Introduction
Head and neck cancers are the sixth most common group of malignancies worldwide. In the United States, the estimated incidence is 65,000 new cases per year, which are most commonly diagnosed among adults older than 50 years of age.
Geographic variations in the incidence and mortality rates of head and neck cancers are related to differences in patterns of exposure and behavior. Well-known risk factors include tobacco and alcohol consumption, betel chewing, and infection with high-risk human papillomavirus (HPV), specifically types 16 and 18, and Epstein–Barr virus (EBV).
Head and neck tumors can arise in the oral cavity, nasopharynx, hypopharynx, oropharynx, nasal cavity and paranasal sinuses, larynx, and salivary glands. Multiple histologies can be found in these sites, but more than 90% are squamous cell carcinomas (SCC). SCC is associated with aggressive behavior and high incidence of locoregional recurrence.
Several studies have reported an upward trend in the incidence of oropharyngeal cancer (OPC) worldwide. In the United States, HPV-related OPCs have risen since 1984. The most affected population are younger men with a history of multiple lifetime oral sex partners and without a long history of tobacco and alcohol consumption. Clinical presentation differs from the classic stereotype and is characterized by small tumors with bulky lymph nodal disease at diagnosis.
Evaluation of the Patient with Head and Neck Cancer
Patients diagnosed with head and neck cancers require a comprehensive evaluation by a multidisciplinary team consisting of head and neck surgeons, medical oncologists, radiation oncologists, plastic and reconstructive surgeons, dental surgeons, and speech pathologists.
Medical History
A complete medical history is collected, noting the onset and progression of symptoms and focusing on key risk factors that include tobacco and alcohol consumption, sun and environmental exposure, prior cancer history, number of sexual partners, immunosuppression, and other comorbidities. Family history and social circumstances are also recorded, as birthplace, ethnicity, and family support can play a role in treatment planning and rehabilitation. The rapid progression of symptoms suggests aggressive disease and may be an indication for emergency intervention.
Head and neck malignancies can have a major impact on patient´s activities of daily living, such as eating, speaking, swallowing, and breathing, which can affect performance status. Performance status is critical for assessing a patient’s ability to tolerate treatment. A complete pretreatment assessment should include an evaluation of nutritional and dental status, focusing on the need for supplemental nutrition (orally or using a gastrostomy tube), eradication of periodontal disease, or dental extraction.
Clinical Examination
A comprehensive head and neck examination should be performed to address the primary tumor site and to search for second primaries, which can be present in 2%–5% of patients. , Examination should be performed with the patient sitting upright and begins with the evaluation of the skin of the scalp, face, and neck, followed by palpation of the thyroid, parotid gland, neck nodal basins, and abnormal masses. Testing of cranial nerve function should be included routinely, as well as rhinoscopy and external ear examination. The examination of the oral cavity should include observation of mucosal lesions, dental care, and palpation of the tongue, floor of mouth, base of tongue, and tonsils.
Endoscopic assessment can be done with a mirror or with a flexible fiberoptic endoscopy, which will include visualization of the nasal cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Functional tests should be done to evaluate vocal cord mobility.
Imaging Examination
Modern imaging has dramatically enhanced diagnosis and staging of head and neck cancers. Different modalities include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Modality selection is affected by multiple factors, including availability, coverage, experienced radiologists, primary location of the tumor, and stage of the disease.
US is useful for the assessment of superficial or soft-tissue lesions located in the thyroid or parotid gland, it is sensitive for the detection of lymph node metastasis, but it is operator-dependent and requires expertise. CT is widely available, allows rapid image acquisition, and reduces artifacts related to respiration and swallowing; it is best suited for defining primary tumor and identifying bone invasion, and can be used for guiding tissue biopsy. MRI offers a superior soft tissue contrast and is preferred when the tumor needs to be differentiated from adjacent soft tissue structures, including tumors arising in the sinonasal region, oral cavity, and salivary glands. PET/CT is frequently used to evaluate advanced head and neck cancers, regional and distant metastases, and post treatment response to chemoradiotherapy.
Biopsy
Tissue confirmation of the diagnosis is necessary before any cancer treatment; samples can be obtained using fine needle aspiration, core needle, or surgical biopsy. Care must be taken to obtain representative tissue samples that allow accurate histological classification.
Staging
Correctly staging the disease is an essential component of the oncologic evaluation. It allows a universal understanding of the disease and influences decision making. The tumor–node–metastasis (TNM) staging system, developed by the American Joint Committee on Cancer (AJCC), is the most commonly used staging system. Information needed to stage patients is obtained from physical examinations, laboratory tests, imaging exams, pathology results, and surgical reports. T stage is based on the anatomic location and size of the primary tumor. N indicates regional disease and considers the number and location of regional lymph nodes. M indicates the presence of distant metastasis. These are translated to an overall stage classification ranging from I to IV. Early-stage disease includes stages I and II, and advanced stage disease stages III and IV.
