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Head and neck cancers include neoplasms of the nose/nasal passages, mouth/oral cavity, pharynx, salivary glands, and larynx.[1] They comprise the sixth most common malignancies worldwide, representing more than 550,000 cases and 300,000 deaths annually.[2] Males are disproportionately affected, with male-to-female ratios ranging from 2:1 to 4:1.[2]
The majority of head and neck tumors are squamous cell carcinomas (SCCs) (90%)[2-4]—except for cancers of the skin (basal cell carcinomas [BCCs]),[4] thyroid gland (papillary, follicular, medullary, anaplastic thyroid tumors) (not discussed),[5] and salivary gland (adenocarcinomas, adenoid cystic carcinomas, mucoepidermoid carcinomas).[3] Lymphoma (Hodgkin and non-Hodgkin) also occurs.[5]
The image shows a patient with locally advanced SCC of the upper lip.
Image courtesy of Wikimedia Commons/Phoenix119.
In the United States, cancers of the head and neck account for about 3%-5% of all malignancies,[1,3,4] representing 48,000-59,000 cases each year, with approximately 13,000 patients dying from these diseases annually.[3,4,6] However, the overall incidence and mortality of head and neck malignancies has declined or stabilized over the past 2 decades (shown).[1]
Most patients with tumors of the head and neck are male and aged 50-70 years, but the incidence in female smokers and in younger patients is increasing.[7] Among racial and ethnic groups, black individuals are affected more commonly than white, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic persons.[1]
Graphs courtesy of the National Cancer Institute (NCI).[1] Data source: Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics.
The most common sites of head and neck cancer are the following[2,7,8]:
Less common sites of head and neck cancer include the following[2,7,8]:
The image shows a patient with recurrent and locoregional spread of exophytic SCC of the right face via direct extension from the oropharyngeal region.
Image courtesy of Jerjes W, Upile T, Petrie A, et al. Head Neck Oncol. 2010;20;2:9. [Open access.] PMID: 20406474, PMC2882907.
Tobacco (including smokeless tobacco) (75%-85%)[3,6-8] and alcohol use, alone or in combination, are the most important risk factors for the development of head and neck cancers.[2-4,6-8] Male sex is a risk factor, although the incidence is rising in females, as discussed earlier. In addition, infection with certain strains of human papillomavirus (HPV),[1,7] particularly HPV16 and HPV18, causes more than half of all cases of oropharyngeal cancer.[1,9]
Other risk factors for cancers of the head and neck include the following:
Image of tobacco snuff courtesy of Dreamstime/Robhainer (left); image of oral leukoplakia courtesy of Wikimedia Commons/Michael Gaither and dozenist.
Cutaneous head and neck cancers are a heterogeneous group of tumors.[10,11] Due to chronic sun exposure, the head and neck region is prone to development of skin cancers. Common types include SCC, BCC (shown), and malignant melanoma.[11]
Image courtesy of Wikimedia Commons/Klaus D. Peter.
Laryngeal cancer is the second most common malignancy of the head and neck,[3] with the majority being of squamous cell histology.[12] SCC subtypes include keratinizing and nonkeratinizing, and grades that range from well differentiated to poorly differentiated.[12,13] A variety of non-SCC laryngeal tumors also occur (not discussed).[12]
An estimated 60%-65% of laryngeal tumors occur in the glottic region, 30%-35% in the supraglottic region (often presenting as locally advanced disease owing to a rich lymphatic network), and about 5% in the subglottic region.[14]
Images of laryngectomy specimens from patients with laryngeal cancer courtesy of Wikimedia Commons/Paweł Kuzniar.
