Mehrnaz Fayazi (April 8, 2025)
Head and neck cancers can start in areas like the mouth, throat (pharynx and larynx), nose, sinuses, and salivary glands. In 2020, approximately 65,630 new cases of oral, pharyngeal, and laryngeal cancers were expected in the United States. Over 90% of these cases were expected to be oral squamous cell carcinomas (SCC). (1). This cancer is the seventh most common cancer in the world, with an estimated 700,000 new cases diagnosed annually (1, 2).
Demographics:
The majority (95%) of oral cancers occurs in individuals aged 40 and above, with men more likely affected (male-to-female ratio is 1.43 to 1). However, a rising number of SCC cases are being observed in younger patients under 40 (4).
Location:
In patients above 40 years old, the cheek soft tissue (buccal mucosa) is the most commonly affected site for oral cancer, while the gums (gingiva) and tongue are also frequently involved (3, 4). In patients under 40 years old, the tongue is the most affected site. Cancers of the tongue are often linked to trauma or undetected tissue conditions that carry an increased risk for developing cancer (a.k.a. potentially malignant disorders) (3, 5).
Risk Factors:
Studies have shown that 90% of individuals affected by SCCs have had at least one of the following risk factors (3):
- smoking or alcohol consumption: 75–85% of cases are linked to these habits
- poor oral hygiene
- mechanical irritation from faulty dental work
- human papillomavirus (HPV) infection (especially linked to cancers in the back of the mouth (oropharynx))
- Epstein–Barr virus (EBV) infection (especially linked to nasopharyngeal carcinoma)
(1, 2, 6)
In individuals affected by SCCs under 40 years old, and especially females, there may be no known underlying cause like smoking. It is thought that repeated injury (trauma) or undetected predisposing factors may be responsible for these cancers.(3, 5).
Signs And Symptoms:
- Lump in neck: should be evaluated by a specialist within two weeks
- Swollen glands in the neck: especially when accompanied by symptoms like fever, night sweats, itchy skin, unexplained weight loss, or pain when drinking alcohol.
- Difficulty swallowing food or drink: should be investigated with an endoscopy within 2 weeks.
- Hoarseness (raspy voice): If this lasts longer than usual in people over 45 should prompt referral to rule out laryngeal cancer.
- Lumps, ulcers, or red/red-and-white patches in the mouth or lips: If they last more than 3 weeks and are not explained by other causes (7).
Although many individuals notice symptoms, these are often mistaken for benign conditions or managed through self-treatment using herbal remedies, leading to significant delays in diagnosis. A key cultural factor contributing to this issue is the lack of routine dental check-ups, with over 80% of patients not attending biannual dental examinations (8).
Diagnosis:
A comprehensive diagnostic approach for head and neck cancers involves multiple steps,
- detailed history and physical examination
- Imaging: CT and MRI scans are commonly used to evaluate tumor size and lymph node involvement, while FDG-PET/CT is particularly effective for detecting metastases or recurrence
- Biopsy: the most reliable way to confirm a diagnosis
- Intraoral ultrasonography: helpful when it comes to assessing how deep the tumor has grown (1, 2, 6)
Treatment:
Treatment depends on the cancer’s location, size, and stage.
Stage I–II (about 30–40% of cases): Surgery or radiation therapy (RT)
- Surgery is common for mouth cancers
- RT is preferred for throat or nasopharynx cancers.
Stage III–IV (resectable): Surgery with possible neck dissection and reconstruction.
Stage III–IV (unresectable/refusing surgery): Combination of Chemoradiotherapy and immunotherapy and radiation
- Radiotherapy:
Includes brachytherapy and external beam radiotherapy like IMRT. Chemoradiotherapy is preferred in high-risk or inoperable cases. Postoperative chemoradiotherapy is advised for patients with high-risk features, such as positive margins or extranodal extension
- Drug Therapy:
Cisplatin-based regimens are standard for concurrent or adjuvant therapy. Alternatives such as carboplatin with 5-fluorouracil or weekly low-dose cisplatin may be used for patients who cannot tolerate high-dose therapy. Immunotherapy is used in metastatic or recurrent cancers (1, 2, 6).
Common Side Effects:
- Dry mouth
- Difficulty swallowing
- Oral mucositis (mouth sores)
Pain relief mouthwashes or medications like gabapentin may help to mitigate this effect (1).
