldwide statistics on oral cancer staging prevalence show that 55-75% of oral cancer patients are diagnosed at advanced stages (stages III–IV), with corresponding 5-year overall survival ranging from 33-63%.[1, 11, 15-26] A systematic review of oral cancer in Saudi Arabia found that all patients enrolled in the study visited the hospital at an advanced stage, and the 5-year survival rate varied from 12.9% to 24.4%.
In general, early detection of oral cancer improves survival rates to more than 80%, compared to less than 20% for advanced diseases worldwide. The purpose of this study is to assess the prevalence of advanced stages of oral cancer in maxillofacial surgical oncology practice in Saudi Arabia.
Materials and Methods
Patients diagnosed with oral cancer presented to the oral and maxillofacial surgery clinic at 2 institutions where the author's work was identified. The institutions are King Abdulaziz University Hospital and King Abdullah Medical City, Saudi Arabia. Records from 2015-2022 of patients treated at the oral and maxillofacial surgery department were included.
Primary data extracted from the database included age, sex, histologic subtype, tumor site, and TNM stage. The primary focus of this study is to report on the prevalence of advanced-stage oral squamous cell carcinoma in Saudi Arabia as experienced in maxillofacial oncology practice.
Tumors of salivary glands origin, melanomas, sarcomas, as well as verrucous carcinomas were excluded. 156 records of patients with oral cancer confirmed by histopathology were reviewed. Patients were categorized as early (I & II) or advanced (III & IV) stages and staging was assessed using the American Joint Committee on Cancer TNM staging system eighth edition. Age was analyzed as a continuous variable. We obtained information regarding the patient's age, gender, anatomical location, and histopathological diagnosis for every case. Lesions were categorized according to the site as lip, tongue, the floor of the mouth (FOM), cheek (buccal mucosa), mandible, retromolar area, and maxilla (palate).
Results and Discussion
A total of 156 patients had histologically diagnosed squamous cell carcinoma of the oral and maxillofacial area. Of these cases, 55% were men and 45% were women. The mean age of patients was 59.2 years (S.D. = 15.2), (range, 21–93 years). The median age was 60.5.
The percentage distribution of the affected areas was: 40.5% tongue, 25.5% cheek, 17% mandible, 7% maxilla, 4% lower lip, and FOM, and finally 2% retromolar area. The frequency of distribution among the oral anatomical sites is shown in Figure 1.
Figure 1. Frequency of distribution among the oral anatomical sites
The majority of the patient presented at an advanced stage, 79% with a distribution as follows: 11% Stage I, 10% Stage II, 16% Stage II, and 63% Stage IV as shown in Figure 2. The positive nodal disease was diagnosed in 58% of the tumors, the majority of which with extranodal extension (ENE). Figure 3 shows the prevalence of the positive nodal disease.
Figure 2. Oral Cancer staging
Over three-quarters of the study, the cohort had advanced oral cancer, and the majority of them were male. Cancer patients with advanced stages were found to be older than those with early-stage cancers.
Figure 3. Nodal disease among the cohort of patients
Oral cancer remains associated with a poor prognosis despite improvements in diagnosis and treatment; in large part due to a delay in the diagnosis of the disease until it is at a late stage. A study of the national cancer database in the USA between 1998 to 2006 revealed that late-stage disease ranged from 32.5-36% Another study on oral cancer patients in Memorial Sloan Kettering Cancer Center from 1985-2015 of a cohort of over 2000 patients revealed advanced-stage cancer in only 25% and hence the 5-year overall survival of 64.4%. However, that overall survival was not the same across the US with the SEER database indicating 5-year survival ranging from 42.7-52%.