Oral and oropharyngeal neoplasms typically affect patients older than 50 years.[15] Over 60% of new cases of oropharyngeal cancer are associated with HPV,[5] and these malignancies are about 3-5 times as common in men than in women.[16,17]
An estimated 40% of intraoral SCCs originate on the floor of the mouth or the lateral and ventral tongue surfaces.[15] Precancerous lesions of the oropharynx include leukoplakia (most common; diagnosis of exclusion) (see slide 4, right image), erythroplakia, and mixed erythroleukoplakia.[18]
The oropharyngeal region is rich in lymphatics, which facilitates cervical lymph node metastasis.[16] Retropharyngeal lymph nodes are particularly at risk for nodal spread in oropharyngeal cancer.[17]
Image of carcinoma of the gingiva courtesy of Wikimedia Commons/Bionerd.
Unlike other tumors of the head and neck, nasopharyngeal cancer does not appear to be linked to excessive tobacco use or moderate alcohol consumption (≤15 drinks per week).[3,19] These malignancies occur more frequently in Asia, particularly southeast China, the Mediterranean, and Africa; other significant risk factors include EBV exposure, dietary intake of nitrites and salted fish, and hereditary factors.[3,19,20]
The T2-weighted, fat-suppressed, fast-spin-echo (FSE) anatomic magnetic resonance images (MRIs) are from a patient with nasopharyngeal carcinoma. Regions of interest (ROIs) were drawn on the primary tumors (1), metastatic node (2), spinal cord (3), and muscle (4).
Images courtesy of Yuan J, Yeung DK, Mok GS, et al. PLoS One. 2014;23;9(1):e87024. [Open access.] PMID: 24466318, PMCID: PMC3900693.
The majority of tumors of the paranasal sinuses are of unknown etiology, and they usually present as advanced disease, typically with poor cure rates (<50%).[14,21,22] As with most head and neck cancers, SCC is the most frequent cellular type of malignant tumor in the nose and paranasal sinuses,[21] but adenocarcinomas may also occur.[22]
The most common paranasal sinus malignancies are cancers of the maxillary sinus; less common are tumors of the ethmoid sinuses, nasal vestibule, and nasal cavity.[3,14,21] Even more rare are neoplasms of the sphenoid and frontal sinuses.[21] Papillomas are distinct entities that develop within the bony confines of the sinuses.[21] These tumors are usually benign and asymptomatic, but they may undergo malignant transformation, eroding and invading adjacent structures.
The contrast-enhanced computed tomography (CT) scans reveal (a) a right nasal cavity tumor with invasion of the right maxillary sinus and frontal sinus, with (b) invasion of the right orbit and destruction of the medial orbital wall. This patient was later determined to have basaloid SCC of the nasal cavity.
Images courtesy of Takamatsu S, Yamamoto K, Kondou T, et al. J Med Case Rep. 2014;8:123. [Open access.] PMID: 24716457, PMCID: PMC4000152.
In the United States and Canada, 65%-85% of hypopharyngeal carcinomas involve the pyriform sinuses, 10%-20% involve the posterior pharyngeal wall, and 5%-15% involve the postcricoid area.[23] Nearly all these tumors are mucosal SCCs, and about 25% of cases may consist of multiple primary tumors, potentially attributable to field cancerization from chronic exposure to carcinogens. In general, hypopharyngeal neoplasms have a tendency to be aggressive, remaining asymptomatic until they are advanced.[5,23]
Upper hypopharyngeal malignancies appear to be associated more with heavy drinking and smoking, whereas the lower hypopharyngeal, or postcricoid, cancers are more often associated with nutritional deficiencies.[23] Earlier reports suggested a link between Plummer-Vinson syndrome (sideropenic anemia, epithelial changes of the aerodigestive tract) and other nutritional deficiencies in women (eg, low vitamins A and E); however, currently, excessive use of alcohol and tobacco is more likely to increase the risk of hypopharyngeal cancer among women than are deficiency diseases.[3,23]
The MRIs were obtained from a patient with advanced hypopharyngeal carcinoma. Images A and B are, respectively, axial T2-weighted and axial nonenhanced T1-weighted images depicting lesions involving the dorsal and right lateral pharyngeal wall, avoiding the retropharyngeal space. Note the intact prevertebral fat, clearly obtainable on the T1-weighted image (triple arrows). Image C is an axial postcontrast T1-weighted image with fat suppression at the level of the tongue base; the tumor has infiltrated the tongue base and crossed the midline to the opposite side. Bilateral metastatic lymph nodes can be seen (arrows).
