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20 Laryngeal Squamous Cell Carcinoma
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• T3—Tumor limited to larynx with vocal cord xation and/or invades postcricoid
area, pre-epiglottic tissue, paraglottic space, and/or inner cortex of thyroid
cartilage
• T4a—Tumor invades through thyroid cartilage and/or invades tissue beyond the
larynx (e.g., trachea, soft tissue of neck including deep extrinsic muscle of the
tongue, strap muscles, thyroid, esophagus)
• T4b—Tumor invades prevertebral space, encases carotid artery, or invades medi-
astinal structures
Primary tumor (T): Glottis
• TX—Primary tumor cannot be assessed
• T0—No evidence of primary tumor
• Tis—Carcinoma in situ
• T1—Tumor limited to the vocal cord(s) with normal mobility (may involve ante-
rior/posterior commissure)
• T1a—Tumor limited to one vocal cord
• T1b—Tumor involves both vocal cords
• T2—Tumor extends to supraglottis and/or subglottis, and/or with impaired
mobility
• T3—Tumor limited to larynx with vocal cord xation and/or invades paraglottic
space, and/or inner cortex of thyroid cartilage
• T4a—Tumor invades through thyroid cartilage and/or invades tissues
beyond larynx
• T4b—Tumor invades prevertebral space, encases carotid artery, or invades medi-
astinal structures
Primary tumor (T): Subglottis
• TX—Primary tumor cannot be assessed
• T0—No evidence of primary tumor
• Tis—Carcinoma in situ
• T1—Tumor limited to the subglottis
• T2—Tumor extends to the vocal cord(s) with normal or impaired mobility
• T3—Tumor limited to larynx with vocal cord xation
• T4a—Tumor invades the cricoid or thyroid cartilage and/or invades tissues
beyond the larynx
• T4b—Tumor invades prevertebral space, encases carotid artery, or invades medi-
astinal structures
Regional lymph nodes (N)
• N—Regional lymph nodes cannot be assessed
• N0—No evidence of regional lymph node metastasis
• N1—Metastasis to a single ipsilateral lymph node ≤3cm in greatest dimension
• N2a—Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest
dimension
• N2b—Metastasis in multiple ipsilateral lymph nodes ≤6cm in greatest dimension
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• N2c—Metastasis in bilateral or contralateral lymph nodes ≤6 cm in greatest
dimension
• N3—Metastasis in a lymph node >6cm in greatest dimension
Distant metastasis (M)
• Mx—Distant metastasis cannot be assessed
• M0—No distant metastasis
• M1—Distant metastasis
American Joint Committee Staging
• Stage 0—Tis, N0, M0
• Stage I—T1, N0, M0
• Stage II—T2, N0, M0
• Stage III
– T3, N1, M0
– T3, N0, M0
– T1, N1, M0
– T2, N1, M0
– T3, N1, M0
• Stage IVA
– T4a, N0, M0
– T4a, N1, M0
– T1, N2, M0
– T2, N2, M0
– T3, N2, M0
– T4a, N2, M0
A. K. Badhey et al.
• Stage IVB
– Any T, N3, M0
– T4b, any N, M0
• Stage IVC
– Any T, any N, M1
Management
• Goals of treatment are cure and laryngeal preservation.
• Premalignant lesions.
– Hyperplasia
– Keratosis
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– Dysplasia
Mild
Moderate
Severe
– Carcinoma in situ.
– Treated with microsurgical excision or RT.
Radiation therapy
• Apx 90% local control rate.
• Preferred for diffuse or recurrent lesions.
• Voice outcomes not signicantly different from surgical excision.
Microsurgical excision.
• Apx 80% local control rate.
• May need to be repeated multiple times.
Vocal fold stripping.
• Apx 75% local control rate.
• Higher risk of vocal fold scarring, adverse voice outcomes.
• Supraglottic SCCA
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– Early primary (T1, T2, select T3).
Open supraglottic laryngectomy (OSL)
• Resection of upper half of thyroid cartilage, false vocal cords, epiglottis, pre-epiglottic space, aryepiglottic folds.
• Indications
– T1, T2, select T3 with pre-epiglottic involvement but without glottic
involvement
• Contraindications
– Poor pulmonary reserve or medical condition.
– Vocal cord xation
– Thyroid or cricoid cartilage invasion.
– Tumor in deep muscles of tongue or within 1cm of circumvallate
papilla.
• Local control ~90%.
Transoral laser microsurgery
• Similar indications and contraindications as OSL.
• Comparable oncologic outcomes.