It has been recognized that the stage of the disease at diagnosis is one of the most significant prognostic factors in oral cancer. When oral cancer is detected in an early stage when it is amenable to single modality therapy, there is the best chance of reducing mortality from these diseases in the short term. Unfortunately, two-thirds of patients with oral cancer are still diagnosed at an advanced stage of the disease (stage III and IV) [31, 32] having a 5-year survival rate of 50% or less. As opposed to approximately 80% survival rate in patients with localized disease, which makes the differences in mortality rates based on staging very apparent. In Brazil, Kowalski et al. have demonstrated the potential for clinical upstaging of head and neck cancer before treatment initiation. They also demonstrated that the median 5-year survival rate of patients with clinical upstaging before treatment which was 17.2 months was significantly lower than patients without clinical upstaging and who received treatment within 1-3 weeks and they had a 5-year survival rate of 32.7 months. According to Tsai et al., patients with oral cancer in Taiwan who were treated after 30 days from diagnosis had a lower overall survival rate than those who were treated within 30 days; the trend observed remained unchanged after stratification by the initial stage of the tumor at diagnosis. Van Harten et al. found that longer waiting times for treatment initiation were significantly associated with poorer overall survival in patients with head and neck cancer in the Netherlands.
Our study findings reflect a staggering nearly 80% prevalence of advanced oral cancer cases most of which are in stage 4, 63%. A subset analysis of the patient following the COVID pandemic starting from March 2020 at one of the centers reviewed in the study shows an advanced stages prevalence of 88%. This high incidence of advanced cases is also manifested in the high prevalence of positive nodal disease which occurred in 58% of the cases compared to 29% of the cohort of the patient from Memorial Sloan Kettering Cancer Center. Throughout Saudi Arabia, the prevalence of oral cancer varies by region, with a 30-fold difference in age-standardized rates between the lowest and highest incidences. For instance, Jazan (Gizan) ranked highest in head and neck cancer prevalence in Saudi Arabia; more specifically, oral cancer ranked first among females and second among males. In several studies, the cause of the high incidence of oral cancer in the Jazan region has been investigated.[9, 39, 40] These researchers found that consuming Shamma significantly increased the risk of developing oral cancer by 29-fold.
Many factors contribute to this high incidence of advanced cancer stage at specialized centers. Among the causes is late consultation due to patients dismissing the signs and symptoms as inflammatory and self-resolving. Another factor is the lack of centralization of management with all centers deciding on what cancers to treat and what cancers to refer and that is a negative double edge sword; first, it leads to the majority of cases at specialized centers being advanced and with poor prognosis and secondly it means that simpler cases are treated at non-specialized centers and by non-oncology practitioners who would not treat the cases appropriately reducing their cure rates and ultimately increasing their recurrence which negatively affect the overall outcome of care in the region. Centers that do not have practitioners specializing in oral cancer care or do not have the facility to provide comprehensive treatment to their patients should take a professional stance to refer all oral cancer patients to centers that can provide that.
Several strategies can be used to detect oral cancer at an early stage, including screening high-risk populations, opportunistic screenings by general practitioners, as well as reducing the time between the diagnosis and treatment. It has been shown that fast-track policies for urgent referrals for suspected cancer have been effective in reducing diagnostic intervals in several cancers since they were implemented in 2005 in the UK. Head and neck cancer patients, for example, have experienced a 21-day reduction in diagnostic intervals.
In conclusion, this study reflects the high prevalence of advanced oral cancer cases in Saudi Arabia as experienced by an oral and maxillofacial surgery practice and it highlights the need for more collaboration between the centers to ensure timely diagnosis and referral of oral cancer patients.
1. Ferlay J, Ervik M, Lam F. Global Cancer Observatory: Cancer Today 2020. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac. 21492
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
4. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. doi:10.3322/caac.21262
5. Ren ZH, Xu JL, Li B, Fan TF, Ji T, Zhang CP. Elective versus therapeutic neck dissection in node-negative oral cancer: Evidence from five randomized controlled trials. Oral Oncol. 2015;51(11):976-81. doi:10.1016/j.oraloncology.2015.08.009
6. Al-Jaber A, Al-Nasser L, El-Metwally A. Epidemiology of oral cancer in Arab countries. Saudi Med J. 2016;37(3):249-55.