Images courtesy of Godeny M. Cancer Imaging. 2014;14:15. [Open access.] PMID: 25608735, PMCID: PMC4331821.
Salivary gland cancers includes tumors of the parotid gland (85%), the submandibular and minor salivary glands, and sublingual glands (1%).[25] These tumors are a rare and morphologically and clinically diverse group of tumors, which may present significant diagnostic and management challenges.[24] In addition, the etiology of most salivary gland tumors cannot be determined, although exposure to ionizing radiation has been implicated.[24]
Most salivary gland tumors are benign (75%-80%),[14,25] but malignant salivary gland neoplasms account for approximately 3%-5% of all head and neck cancers and typically affect those aged 60s-70s.[24] An estimated 20%-25% of parotid tumors, 35%-40% of submandibular tumors, 50% of palate tumors, and over 90% of sublingual gland tumors are malignant.[24] Histologic diagnosis via biopsy or excision is required to exclude malignant behavior.
The intraoral image shows an exophytic and endophytic growing tumor of the left buccal mucosa (3 × 2 × 1.5 cm3) with indiscernible borders.
Image courtesy of Ettl T, Kleinheinz J, Mehrotra R, Schwarz S, Reichert TE, Driemel O. Head Face Med. 2008;4:16. [Open access.] PMID: 18667060, PMCID: PMC2515301.
Signs/symptoms of head and neck tumors may be vague and are often dependent on the site of origin:
The photograph shows a patient with a right parotid gland tumor presenting as a mass.
Image courtesy of Wikimedia Commons/N Raveender.
As with other types of malignancies, workup of head and neck tumors include obtaining a detailed history (eg, tobacco and alcohol use, potential environmental/occupational/industrial exposures), as well as a thorough physical examination, with particular focus on the head and neck region.[3,5,14] Evaluate the oral cavity and regional lymph node basins.
Diagnostic studies include brush or incisional biopsy for oral lesions and fine-needle aspiration (FNA) biopsy for neck masses.[3,7,14] Other biopsy procedures include punch/cup forceps biopsy of mucosal lesions, and open biopsies, which are performed when FNA findings are nondiagnostic and the clinical evaluation results remain unclear, by a surgeon able to undertake an immediate definitive surgical treatment, as needed.[5]
The images are from a patient with oral cancer. Image a shows the appearance of the lesion at the time of diagnosis; image b was obtained at the time of biopsy of the suspected area, and images c are histologic images showing moderately differentiated oral SCC.
Images courtesy of Jane-Salas E, Lopez-Lopez J, Rosello-Llabres X, Rodriguez-Argueta OF, Chimenos-Kustner E. Med Oral Patol Oral Cir Bucal. 2012;17(1):e23-8. [Open access.] PMID: 21743414, PMCID: PMC3448182.
Imaging studies in patients with suspected head and neck neoplasms include the following[3,5,7,14]:
Refer patients with signs/symptoms that persist for more than 2-3 weeks to a head and neck specialist for flexible fiberoptic laryngoscopy.[7]
Sonograms of a pleomorphic adenoma of the left parotid gland courtesy of Rudack C, Jorg S, Kloska S, Stoll W, Thiede O. Head Face Med. 2007;3:19. [Open access.] PMID: 17407595, PMCID: PMC1852309.
Images A-C are axial PET-CT scans from a patient with hypopharyngeal carcinoma and bilateral metastatic lymph nodes. Cancer on the dorsal pharyngeal wall and suspected metastatic lymph nodes in the deep cervical lymphatic regions bilaterally are noted.