• Less morbidity, shorter hospital stays, less frequent need for temporary
tracheostomy, equivalent voice outcomes.
• May be limited by exposure.
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Adjuvant RT recommended for positive margins, lymphovascular or perineural invasion, extracapsular spread, or N2+ disease.
Primary RT
• Slightly lower initial local control rate, but surgical salvage gives an
ultimate local control rate comparable to primary surgical treatment.
• Useful in patients with contraindications to surgical procedure, poor
pulmonary function.
Total laryngectomy for salvage.
– Advanced primary
Concurrent chemotherapy and radiation (CCRT)
• Department of Veterans Affairs (VA) Laryngeal Cancer Study.
– Induction chemotherapy with RT had equivalent survival to total lar-
– 64% rate of laryngeal preservation in nonsurgical arm.
– Combination of chemotherapy acts as a radiosensitizing agent
– CRT comes with a host of long-term toxicities including dysphagia,
• RTOG 91-11
A. K. Badhey et al.
yngectomy with RT.
weight loss, gastrostomy, and tracheostomy dependence
– Examined the survival of patients undergoing three forms of nonsur-
gical treatment; CCRT, induction chemotherapy followed by radiation, and radiation alone.
– CCRT higher rates of locoregional control and laryngeal preserva-
tion compared to induction chemotherapy, then RT, and RT alone.
– Increased acute toxicity with CCRT.
Total laryngectomy with adjuvant RT
• Primary treatment in patients not amenable to supracricoid partial laryngectomy (SCPL) or concurrent chemoradiotherapy.
– Generally patients with signicant cartilage destruction or extrala-
ryngeal spread.
• Used for salvage in recurrent disease, or in cases of nonfunctional larynx after CCRT.
– Neck treated surgically with a bilateral selective II–IV dissection in case of
N0 or N1 neck, comprehensive level I–V in case of N2 or N3 disease.
• Glottic SCCA
– Early primary (T1, T2)
All treatment methods generally have very high local control, laryngeal
preservation, and disease-free survival.
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Elective treatment of the N0 neck is not indicated.
Radiotherapy
• T2 with impaired mobility signicantly lower rates of local control
(76.1% vs. 51.1%) and 5-year survival (86.8% vs. 75.2%).
Transoral laser surgery
• Anterior commissure involvement increases recurrence rate.
• Similar voice outcomes with RT for T1 lesions.
Vertical partial laryngectomy (VPL)
• Removal of ipsilateral false and true cord.
• Superior rates of local control for patients with T2 lesions.
• Relatively poor voice outcomes compared to RT, laser cordectomy.
• SCPL more extensive with poorer voice quality, but improved local
control when anterior commissure is involved.
– Advanced primary
Concurrent chemoradiotherapy and total laryngectomy with postoperative
RT (see discussion of RTOG and VA trials above).
Total laryngectomy indicated for T4a tumors with extensive cartilage
destruction and as surgical salvage after CCRT.
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• Subglottic SCCA
– Treatment guidelines limited by rarity of disease.
Early-stage disease amenable to treatment with primary radiotherapy.
Advanced disease treated with laryngectomy, neck dissection, adjuvant
radiotherapy.
Generally grim prognosis (25% 3-year DFS in one series) given propensity
to present in advanced stage and with distant metastases.
Other Laryngeal Malignancies
• Spindle cell carcinoma
– Has both squamous and spindle cell elements.
Some debate about biological behavior, but most accepted theory is that of
an epithelial origin with metaplastic transformation.
– Tobacco and alcohol most common etiologic factors.
– Male predominance.
– Most commonly glottic.
Supraglottic and subglottic tumors associated with lower survival and
more regional metastases, similar to SCCA.
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A. K. Badhey et al.
– Commonly polypoid and exophytic.
– Treatment and prognosis similar to SCCA.
Traditionally treated primarily surgically, data for treatment with primary
radiation very limited but case reports support its possible use in earlystage lesions.
• Chondrosarcoma
– Uncommon laryngeal malignancy, less than 1%.
– Male predominance.
– Typically arise in cricoid cartilage.
– Most commonly low grade, with good prognosis.
5-year survival 90%.
High-grade tumors, though uncommon, have worse prognosis and higher
tendency to metastasize.
– Treated with partial or total cricoid resection.
High-grade tumors may require total laryngectomy.
– Radiation experience is very limited, but may be an option if conservation
laryngeal surgery not feasible or as salvage prior to total laryngectomy.
Further Reading
1. Armstrong WB, Vokes DE, Maisel RH.Malignant tumors of the larynx. In: Flint PW, Haughey
BH, Lund VJ, Niparko JK, Nager GT, Richardson MA, Robbins KT, Thomas JR, editors.
