HEAD AND NECK SQUAMOUS CELL CARCINOMA

SCC is the most common malignancy of the upper aerodigestive tract, and is associated with

approximately 50% overall survival due to its aggressive nature and the tendency for patients to present

with advanced stage. The staging criteria for the common head and neck tumor subsites are available in

the American Joint Commission on Cancer or the National Cancer Comprehensive Network.15,31 Staging

is based on the size and invasiveness of the primary tumor site, the number, size, and location of

metastatic lymph nodes, and the presence or absence of distant metastases. Tables 41-6 to 41-9 list the

TNM staging for the oral cavity, oropharynx, and larynx, which are grouped into an overall stage of I to

IV (Table 41-10). Patients with AJCC stage I/II tumors may be treated with single modality therapy,

radiation, or surgery. Those with stage III/IV will require multimodality treatment. It is of particular

importance that higher-stage patients undergo multidisciplinary evaluation due to combination therapy

and the need for aggressive functional rehabilitation after treatment.

Table 41-6 Oral Cavity Staging

Table 41-7 Oropharynx Staging

ORAL CAVITY

4 The subsites of the oral cavity include the lip, oral tongue, floor of mouth, hard palate, gingival

mucosa and retromolar trigone, and buccal mucosa. Although patients are given the choice between

surgical and nonsurgical treatment in most head and neck cancers, surgery is considered the primary

treatment for oral cancer because of its ease of access and because of the risk of osteoradionecrosis of

the mandible when high-dose radiation or chemoradiation is used in the region. Microvascular

reconstruction is very important to restore the structure and function of the structures of the oral cavity

to preserve speech and swallowing and minimize cosmetic deformity for larger tumors, and may require

bone, soft tissue, or a combination of both.

Table 41-8 Larynx Staging

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Table 41-9 Nodal Staging for Salivary Cancers and Squamous Cell Carcinoma of

Oral Cavity, Oropharynx, Larynx

Site-specific considerations are important oncologically and functionally for oral cavity cancer. Lower

lip carcinoma, which is most common and often due to sun exposure, has a very low incidence of occult

cervical metastases (<15%), and may be observed in stage I/II with clinically negative nodes.31 In

contrast, the upper lip has unilateral drainage, but a higher incidence of nodal involvement.

Reconstruction of the lip may involve primary closure or local advancement for small lesions (<1/3 of

length), and local or free flap reconstruction for larger tumors.32

In oral tongue cancer, depth of invasion is clinically important. Very thin tumors (<2 mm) have a

low likelihood to spread to regional lymphatics, in contrast to thick tumors (>8 to 9 mm). Although a

definitive consensus has not been reached, many surgeons advocate elective neck dissection for patients

with T1 tumors and depth of invasion >4 mm.33 T1–T2 tongue tumors may be resected and closed

primarily or with a skin or acellular dermis graft; larger lesions require microvascular reconstruction

with enough bulk to allow for speech and deglutition. Similarly, small floor of mouth resections may be

closed primarily, and grafts may be used when the floor of mouth musculature is preserved, but

additional tissue is needed for larger tumors to prevent orocutaneous fistula when simultaneous neck

dissection is performed.

STAGING

Table 41-10 AJCC Stage Grouping for Cancers of the Head and Neck (Excluding

Thyroid and Nasopharynx)

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Lesions of the retromolar trigone and buccal mucosa/space present a challenge due to early

involvement of the muscles of mastication. Pterygoid and/or masseter may cause severe trismus,

making preoperative examination and intraoperative exposure difficult. Marginal mandibulectomy

(removal of the inner cortex) may be necessary when the tumor is attached to mandibular periosteum.

Composite resection of a segment of mandible is required when the integrity of the bone is

compromised on preoperative imaging, or when tumor has infiltrated via a tooth root or neural

foramen. Microvascular osteocutaneous reconstruction has become the standard of care for most

segmental defects due to the cosmetic and functional deformity of nonreconstruction (“mandibular

swing”), and because of delayed hardware extrusion that occurs after several years with plating and soft

tissue coverage alone.

NASOPHARYNX

Nasopharyngeal carcinoma (NPC) is an uncommon entity in most of the world, but is endemic to certain

parts of Asia, most notably southern China. Although environmental and dietary factors play a role in

the development of NPC, the most important causal factor is Epstein–Barr virus.34–36 The World Health

Organization subclassifies NPC into three types: keratinizing SCC (I), nonkeratinizing SCC (II), and

undifferentiated carcinoma (III).24 Endemic NPC is 95% type III, which is associated with the best

prognosis, and types I and II are more common in nonendemic areas.