Images D-F are multiplanar contrast-enhanced-CT scans in the axial, sagittal, and coronal planes, respectively, from the same patient. A mass in the dorsal wall of the hypopharynx, affecting the integrity of the fat layer in the prevertebral space, is detectable in the sagittal plane (E) (arrow). The coronal CT scan (F) shows metastatic lymph nodes bilaterally (arrows) with colliquation (liquefaction).
Images courtesy of Godeny M. Cancer Imaging. 2014;14:15. [Open access.] PMID: 25608735, PMCID: PMC4331821.
These images are from a patient with oral SCC. The intraoral photograph (a) shows the lesion on the left (patient's right side). The ortopanoramic radiograph (b) was obtained following ablative surgery of the tumor.
Images courtesy of Pompa G, Saccucci M, Di Carlo G, et al. BMC Oral Health. 2015;15:5. [Open access.] PMID: 25599761, PMCID: PMC4324417.
These axial MRIs were obtained from an elderly patient with nasopharyngeal carcinoma and cranial nerve invasion. Image A is an enhanced T1-weighted image with fat suppression showing the effacement of the left gasserian ganglion (wide arrow). Image B is a proton density (PD)–weighted image revealing the normal right gasserian ganglion (thin arrow).
Images courtesy of Zong J, Lin S, Chen Y, et al. PLoS One. 2014;9(6):e100571. [Open access.] PMID: 24963626, PMCID: PMC4070924.
The American Joint Committee on Cancer (AJCC)–derived tumor, node, metastasis (TNM) staging system is used for staging head and neck cancers.[5,7,14] The results of the workup determine the TNM staging, which vary by the anatomic site of the lesions.
The image shows a portion of the TNM classification for lip and oral cavity malignancies.
Image courtesy of the National Comprehensive Cancer Network (NCCN).[14]
Once the diagnosis of head and neck cancer has been established, treatment is tailored to the site of origin of the primary tumor. A multidisciplinary management team, including a head and neck surgical oncologist, and multidisciplinary approach are essential for optimal therapy and follow-up.[14]
Traditionally, single-modality surgery or radiation therapy has been the treatment of choice for most types of head and neck cancer, particularly in early-stage disease; multimodality therapy is generally recommended for advanced disease.[3,5,7,14] Nasopharnygeal cancers are a partial exception (often not amenable to surgical resection) owing to their location and extent of involvement, with concurrent chemotherapy and radiation therapy followed by adjuvant chemotherapy being the standard of care.[19]
Laryngeal anatomy is shown. Clinical target volumes for intensity-modulated radiotherapy (IMRT) for laryngeal cancer are defined on the basis of cancer extension in the larynx; therefore, laryngeal anatomy, including the parapharyngeal space, must be considered in cases of suspected local extension and/or retro/parapharyngeal node involvement.
Images courtesy of Merlotti A, Alterio D, Vigna-Taglianti R, et al, for the Italian Association of Radiation Oncology. Radiat Oncol. 2014;9:264. [Open access.] PMID: 25544268, PMCID: PMC4316652.
Surgery
Surgery is the mainstay of treatment for most head and neck SCCs, and surgical management has improved over time because of advances in anesthesia, the advent of antibiotics and blood banking, and the introduction of new techniques for reconstruction.
The goal is cure with preservation of function and limiting of cosmetic consequences. Minimally invasive procedures may reduce morbidity, and transoral resection with robotic, endoscopic, or direct access surgery may provide some advantages over traditional methods.[14]
An example of a chart overview of organ preservation strategies for patients with laryngeal cancer is shown.
Image courtesy of Chawla S, Carney AS. Head Neck Oncol. 2009;1:12. [Open access.] PMID: 19442314, PMCID: PMC2686690.
This photograph shows a radical neck dissection. The black arrow indicates the resected internal jugular vein. The blue arrow indicates the resected spinal accessory nerve.