Cummings otolaryngology-head & neck surgery. 5th ed. Philadelphia, PA: Mosby; 2010.
p.1482–511.
2. Bron LP, Soldati D, Monod ML, etal. Horizontal partial laryngectomy for supraglottic squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2005;262:302–6.
3. de Jong RJB, van Lent S, Hogendoorn PC.Chondroma and chondrosarcoma of the larynx.
Curr Opin Otolaryngol Head Neck Surg. 2004;12:98–105.
4. de Zinis LOR, Nicolai P, Tomenzoli D, etal. The distribution of lymph node metastases in
supraglottic squamous cell carcinoma: therapeutic implications. Head Neck. 2002;24:913–20.
5. El-Serag HB, Hepworth EJ, Lee P, etal. Gastroesophageal reux disease is a risk factor for
laryngeal and pharyngeal cancer. Am J Gastroenterol. 2001;96:2013–8.
6. Brazilian Head and Neck Cancer Study Group. End results of a prospective trial on elective
lateral neck dissection vs type III modied radical neck dissection in the management of supraglottic and transglottic carcinomas. Head Neck. 1999;21:694–702.
7. Ferlito A, Rinaldo A. The pathology and management of subglottic cancer. Eur Arch
Otorhinolaryngol. 2000;257:168–73.
8. Forastiere AA, Goepfert H, Maor M, etal. Concurrent chemotherapy and radiotherapy for
organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–8.
9. Garas J, McGuirt WF Sr. Squamous cell carcinoma of the subglottis. Am J Otolaryngol.
2006;27:1–4.
10. Greene F, Page D, Fleming I, et al. AJCC cancer staging manual. 6th ed. NewYork, NY:
Springer; 2002.
20 Laryngeal Squamous Cell Carcinoma
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11. Gripp S, Pape H, Schmitt G.Chondrosarcoma of the larynx: the role of radiotherapy revisited—a case report and review of the literature. Cancer. 1998;82:108–15.
12. Harrison DF.The pathology and management of subglottic cancer. Ann Otol Rhinol Laryngol.
1971;80:6–12.
13. Harwood AR, DeBoer G.Prognostic factors in T2 glottic cancer. Cancer. 1980;45:991–5.
14. Hoffman HT, Porter K, Karnell LH, etal. Laryngeal cancer in the United States: changes in
demographics, patterns of care, and survival. Laryngoscope. 2006;116:1–13.
15. The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy
plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991;324:1685–90.
16. Jemal A, Siegel R, Ward E, etal. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.
17. Laccourreye O, Muscatello L, Laccourreye L, etal. Supracricoid partial laryngectomy with
cricohyoidoepiglottopexy for “early” glottic carcinoma classied as T1-T2N0 invading the
anterior commissure. Am J Otolaryngol. 1997;18:385–90.
18. Mendenhall WM, Parsons JT, Mancuso AA, etal. Radiotherapy for squamous cell carcinoma
of the supraglottic larynx: an alternative to surgery. Head Neck. 1996;18:24–35.
19. Mendenhall WM, Werning JW, Hinerman RW, Amdur RJ, Villaret DB.Management of T1–T2
glottic carcinomas. Cancer. 2004;100:1786–92.
20. Menvielle G, Luce D, Goldberg P, et al. Smoking, alcohol drinking and cancer risk for various sites of the larynx and hypopharynx: a case–control study in France. Eur J Cancer Prev.
2004;13:165–72.
21. Olsen KD, Lewis JE, Suman VJ.Spindle cell carcinoma of the larynx and hypopharynx.
Otolaryngol Head Neck Surg. 1997;116:47–52.
22. Peretti G, Piazza C, Cattaneo A, etal. Comparison of functional outcomes after endoscopic
versus open-neck supraglottic laryngectomies. Ann Otol Rhinol Laryngol. 2006;115:827–32.
23. Sadri M, McMahon J, Parker A.Management of laryngeal dysplasia: a review. Eur Arch
Otorhinolaryngol. 2006;263:843–52.
24. Thompson LD, Wieneke JA, Miettinen M, etal. Spindle cell (sarcomatoid) carcinomas of the
larynx: a clinicopathologic study of 187 cases. Am J Surg Pathol. 2002;26:153–70.
25. Tufano RP. Organ preservation surgery for laryngeal cancer. Otolaryngol Clin North Am.
2002;35:1067–80.
26. Waldfahrer F, Hauptmann B, Iro H.Lymph node metastasis of glottic laryngeal carcinoma.
Laryngorhinootologie. 2005;84:96–100.
