Head and neck squamous cell carcinomas

Last revised by Yuranga Weerakkody on 19 Jun 2024

Head and neck squamous cell carcinomas (HNSCC) are the most common histologic type of head and neck cancer. While the term may include any squamous cell carcinoma of the head and neck, common usage focuses on those of mucosal origin, i.e., squamous cell carcinoma of the upper aerodigestive tract, which is reflected in this article. Cutaneous squamous cell carcinoma is discussed separately.

Within the head and neck, different anatomic sites of disease have distinct clinical presentations, radiographic features, staging, and differential diagnoses, which are discussed separately:

Generalities irrespective of anatomic site will be discussed in this article.

The epidemiology of head and neck squamous cell carcinoma is substantially impacted by behavioral and environmental risk factors.

  • gender

    • overwhelmingly affecting males more commonly than females 6

  • age:

    • peak incidence between 50-70 years of age

    • although overall low, a rising incidence in younger patients is increasingly recognized, particularly in human papillomavirus positive oropharyngeal cancer 4

  • by location - changing overall incidence in recent decades 6:

    • oral cavity - decreasing, except oral tongue (increasing)

    • oropharyngeal - increasing

The most commonly implicated risk factors overall have historically been smoking tobacco and alcohol ingestion. Additional risk factors are being identified, including some strains of the human papillomavirus (HPV). Risk factors to be considered therefore include 1,2,4:

Human papillomavirus (HPV) is increasingly being recognized as an important risk factor for head and neck squamous cell carcinoma, having been recognized for some time in squamous cell carcinoma of the cervix. Some types are more strongly implicated (e.g. types 16, 18, and 31). Some anatomic sites are more strongly associated with HPV infection, chiefly the oropharynx, including palatine tonsils. HPV may be primarily responsible for up to 30% of oropharyngeal SCC, and 16% of hypopharyngeal SCC 1,2.

HPV-16 DNA has been isolated in up to 50% of oropharyngeal squamous cell carcinomas when their insertion into host cells results in deactivation of p53 and Rb genes, and overexpression of p16 gene 1,5. Overexpression of p16 is used as a surrogate histopathologic marker for HPV infection unless molecular testing (polymerase chain reaction for HPV DNA) is available.

Radiology has a great deal to offer patients with HNSCC. As imaging findings are site-specific, only general principles are described below. There are three main scenarios in which radiology is involved:

  1. diagnosis

  2. staging

  3. follow-up

Patients suspected clinically of having a squamous cell carcinoma are most frequently initially imaged with CT, which should be performed with intravenous contrast.

In the setting of a patient presenting with a neck mass, ultrasound and ultrasound-guided final needle aspiration with cytology are invaluable.

MRI is also increasingly used, although availability in many regions is limited.

It is important to remember that direct visualization with laryngoscopy is often able to identify thin superficial lesions that are inapparent on imaging 3.

Imaging is essential in staging local, regional, and distant disease and thus dictating management.

Head and neck squamous cell carcinomas are staged using the TNM staging system, which is differently defined by primary tumor site:

Most but not all of these primary tumor sites are associated with a similar scheme for cervical lymph node staging. In instances where nodes are suspicious but not clearly involved, ultrasound-guided fine-needle aspiration or FDG-PET may be used to clarify regional staging.

Imaging of patients who have undergone treatment is often challenging, as the combination of often extensive excisional and reconstructive surgery with superimposed radiotherapy distorts normal anatomy and alters tissue characteristics.

Additionally, a wide array of potential complications exist, including:

  • breakdown of surgical repair, e.g. fistula formation

  • radionecrosis, e.g. temporal lobe radionecrosis, mandibular osteoradionecrosis

Posttreatment response assessment and surveillance is most commonly performed with contrast-enhanced CT, preferably with FDG PET at least at the first (baseline) exam. Standardized reporting templates in this setting have been proposed by the American College of Radiology (NI-RADS).

Treatment is site and category-specific, but in general treatment options include combinations of surgical and oncological treatments. Definitive surgical management generally involves surgical excision of the primary tumor with or without unilateral or bilateral neck dissection, which may be followed by radiotherapy or chemo-radiotherapy depending on extent of disease and surgical outcome. Non-surgical oncological treatments include radiotherapy usually combined with chemotherapy. Immunotherapy options may increasingly play a role in head and neck squamous cell carcinoma treatment and this is an active area of research 7

Because of differing natural histories, HPV-positive and HPV-negative oropharyngeal cancers are staged and treated differently. HPV associated HNSCC tend to occur in younger patients and are categorized by rapid growth and early nodal spread. However, they are associated with a better response to conventional chemo-radiotherapy treatments and improved prognosis 5,7.  The estimated 5 year survival for oropharyngeal SCC is 90% in HPV positive cases, compared with 40% in HPV negative SCCs 7.

Prognosis depends not only on staging but also on location (even corrected for stage). Hypopharyngeal squamous cell carcinoma fares most poorly, with a 5-year survival for stage I-II of only 47%, compared to, for example, laryngeal squamous cell carcinoma of similar stage which has a 5-year survival of 79% 1.

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