The recent eighth edition of the AJCC staging manual introduces significant changes to the head and neck section. The most significant updates are the creation of a separate staging classification for HPV-related OPC, the addition of depth of invasion (DOI) in the T category for oral cavity carcinoma, the incorporation of skin cancer staging (other than melanoma and Merkel cell carcinoma) in the head and neck chapter, the change in the T and N status in nasopharyngeal cancers, and the inclusion of the extranodal extension feature to the N category.
The T0 classification is used when the primary tumor is not known. More than 90% of unknown primary tumors are HPV- or EBV-positive, which is why T0 is only used for HPV-related OPCs and tumors located in the nasopharynx. T0 is not used for HPV-negative OPCs and other non-HPV-related cancers located in the oral cavity, larynx, hypopharynx, and paranasal sinus.
In this chapter, we will address staging by anatomical site, excluding tumors arising from the thyroid gland.
Oral Cavity
The oral cavity extends from the skin vermilion junction of the lips to the junction of the hard and soft palates superiorly, the circumvallate papillae inferiorly, and the anterior tonsillar pillars laterally. Different subsites in the oral cavity include the lips, alveolar ridge, buccal mucosa, retromolar trigone, hard palate, floor of mouth, and two-thirds of the anterior tongue. Table 23.1 summarizes the T stages for primary tumors of the oral cavity.
| T Category | T Criteria |
|---|---|
| Tis | Carcinoma in situ |
| T1 | Tumor ≤2 cm with DOI ≤5 mm |
| T2 | Tumor ≤2 cm with DOI >5 mm or tumor >2 cm but ≤4 cm with DOI ≤10 mm |
| T3 | Tumor >2 cm and ≤4 cm with DOI >10 mm or tumor >4 cm with DOI ≤10 mm |
| T4a | Moderately advanced local disease Tumor >4 cm with DOI >10 mm or tumor invades adjacent structures only (e.g., through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of the face) a |
| T4b | Very advanced local disease Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery |
a Superficial erosion of bone/tooth socket (alone) by a gingival primary is not sufficient to classify a tumor as T4.
The main change in oral cavity clinical and pathological staging was the inclusion of DOI based on the results of a large international collaborative study of oral cavity cancer. This study showed that DOI was significantly associated with disease-specific survival, supporting the relevance of this feature as a mark of biological behavior.
Clinical determination of DOI is challenging and requires the clinician to distinguish between a thick, exophytic tumor from one that is ulcerated and infiltrative; this information is used in conjunction with radiological features to plan treatment.
Of note, pathological DOI should be measured from the level of the basal membrane of the closest adjacent mucosa to the deepest point of tumor invasion.
Nasopharynx
The nasopharynx represents a transitional area between the nasal cavity and the oropharynx. It includes the vault, the lateral walls (formed by the orifices of the Eustachian tube superiorly and the superior constrictor inferiorly), the posterior wall, and the superior surface of the soft palate. Table 23.2 summarizes the T stages for primary tumors of the nasopharynx.
| T Category | T Criteria |
|---|---|
| T0 | No tumor identified, but EBV-positive cervical node(s) involvement |
| Tis | Carcinoma in situ |
| T1 | Tumor confined to the nasopharynx or extension to the oropharynx and/or nasal cavity without parapharyngeal involvement |
| T2 | Tumor with extension to parapharyngeal space and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles) |
| T3 | Tumor with infiltration of bony structures at skull base, cervical vertebra, pterygoid structures, and/or paranasal sinuses |
| T4 | Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle |
Oropharynx
The oropharynx includes the soft palate, tonsils, base of the tongue, and pharyngeal walls bounded superiorly by the nasopharynx and inferiorly by the pharyngoepiglottic fold. It extends from the level of the soft palate superiorly to the level of the hyoid bone inferiorly. Tables 23.3 and 23.4 summarize the T stages for primary HPV-related OPC and for primary non-HPV-related OPC, respectively.
| T Category | T Criteria |
|---|---|
| T0 | No primary tumor identified |
| T1 | Tumor ≤2 cm in greatest dimension |
| T2 | Tumor >2 cm but ≤4 cm in greatest dimension |
| T3 | Tumor >4 cm in greatest dimension or extension to lingual surface of the epiglottis |
| T4 | Moderately advanced local disease Tumor invades the larynx, extrinsic muscle of the tongue, medial pterygoid, hard palate, mandible, or beyond a |
a Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx.
| T Category | T Criteria |
|---|---|
| Tis | Carcinoma in situ |
| T1 | Tumor ≤2 cm in greatest dimension |
| T2 | Tumor >2 cm but ≤4 cm in greatest dimension |
| T3 | Tumor >4 cm in greatest dimension or extension to lingual surface of the epiglottis |
| T4a | Moderately advanced local disease Tumor invades the larynx, extrinsic muscle of the tongue, medial pterygoid, hard palate, or mandible a |
| T4b | Very advanced local disease Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery |
a Mucosal extension to lingual surface of the epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx.