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Chapter 21
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Oral Cavity andOropharyngeal Squamous
Cell Carcinoma
AmeyaA.Jategaonkar andMohemmedKhan
Pearls
• Oral cavity cancer is associated with tobacco and alcohol whose concurrent use
synergistically increases the risk of developing cancer
• Bone invasion of the mandible or the maxilla represents advanced T stage and is
associated with a poorer prognosis
• Cervical metastasis is the most inuential prognostic factor and confers a 50%
decrease in survival.
• Tumors >5mm thickness have higher (20%>) risk of cervical metastasis, and as
such, elective neck dissection should be performed in the N0 neck with advanced
depth of invasion
• HPV(+) oropharyngeal cancer represents a unique entity when compared to
HPV(−) cancers with signicantly better prognoses
• HPV-related OP SCCA may initially present as a painless neck mass
• Given the improved prognosis, only patients with distant metastases are consid-
ered as stage IV for HPV-related OP SCCA
A. A. Jategaonkar (*)
Department of Otolaryngology and Skull Base Surgery, Barrow Neurological Institute,
Phoenix, AZ, USA
M. Khan
Department of Otolaryngology - Head and Neck Surgery, Icahn School of Medicine at the
Mount Sinai Hospital, New York, NY, USA
e-mail: mohemmed.khan@mountsinai.org
© Springer Nature Switzerland AG 2023
F. Y. Lin, Z. M. Patel (eds.), ENT Board Prep,
https://doi.org/10.1007/978-3-031-26048-3_21
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A. A. Jategaonkar and M. Khan
Oral Cavity Squamous Cell Carcinoma
Anatomy
• The oral cavity begins at the junction of the skin and vermillion of the lip anteri-
orly. Posteriorly, the oral cavity transitions into the oropharynx at the junction of
the hard and soft palate superiorly and at the circumvallate papillae inferiorly. The
oral cavity is broken down into 7 subsites. Cancers of the oral cavity metastasize
to the lymphatics of the neck in typically predictable patterns to levels I, II, and III.
Oral Cavity Subsites
• Lips (gingiva to the vermillion-skin junction)
• Buccal mucosa
• Oral tongue
• Floor of mouth
• Hard palate
• Alveolar ridge
• Retromolar trigone
Epidemiology/Pathogenesis
• 95% of oral cavity cancers are squamous cell carcinomas (SCCA). Minor sali-
vary gland cancers, mucosal melanomas, lymphomas, and sarcomas make up the
other oral cavity malignancies.
• Oral cavity SCCA is associated with eld cancerization and patients are at a
signicant risk of developing a second primary malignancy (e.g., lung or esophageal cancers).
Risk Factors
• Tobacco use (smoking or chewing)
• Alcohol (this risk is synergistic with concurrent tobacco use)
• Betel nut (commonly used in certain parts of Asia)
• Immunosuppression
• Sun exposure (this is why the lower lip is at greatest risk)
• Inammatory disorders of the oral cavity (e.g., lichen planus or chronic poor oral
care/hygiene)
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Clinical Presentation
• Patients will typically present with complaints of pain, odynophagia, or dyspha-
gia. Other complaints include pain with certain foods such as acidic foods, persistent oral sores, or mucosal irregularities. Loose dentition may also be noted.
Paresthesias of the lip, trismus, or pathologic mandibular fractures may be presenting signs of locally advanced disease. A neck mass may also be the presenting symptom.
• Patients may also present with premalignant lesions such as leukoplakia (white
lesion) or erythroplakia (red, higher risk lesion) that need to be monitored/
biopsied.
Work-Up
• Physical Exam:
– All patients with suspected oral cavity cancer should undergo a thorough head
and neck exam including the tumor (assessment for size, depth, mobile vs.
adherent to mandible), cranial nerve exam, cervical nodal exam, and evalua-
tion of the airway.
– Biopsy of lesion
– Consider FNA if any neck masses
• Imaging:
– Computed tomography (CT) with contrast is the preferred imaging modality
to assess local/regional disease. Magnetic resonance imaging (MRI) may be
useful in characterizing soft tissue involvement and to assess for perineural
invasion (PNI). Dental radiographs such as panoramic radiographs may better
evaluate bony disease. Positron emission tomography (PET) or PET/CT can
be used to evaluate for distant metastasis and screen for neck metastases.
Staging
Staging is based upon the AJCC eighth Edition TNM staging system.
Primary Tumor (T Stage)
• Tx: Primary tumor cannot be assessed
• Tis: Carcinoma in situ
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