Follow up:
Ongoing follow-up are crucial, as most recurrences happen within the first three years after treatment of cancers (1).
- every 2–3 months in years 1–2
- every 6 months in years 3–5
- annually after 5 years
- node-positive cases: PET/CT scans 3 months post-treatment
- history of smoking: annual chest CT (to identify secondary lung cancers) (1, 6).
Supportive Care
- Nutritional support is critical due to the high risk of weight loss and swallowing difficulties. Malnutrition and sarcopenia significantly impact survival in OSCC.
- Speech and language therapy can help restore communication and swallowing functions.
- A dental evaluation before and after radiation therapy is necessary to prevent complications like osteoradionecrosis and dental caries (9).
Innovations:
Recent advances in oral squamous cell carcinoma (OSCC) research have introduced several promising innovations that could significantly enhance early detection, prognosis, and treatment planning.
One notable development is the identification of microRNA-21 as a promising non-invasive biomarker for diagnosing and predicting outcomes in oral tongue and buccal squamous cell carcinomas. Its elevated levels are associated with advanced stages, poor prognosis, and metastasis. Detectable in saliva and blood, miR-21 supports the use of liquid biopsy for early detection, monitoring, and personalized treatment (10).
Alongside advances in molecular biomarkers, the concept of field cancerization (FC) is becoming more clinically important. FC means that even areas of the mouth that appear healthy can carry hidden changes at the cellular level, often due to long-term exposure to carcinogens like tobacco, betel nut, and alcohol. These changes can raise the risk of new cancers developing, even after the original tumor has been treated. Regions such as the buccal mucosa, tongue, floor of the mouth, and gingivobuccal sulcus that are commonly exposed to these substances, are especially at risk. This underlines the importance of long-term follow-up and a more comprehensive approach to treatment and prevention (11).
Key Take away:
Personalized treatment planning, supportive care, and modern therapies like immunotherapy and targeted agents are all integral to achieving the best possible outcomes(1)
About the author:
Dr. Mehrnaz Fayazi is a dentist and researcher with a focus on oral cancer and head and neck pathology. She is passionate about early detection, patient education, and advancing care through evidence-based practices. She is a volunteer article contributor to The Dental Institute.
References:
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(2) Machiels JP LC, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020;31(31):1462–75.
(3) Thankappan S, Nedumpillil S, Thomas V. Clinicopathologic features and risk factors associated with oral squamous cell carcinoma (OSCC): A comprehensive descriptive study analyzing the burden of OSCC in a tertiary-level hospital in North Kerala, India. Indian J Cancer. 2023;60(4):534-41.
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(5) Huang X WT, Chen C, Qiu H, Wu Y, Li C, Wang Z. Unique clinical features and prognostic risk factors of oral squamous cell carcinoma in patients under 30 years old. Clinical Oral Investigations. 2025.
(6) Kurita H, Uzawa N, Nakayama H, Abe T, Ibaraki S, Ohyama Y, et al. Japanese clinical practice guidelines for oral cancer, 2023. Int J Oral Maxillofac Surg. 2025;54(5):461-76.
(7) Excellence NIfHaC. Recognizing, investigating and referring people with symptoms of suspected cancer London. NICE guideline NG12. London: NICE; 2015 25 June 2015.
(8) Pakravan F, Abbasi F, Garshasbi MA, Isfahani MN. Relationship between oral cancer stage and elapsed time from the onset of signs and symptoms to diagnosis and treatment. Cancer Treat Res Commun. 2021;28:100428.
(9) Buscemi P, Randazzo C, Buscemi C, Barile AM, Finamore E, Caruso R, et al. Nutritional factors and survival in a cohort of patients with oral cancer. Front Nutr. 2025;12:1530460.
(10) Hussain F, Nair A, Tharakan A. MicroRNA-Based Markers of Oral Tongue Squamous Cell Carcinoma and Buccal Squamous Cell Carcinoma. Cureus. 2025;17(2):e79733.
(11) Peralta-Mamani M T-PÁ, Tucunduva RMA, Rubira CMF, Santos PSS, Honório HM, Rubira-Bullen IRF. Occurrence of field cancerization in clinically normal oral mucosa: A systematic review and meta-analysis. Archives of Oral Biology. 2022;143:105544.