Squamous Cell Carcinoma: A Silent Killer

Squamous Cell Carcinoma is a deadly malignancy disease that primarily affects the oral cavity tissue and accounts for more than 90% of all oral malignancies [1]. OSCC dramatically affects patients’ quality of life, resulting in high morbidity and mortality rates. The risk factors of OSCC can include tobacco, alcohol consumption, and human papillomavirus (HPV) infection [1]. Other potential risk factors include chronic dental trauma, microbiome abnormalities, marijuana consumption, and genetic disorders. However, Oral squamous cell carcinoma appears distinct in non-smoking and non-drinking (NSND) individuals and younger ages.[2] The prognosis for such cases is still under research investigation, although some studies suggest they may have a higher risk of relapse and worse 5-year disease-free survival than older patients [3].

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Clinical features

Oral squamous cell carcinoma (OSCC) manifests with different clinical features. Symptoms that should alert clinicians to examine patients for OSCC include chronic pain in the throat, chronic sore tongue, non-healing ulcers or red/white patches in the mouth, persistent hoarseness, painful or difficulty swallowing, and neck masses. The most common sites for OSCC are the tongue (Figure 1) and the floor of the mouth. The SCCs of the oral cavity can manifest as ulcers or masses, with early-stage lesions appearing as flat, discolored areas known as leukoplakia or erythroplakia. As the disease progresses, it may invade surrounding structures, leading to concerning symptoms like tooth mobility, trismus, sensory changes, referred to as otalgia, and the presence of masses in the neck region [4,5].

Figure 1. OSCC of the lateral tongue

Diagnosis of OSCC

Dentists and oral pathologists play an essential role in the early detection and diagnosis of oral squamous cell carcinoma (OSCC). Dentists often are the first to detect oral lesions during the physical examination of the oral cavity and refer to oral pathologists to diagnose OSCC by examining biopsy specimens for histopathological features of malignancy. They may also use advanced diagnostic techniques, such as molecular biology and cytology, to identify malignant or premalignant oral lesions. However, the clinical manifestation of OSCC can resemble other common oral lesions, emphasizing the need for careful differential diagnosis [4,1,8].

The fatality mechanism of OSCC

Oral squamous cell carcinoma can be fatal through various mechanisms. The cancer’s progression, local invasion of nearby organs, and distant metastasis are the primary causes of death. The lesions’ aggressive growth can rapidly invade and damage surrounding structures, such as the airway, leading to airway blockage, bleeding, and severe infections. Distant metastasis, especially to vital organs like the lungs, significantly affects the disease’s survival rates. Patients undergoing resection for OSCC (oral squamous cell carcinoma) are at high risk for cardiovascular and respiratory complications, recognized as significant mortality factors. Additionally, history of tobacco and alcohol usage is common between OSCC patients, which can further complicate their overall health status which contributes to lung and esophageal cancers and circulatory and digestive system diseases, leading to various complicated health challenges. However, the risk of death increases significantly with each additional pack-year of tobacco smoking [6,7].

Treatment Options

Treatment for oral squamous cell carcinoma is multidisciplinary and includes surgery, radiation therapy, and systemic therapy based on the location, the stage, and the patient’s health status. For early-stage OSCC, surgery is often the first-line treatment. Another primary treatment protocol for OSCC is radiation therapy alone or combined with systemic therapy. Therefore, systemic therapies, including chemotherapy and targeted therapy, are typically the choice for advanced or metastatic disease[4,9,10].


Prognostic FactorsImpact on Prognosis
Disease StageEarly-stage have a better prognosis than advanced stage.
AgeYoung adults (≤40 years) have a poorer prognosis compared to older adults.
ComorbiditiesTobacco, alcohol consumption has a worse prognosis.
HPV Status of TumorHPV-positive tumors in oropharyngeal SCC indicate a better prognosis than HPV-negative tumors.
Treatment TypePatients receiving combined surgery and adjuvant therapy exhibit a better prognosis.