7. Alotaibi ON. Oral and maxillofacial cancer: A 35-year retrospective analysis at a referral dental hospital in Saudi Arabia. Saudi Dent J. 2022;34(1):56-61.
8. Gupta BM, Gupta R, Ahmed M. Mouth Cancer Research: A Quantitative Analysis of World Publications, 2003-12. DESIDOC J Library Info Technol. 2014;34(3):232-40.
9. Alsanosy RM. Smokeless Tobacco (Shammah) in Saudi Arabia: A review of its pattern of use, prevalence, and potential role in oral cancer. Asian Pac J Cancer Prev. 2014;15(16):6477-83.
10. Seoane J, Alvarez-Novoa P, Gomez I, Takkouche B, Diz P, Warnakulasiruya S, et al. Early oral cancer diagnosis: The Aarhus statement perspective. A systematic review and meta-analysis. Head Neck. 2016;38 Suppl 1:E2182-9. doi:10.1002/hed.24050
11. Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001.
12. Zanoni DK, Montero PH, Migliacci JC, Shah JP, Wong RJ, Ganly I, et al. Survival outcomes after treatment of cancer of the oral cavity (1985–2015). Oral Oncol. 2019;90:115-21.
13. Chandu A, Smith AC, Rogers SN. Health-related quality of life in oral cancer: a review. J Oral Maxillofac Surg. 2006;64(3):495-502.
14. Scott S, McGurk M, Grunfeld E. Patient delay for potentially malignant oral symptoms. Eur J Oral Sci. 2008;116(2):141-7.
15. Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Estimativa 2018 - Incidência de câncer no Brasil. Rio de Janeiro: Inca; 2017. 130p. Available from: http://www.inca.gov.br/estimativa/2018/ estimativa-2018.pdf
16. Chin D, Boyle GM, Porceddu S, Theile DR, Parsons PG, Coman WB. Head and neck cancer: past, present and future. Expert Rev Anticancer Ther. 2006;6(7):1111-8.
17. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709-20.
18. Marur S, Forastiere AA. Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016;91(3):386-96.
19. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-16.
20. Listl S, Jansen L, Stenzinger A, Freier K, Emrich K, Holleczek B, et al. Survival of patients with oral cavity cancer in Germany. PLoS One. 2013;8(1):e53415.
21. Jakobsen KK, Grønhøj C, Jensen DH, Karnov KKS, Agander TK, Specht L, et al. Increasing incidence and survival of head and neck cancers in Denmark: a nationwide study from 1980 to 2014. Acta Oncol. 2018;57(9):1143-51.
22. Brandizzi D, Gandolfo M, Velazco ML, Cabrini RL, Lanfranchi HE. Clinical features and evolution of oral cancer: A study of 274 cases in Buenos Aires, Argentina. Med Oral Patol Oral Cir Bucal. 2008;13(9):E544-8.
23. Momares DB, Contreras CG, Martínez RB, Ávalos JN, Carmona RL. Sobrevida en Carcinoma Espinocelular de Mucosa Oral: Análisis de 161 pacientes. Rev Chil Cir. 2014;66(6):568-76.
24. Schneider IJ, Flores ME, Nickel DA, Martins LG, Traebert J. Survival rates of patients with cancer of the lip, mouth, and pharynx: a cohort study of 10 years. Rev Bras Epidemiol. 2014;17(3):680-91.
25. Monteiro LS, Antunes L, Santos LL, Bento MJ, Warnakulasuriya S. Survival probabilities and trends for lip, oral cavity, and oropharynx cancers in Northern Portugal in the period 2000-2009. Ecancermedicalscience. 2018;12:855.