Because the nasopharynx is not easily visualized, and because tumors tend to metastasize early, the

most common presenting symptom is bulky lymphadenopathy. Of note, large lymphadenopathy is less

prognostic in NPC than involvement of the supraclavicular fossa, which is reflected in a different nodal

staging than for other head and neck subsites.15 Other possible complaints at presentation include nasal

obstruction, speech changes, and hearing loss due to involvement of the eustachian tube. Cranial nerve

palsies signify extension into the skull base, suggesting advanced disease.

Biopsy of the nasopharynx or lymph nodes to confirm NPC should be accompanied by imaging with

CT and MRI to evaluate the skull base and infratemporal fossa. The primary treatment for NPC is

nonsurgical, and concurrent chemoradiation has been shown to be superior to radiation alone in

advanced disease.37,38 Surgery is reserved for failure of chemoradiation, and can be successful in

patients with localized disease. In a large series of 312 patients undergoing salvage nasopharyngectomy,

the 5-year overall survival was 62%,39 although the majority of patients required a transfacial approach

with maxillary disarticulation. With the advent of endoscopic techniques, some recurrences may be

salvaged without traditional open approaches via the transnasal or transpterygoid approach, although

control of the internal carotid artery is a concern.40 Similarly, transoral robotic surgery has been

reported for recurrences limited to soft tissue, although division of the soft palate is necessary, and

there are no currently available robotic instruments that are suited to remove bone.41

OROPHARYNX

The oropharynx is comprised of the palatine tonsillar fossae and tonsils, base of tongue, soft palate, and

posterior pharyngeal wall. While the incidence of head and neck SCC of other subsites has decreased

with the prevalence of smokers in the United States, oropharyngeal cancer incidence has risen over the

past two decades. This correlates with our understanding that the human papillomavirus, particularly

subtypes 16 and 18, play a pathogenic role in squamous carcinoma of the oropharynx, and it is now

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believed that HPV is responsible for approximately 80% of oropharyngeal cancer.42 In contrast to the

poor prognosis of HPV-negative carcinoma of the oropharynx, HPV-associated cancer is associated with

a favorable prognosis.43,44

Figure 41-11. Transoral robotic surgery for a tongue base tumor. The retractor (green arrow) retracts the oral tongue. The lateral

cut has been made 1 cm away from the tumor (yellow asterisk); the epiglottis (black arrow) is retracted to visualize the vallecula.

Although small T1–T2 tumors of the tonsils are often amenable to transoral excision,45 radiation and

concurrent chemoradiation have been used since the 1990s to treat less accessible and larger tumors due

to equivalent effectiveness and decreased morbidity and mortality compared to the traditional open

approaches, which involved transcervical, transpharyngeal, or transmandibular resection.46 However,

the rising prevalence of younger HPV-positive patients with favorable prognosis and the advent of

minimally invasive approaches have led to increased interest in surgery as primary treatment, due to

the long-term sequelae of radiation and chemotherapy.

Transoral laser microsurgery (TLM) and transoral robotic surgery have emerged in the past 10 years

as techniques to treat T1–T3 tumors transorally with acceptable oncologic and functional outcomes.47,48

Advanced optics and instrumentation allow for complete tumor resection without requiring morbid open

approaches (Figs. 41-11 and 41-12). Currently two prospective NCI funded trials, ECOG 3311(HPV+ n

= 377) and RTOG 1221 (HPV– n = 144), are underway to determine the role of surgical treatment for

HPV positive and negative oropharyngeal cancer.49

HYPOPHARYNX

The hypopharynx, comprised of the pyriform sinuses, postcricoid mucosa, and posterior pharyngeal wall

below the level of the hyoid, is the area between the oropharynx and cervical esophagus. For the

purposes of this chapter, cervical esophageal cancer will not be discussed. Cancer of the hypopharynx

may present insidiously, with gradually increasing dysphagia, hoarseness due to laryngeal involvement,

or ear pain referred through cranial nerves IX and X via Jacobson and Arnold nerves.