The prognosis of OSCC is influenced by multiple aspects, for example: disease stage, age, co-existing conditions, HPV status, and treatment modality.


Variable clinical manifestations of OSCC, including indolent appearances, can delay diagnosis and worsen prognosis. Most cases are diagnosed at late stages resulting in a near 50% five-year survival rate. However, early cancer detection significantly reduces the chances of recurrence and death. Dentists are increasingly involved in the early detection of oral cancers and do not neglect any intraoral lesions. Educating patients about the risk factors for oral cancers and maintaining good oral hygiene.

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  1. Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, Kalia K, Mandoli A. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral Oncol. 2021 Oct;121:105451. doi: 10.1016/j.oraloncology.2021.105451. Epub 2021 Jul 28. PMID: 34329869.
  2. Tran Q, Maddineni S, Arnaud EH, Divi V, Megwalu UC, Topf MC, Sunwoo JB. Oral cavity cancer in young, non-smoking, and non-drinking patients: A contemporary review. Crit Rev Oncol Hematol. 2023 Oct;190:104112. doi: 10.1016/j.critrevonc.2023.104112. Epub 2023 Aug 24. PMID: 37633348; PMCID: PMC10530437.
  3. Yan EZ, Wahle BM, Nakken ER, Chidambaram S, Getz K, Thorstad WL, Zevallos JP, Mazul AL. No survival benefit in never-smoker never-drinker patients with oral cavity cancer. Head Neck. 2023 Mar;45(3):567-577. doi: 10.1002/hed.27266. Epub 2022 Dec 16. PMID: 36524736; PMCID: PMC9898183.
  4. Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V; EHNS Executive Board. Electronic address: secretariat@ehns.org; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org; ESTRO Executive Board. Electronic address: info@estro.org. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1462-1475. doi: 10.1016/j.annonc.2020.07.011. Epub 2020 Oct 23. PMID: 33239190.
  5. Bagan J, Sarrion G, Jimenez Y. Oral cancer: clinical features. Oral Oncol. 2010 Jun;46(6):414-7. doi: 10.1016/j.oraloncology.2010.03.009. Epub 2010 Apr 18. PMID: 20400366.
  6. Cause-Specific Excess Mortality in Patients Treated for Cancer of the Oral Cavity and Oropharynx: A Population-Based Study van Monsjou HS, Schaapveld M, Hamming-Vrieze O, et al.Oral Oncology. 2016;52:37-44. doi:10.1016/j.oraloncology.2015.10.013.
  7. Dos Santos ES, Pérez-de-Oliveira ME, Normando AGC, Gueiros LAM, Rogatto SR, Vargas PA, Lopes MA, da Silva Guerra EN, Leme AFP, Santos-Silva AR. Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta-analysis. Head Neck. 2022 Dec;44(12):2925-2937. doi: 10.1002/hed.27193. Epub 2022 Sep 16. PMID: 36114663.
  8. Abadeh A, Ali AA, Bradley G, Magalhaes MA. Increase in detection of oral cancer and precursor lesions by dentists: Evidence from an oral and maxillofacial pathology service. J Am Dent Assoc. 2019 Jun;150(6):531-539. doi: 10.1016/j.adaj.2019.01.026. Epub 2019 Apr 25. PMID: 31030934.
  9. Zanoni DK, Montero PH, Migliacci JC, Shah JP, Wong RJ, Ganly I, Patel SG. Survival outcomes after treatment of cancer of the oral cavity (1985-2015). Oral Oncol. 2019 Mar;90:115-121. doi: 10.1016/j.oraloncology.2019.02.001. Epub 2019 Feb 15. PMID: 30846169; PMCID: PMC6417804.
  10. Treatment Outcomes of Squamous Cell Carcinoma of the Oral Cavity in Young Adults. Gamez ME, Kraus R, Hinni ML, et al. Oral Oncology. 2018;87:43-48. oi:10.1016/j.oraloncology.2018.10.014.
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