26. Kowalski LP, Oliveira MM, Lopez RVM, Silva DRME, Ikeda MK, Curado MP. Survival trends of patients with oral and oropharyngeal cancer treated at a cancer center in São Paulo, Brazil. Clinics (Sao Paulo). 2020;75:e1507. doi:10.6061/clinics/2020/e1507
27. Basha S, Mohamed RN, Al-Thomali Y, Al Shamrani AS. The Prevalence of Oral Cancer in Saudi Arabia - A Systematic Review. Ann Med Health Sci Res. 2019;9(2):553-7.
28. Asio J, Kamulegeya A, Banura C. Survival and associated factors among patients with oral squamous cell carcinoma (OSCC) in Mulago hospital, Kampala, Uganda. Cancers Head Neck. 2018;3:9. doi:10.1186/s41199-018-0036-6
29. Schwam ZG, Judson BL. Improved prognosis for patients with oral cavity squamous cell carcinoma: Analysis of the National Cancer Database 1998–2006. Oral Oncol. 2016;52:45-51.
30. SEER Program. SEER* Stat Database: Incidence-SEER 18 Regs Research Data+Hurricane Katrina Impacted Louisiana Cases, Nov 2017 Sub (2000– 2015) < Katrina/Rita Population Adjustment > - Linked to County Attributes - Total U.S., 1969–2016 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2018, based on the November 2017 submission. Available from: www.seer.cancer.gov
31. Jitender S, Sarika G, Varada HR, Omprakash Y, Mohsin K. Screening for oral cancer. J Exp Ther Oncol. 2016;11(4):303-7.
32. Güneri P, Epstein JB. Late stage diagnosis of oral cancer: components and possible solutions. Oral Oncol. 2014;50(12):1131-6.
33. Stefanuto P, Doucet JC, Robertson C. Delays in treatment of oral cancer: a review of the current literature. Oral Surg, Oral Med, Oral Pathol Oral Radiol. 2014;117(4):424-9.
34. Grafton-Clarke C, Chen KW, Wilcock J. Diagnosis and referral delays in primary care for oral squamous cell cancer: a systematic review. Br J Gen Pract. 2019;69(679):e112-e26. doi:10.3399/bjgp18X700205
35. Kowalski LP, Carvalho AL. Influence of time delay and clinical upstaging in the prognosis of head and neck cancer. Oral Oncol. 2001;37(1):94-8. doi:10.1016/s1368-8375(00)00066-x
36. Tsai WC, Kung PT, Wang YH, Huang KH, Liu SA. Influence of time interval from diagnosis to treatment on survival for oral cavity cancer: A nationwide cohort study. PLoS One. 2017;12(4):e0175148. doi:10.1371/journal.pone.0175148
37. Van Harten MC, Hoebers FJP, Kross KW, Van Werkhoven ED, Van Den Brekel MWM, Van Dijk BAC. Determinants of treatment waiting times for head and neck cancer in the Netherlands and their relation to survival. Oral Oncol. 2015;51(3):272-8.
38. Brown A, Ravichandran K, Warnakulasuriya S. The unequal burden related to the risk of oral cancer in the different regions of the Kingdom of Saudi Arabia. Community Dent Health. 2006;23(2):101-6.
39. Quadri MFA, Alharbi F, Bajonaid AMS, Moafa IHY, Al Sharwani A, Alamir AHA. Oral squamous cell carcinoma and associated risk factors in Jazan, Saudi Arabia: a hospital-based case-control study. Asian Pacific J Cancer Prev. 2015;16(10):4335-8.
40. Alshehri BM. Trends in the incidence of oral cancer in Saudi Arabia from 1994 to 2015. World J Surg Oncol. 2020;18(1):1-6.
41. Macpherson LMD. Raising awareness of oral cancer from a public and health professional perspective. Br Dent J. 2018;225(9):809-14.
42. Neal RD, Din NU, Hamilton W, Ukoumunne OC, Carter B, Stapley S, et al. Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database. Br J Cancer. 2014;110(3):584-92. doi:10.1038/bjc.2013.791