Image courtesy of Popescu B, Bertesteanu SV, Grigore R, Scaunasu R, Popescu CR. J Med Life. 2012;5(4):410-3. [Open access.] PMID: 23346241, PMCID: PMC3539843.
Radiation therapy
Radiation therapy is occasionally used in conjunction with surgery in the management of head and neck malignancies. Relatively recently, targeted therapies against specific cellular receptors and signaling molecules have emerged, with the potential to affect future management of head and neck cancers.
External-beam radiation therapy (EBRT) (most common) is typically administered in the form of photon beams (x-rays, gamma rays). Some methods of EBRT include the following[26]:
Internal radiation therapy (IRT) (brachytherapy) and systemic radiation therapy are also management options.[26]
The fluorine-18 fluorodeoxyglucose (18FDG)-PET scans were obtained from the same patient with basaloid SCC of the nasal cavity who was discussed in slide 9. Image a shows uptake of the radionuclide by the tumor. Image b was obtained 2 years after the patient completed proton beam therapy. No evidence of tumor recurrence is noted.
Image courtesy of Takamatsu S, Yamamoto K, Kondou T, et al. J Med Case Rep. 2014;8:123. [Open access.] PMID: 24716457, PMCID: PMC4000152.
This image shows the isodose curve following CT-guided permanent brachytherapy with iodine-125 (125I) seed implantation in a patient with recurrent head and neck cancer. The inner red curve represents gross tumor volume (GTV). The ellipses are isodose lines of 160, 140, 120, and 90 Gy from the inside out, respectively.
Image courtesy of Jiang YL, Meng N, Wang JJ, et al. Radiat Oncol. 2010;5:68. [Open access.] PMID: 20673340, PMCID: PMC2919543.
Chemotherapy
Chemotherapy is an essential component in curative multimodality management for locally advanced head and neck cancer. In particular, concurrent regimens of chemotherapy with radiation therapy are standard treatment in the management of nasopharyngeal malignancies and in cases of locally advanced disease or high-risk pathology.[3,14] Different strategies and regimens exist for on the basis of different anatomic sites and tumoral extent.
Image courtesy of the National Institute of Health/Bill Branson.
Similar to other malignancies, prognostic factors for head and neck cancers include stage, tumor size and extent, location, etiology, and whether the disease is primary or recurrent.[7]
A 2016 study indicated that in addition to stage, the following are also prognostic factors for unresectable locally advanced head and neck cancer treated with combination radiochemotherapy[27]:
In a separate 2016 study, investigators identified the following as independent prognostic factors for poor long-term survival in patients with head and neck SCC and distant metastasis following initial definitive treatment[28]:
The images show advanced SCC involving nearly all the upper and lower lips as well as the oral commissure and the left cheek in a Thai patient. Top left: frontal view. Top right: worm eye view. Bottom left: right lateral view. Bottom right: left lateral view.
Images courtesy of Burusapat C, Pitiseree A. J Med Case Rep. 2012;6:23. [Open access.] PMID: 22257635, PMCID: PMC3287129.
Epidermal growth factor receptor
Improved knowledge of the molecular mechanisms underlying progression of head and neck malignancies have led to advances in molecular biology and the development of targeted therapeutic agents.
Epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, is overexpressed in 80%-90% of head and neck SCCs.[14,29] Increased expression of EGFR and/or common ligands have been associated with disease recurrence and worse patient survival, including decreased overall and disease-free survival.[14,29] Activation of EGFR-dependent signaling pathways (shown) in head and neck SCCs leads to disease progression through tumor cell proliferation and anti-apoptosis.
Several strategies have been developed to target EGFR, including antibodies that target the extracellular ligand-binding region of EGFR and small-molecule inhibitors of the intracellular tyrosine kinase domain of EGFR (tyrosine kinase inhibitors).[14,29]
Image courtesy of Wikimedia Commons/Eikuch.
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