The epidemiological transition in oropharyngeal disease led to one of the major changes in the staging system. The eighth edition adds the overexpression of the tumor suppressor protein p16, a surrogate biomarker for HPV infection, as an independent prognostic feature. OPC is now staged based on the overexpression of p16. The Tis and T4b categories are no longer used for HPV-related OPC because they lack applicability to the disease.
Hypopharynx
The hypopharynx starts at the level of the hyoid bone and ends at the lower border of the cricoid cartilage. It is essentially a muscular line tube. Three areas can be distinguished: pyriform sinus, lateral and posterior pharyngeal walls, and postcricoid area. Table 23.5 summarizes the T stages for primary tumors of the hypopharynx.
| Primary Tumor | T Criteria |
|---|---|
| Tis | Carcinoma in situ |
| T1 | Tumor limited to one subsite of the hypopharynx and /or ≤2 cm in greatest dimension |
| T2 | Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures >2cm but ≤4 cm in greatest dimension, without fixation of hemilarynx |
| T3 | Tumor >4 cm in greatest dimension or with fixation of the hemilarynx or extension to esophagus |
| T4a | Moderately advanced local disease Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue a |
| T4b | Very advanced local disease Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures |
a Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat.
Larynx
The larynx spans from vertebral level C3 to C6, suspended from the hyoid bone and continuous with the trachea. It is composed of six cartilages: three large, unpaired (cricoid, thyroid, and epiglottis) and three paired (arytenoid, corniculate, and cuneiform). It is subdivided into three anatomic regions: supraglottis, glottis, and subglottis. Supraglottic subsites include the epiglottis, arytenoids, aryepiglottic folds, and false vocal cords. Glottic subsites include the true vocal cords and anterior and posterior commissures. Table 23.6 summarizes the T stages for primary tumors of the larynx.
| T Category | Supraglottis | Glottis | Subglottis |
|---|---|---|---|
| T1 | Tumor limited to one subsite of supraglottis, with normal vocal cord mobility | T1 Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility T1a limited to one vocal cord, with normal mobility T1b involves both vocal cords, with normal mobility | Tumor limited to the subglottis |
| T2 | Tumor invades mucosa of more than one adjacent subsite of the supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx | Tumor extends to the supraglottis and/or subglottis, and/or with impaired vocal cord mobility | Tumor extends to vocal cord(s), with normal or impaired mobility |
| T3 | Tumor limited to the larynx, with vocal cord fixation, and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage | Tumor limited to the larynx, with vocal cord fixation, and/or invasion of paraglottic space and/or inner cortex of the thyroid cartilage | Tumor limited to the larynx, with vocal cord fixation, and/or invasion of paraglottic space and/or inner cortex of the thyroid cartilage |
| T4a | Moderately advanced local disease Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) | Moderately advanced local disease Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, cricoid cartilage, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus) | Moderately advanced local disease Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) |
| T4b | Very advanced local disease Tumor invades the prevertebral space, encases carotid artery, or invades mediastinal structures | Very advanced local disease Tumor invades the prevertebral space, encases carotid artery, or invades mediastinal structures | Very advanced local disease Tumor invades the prevertebral space, encases carotid artery, or invades mediastinal structures |
Nasal Cavity and Paranasal Sinuses
Tumors of the nasal cavity and paranasal sinuses are grouped together in this category. The nasal cavity is limited by several bones. The superior boundary, or roof, is formed by the nasal bones, cribriform plate, and sphenoid bone. The floor is formed by the hard palate anteriorly and nasopharynx posteriorly. The lateral margins are the medial walls of the maxillary sinus.
Paranasal sinuses include the maxillary, frontal, ethmoid, and sphenoid sinuses. The maxillary sinus is a pyramidal cavity in the body of the maxilla. It is bounded superiorly by the orbital floor, inferiorly by the hard palate, posteriorly by the pterygoid plates and pterygopalatine fossa, and laterally by the pterygoid muscles. The frontal sinuses are located behind the superciliary arches and along and above the anterior aspect of the ethmoid sinus. The ethmoid sinus lies in the upper part of the nasal cavity between the orbits. The sphenoid sinus is posterior to the ethmoid sinus.
Tables 23.7 and 23.8 summarize the T stages for primary tumors of the nasal cavity and ethmoid sinus and for primary tumors of the maxillary sinus, respectively.
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