Compared to other subsites, the hypopharynx has a poorer prognosis, with an overall survival of only

30% to 35% in early stage cancer,50 and a rate of distant metastases of up to 60%.51 Because of its

proximity to laryngeal structures, hypopharyngeal cancer is typically treated nonoperatively, as most

tumors would require removal of the larynx. Although induction chemotherapy followed by definitive

radiation may be used in these patients, many institutions prefer concurrent chemoradiation,

extrapolating the improved outcomes of concurrent CRT over sequential treatment in trials of other

subsites. Small hypopharyngeal tumors of the posterior wall or pyriform sinus may be treated with

transoral laser or robotic techniques,52,53 although bilateral neck dissection is required for regional

control. Recurrent hypopharyngeal cancer may require total laryngectomy with partial pharyngectomy,

or laryngopharyngectomy with microvascular reconstruction of the neopharynx.

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Figure 41-12. Resultant defect from TORS resection, demonstrating the lingual artery in situ, which was coagulated later with

bipolar cautery to prevent bleeding.

LARYNX

Tobacco and alcohol have a dose-dependent, synergistic carcinogenic effect on the epithelium of the

larynx. The glottis, or true vocal cords, is the most common subsite involved, followed by the

supraglottis (tip of the epiglottis to the laryngeal ventricle), and subglottis (1 cm below ventricle to the

inferior border of the cricoid cartilage). In contrast to the respiratory epithelium of the rest of the upper

aerodigestive tract, the glottis is comprised of stratified squamous nonkeratinizing epithelium overlying

a complex lamina propria over the thyroarytenoid ligament and muscle. Due to the fibroelastic support

of the conus elasticus and quadrangular membrane, early glottic tumors have a very low propensity for

spread to regional lymph nodes, in contrast to the supraglottis and subglottis.

5 Early-stage carcinoma of the glottis (T1–T2) can be treated with single modality radiation or

surgery, with approximately 90% cure for T1 and 75% for T2; early recognition and diagnosis at this

stage therefore is key. Surgical treatment is performed via transoral resection, often using the CO2

laser, which has no statistically significant difference in overall or disease-free survival or local control

compared to radiation, although laryngeal preservation rates appear to be higher in the surgical group

based on retrospective studies.54–56 Transoral resection of early glottic and supraglottic cancer has the

advantage of requiring only one treatment, compared to the 6 to 7 weeks of radiation needed.

However, supraglottic carcinoma has a high incidence of occult nodal metastasis, as well as bilateral

drainage, and therefore planned bilateral level 2–4 neck dissection is recommended for patients who

undergo surgery for the primary tumor.

For advanced laryngeal cancer (T3–T4), either surgery followed by radiation or concurrent

chemoradiation may be offered, based on two randomized clinical trials. The so-called “VA Trial”

demonstrated equivalent survival between surgery and radiation versus induction chemotherapy

followed by radiation, with 64% laryngeal preservation in the nonsurgical arm.57 This was followed by

the RTOG 91–11 trial, which demonstrated the superiority of concurrent chemoradiation compared to

radiation alone or after induction chemotherapy for laryngectomy-free survival and local control.58

However, the 10-year follow-up to this study did not demonstrate an advantage of concurrent CRT

versus induction chemotherapy and radiation in overall survival, local control, or overall laryngeal

preservation.59

For advanced stage laryngeal cancer, surgery generally involves total laryngectomy with bilateral

lymphadenectomy, with local tissue or free tissue transfer as needed for pharyngeal reconstruction. This

procedure functionally separates the airway from the digestive tract, but allows for effective verbal

communication via esophageal speech, tracheoesophageal puncture with prosthesis, or electrolarynx.

Open partial laryngeal surgeries, including supraglottic or supracricoid partial laryngectomy, may be

used in selected cases, but have prolonged recovery of swallowing and airway protection.

Additional factors must be considered in choosing a treatment modality for patients with advanced

stage laryngeal cancer. Radiation is less effective in cartilage and bone, and therefore thought to be

inferior to surgery in T4 laryngeal cancer.60 Additionally, patients who present with extensive

paraglottic spread and vocal cord fixation will not regain function of the larynx with treatment, and are

likely to remain tracheostomy-dependent if tracheotomy is performed prior to nonsurgical treatment.61

Similarly, patients with poor pretreatment swallowing are likely to worsen, and may

milarly, patients with poor pretreatment swallowing are likely to worsen, and may become

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