Oropharyngeal Neoplasms

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Oropharyngeal Neoplasms

Head and Neck Surgery
Author Credentials 

Gregory Hartig, MD
Professor of Otolaryngology 
Department of Surgery University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin

David M. Neskey, MD
Assistant Professor 
Department of otolaryngology head and neck surgery
Medical university of South Carolina
Charleston, South Carolina

A. Daniel Pinheiro, MD, PhD
Clinical Assistant Professor of Surgery and Otolaryngology 
University of Missouri – Columbia
Director, Mercy Head and Neck Program
Springfield, Missouri

Module Summary

Oropharyngeal neoplasms (OPNs) can include a broad differential of benign and malignant processes. Although the differential of OPN is broad, one must first differentiate a neoplastic from non-neoplastic process. This is best accomplished with tissue diagnosis.  HPV positive oropharygneal squamous cell carcinoma (OPSCC) is the most significant neoplastic entity in this anatomic area, given its increasing incidence. Therefore, this module is heavily weighted toward improving understanding of this disease while also reminding the reader of other neoplastic processes which can be found in the oropharynx.
HPV-related OPSCC is the most common head and neck malignancy and its incidence has been increasing in the past 2 decades. Surgical and non-surgical options exist for management of these cancers and both have specific challenges and limitations. Long-term preservation of swallowing function needs to be the goal of therapy since most patients will achieve disease free status.
 

Module Learning Objectives 
  1. Explain surgical and non-surgical treatment options for oropharynx neoplasms.
  2. Compare and contrast advantages and limitations of surgical and non-surgical treatment options for oropharynx cancer.
  3. Recognize how treatment of oropharynx tumors can affect swallowing function.
  4. Describe factors related to development of oropharynx cancer and primary prevention of HPV-positive and HPV-negative cancers.
  5. Cite the relevant anatomy and limitations or transoral approaches to the oropharynx.

Embryology

Learning Objectives 
  1. Describe branchial cleft anomalies and understand how second and third branchial cleft cysts are included in the differential diagnosis of metastatic carcinoma from oropharynx primary.
  2. Explain the embryology of the base of tongue and foramen cecum and how a lingual thyroid should be included in the differential diagnosis of oropharynx neoplasms.
  3. Describe how the innervation of the base of tongue differs the innervation of the anterior 2/3 of the tongue.
References 
  1. Pansky, B. Review of Medical Embryology. Embryome Sciences, Inc 1301 Harbor Bay Parkway, Alameda, CA, 94502. 
  2. Bishop JA, Westra WH. Ciliated HPV-related Carcinoma: A Well-differentiated Form of Head and Neck Carcinoma That Can Be Mistaken for a Benign Cyst. Am J Surg Pathol. 2015 Nov;39(11):1591-5. 
  3. Bradley PT, Bradley PJ. Branchial cleft cyst carcinoma: fact or fiction? Curr Opin Otolaryngol Head Neck Surg. 2013 Apr;21(2):118-23.
  4. Devaney KO, Rinaldo A, Ferlito A, Silver CE, Fagan JJ, Bradley PJ, Suárez C. Squamous carcinoma arising in a branchial cleft cyst: have you ever treated one? Will you? J Laryngol Otol. 2008 Jun;122(6):547-50. 
  5. Noussios G, Anagnostis P, Goulis DG, Lappas D, Natsis K. Ectopic thyroid tissue: anatomical, clinical, and surgical implications of a rare entity. Eur J Endocrinol. 2011 Sep;165(3):375-82.
  6. Prisman E, Patsias A, Genden EM. Transoral robotic excision of ectopic lingual thyroid: Case series and literature review. Head Neck. 2015 Aug;37(8):E88-91. 

Anatomy

Learning Objectives 
  1. Describe the structures that make up the oropharynx and understand the boundaries between the oropharynx, oral cavity, nasopharynx and hypopharynx.
  2. Explain the transoral medial to lateral anatomy of the oropharynx and its implications for transoral surgical approaches.
  3. Recognize the implications of aberrant course of carotid artery have for surgical approaches to the oropharynx.
  4. Describe how cranial nerves 9, 10 and 12 contribute to innervation of oropharynx structures.
References 
  1. Lim CM, Mehta V, Chai R, Pinheiro CN, Rath T, Snyderman C, Duvvuri U. Transoral anatomy of the tonsillar fossa and lateral pharyngeal wall: anatomic dissection with radiographic and clinical correlation. Laryngoscope. 2013 Dec;123(12):3021-5.
  2. Gun R, Durmus K, Kucur C, Carrau RL, Ozer E. Transoral Surgical Anatomy and Clinical Considerations of Lateral Oropharyngeal Wall, Parapharyngeal Space, and Tongue Base. Otolaryngol Head Neck Surg. 2016 Mar;154(3):480-5. 
  3. Gupta A, Shah AD,  Zhang Z, Phillips CD, Young RJ. Variability in the Position of the Retropharyngeal Internal Carotid Artery: A Potential Surgical Hazard. Laryngoscope. 2013 Feb;123(2):401–403. 
  4. Muñoz A., De Vergas J, Crespo J. Imaging and Clinical Findings in Patients with Aberrant Course of the Cervical Internal Carotid Arteries. Open Neuroimag J. 2010;4:174-181.

Pathogenesis

Learning Objectives 
  1. Describe the role of HPV in pathogenesis of oropharynx squamous cell carcinoma.
  2. Explain role of HPV vaccine in primary prevention of oropharynx cancer.
  3. Describe the pathogenesis of dysphagia secondary to surgical and non-surgical management of oropharyngeal neoplasms. 
  4. Explain the frequency, severity and recovery of dysphagia after TORS for OPSCCa. 
References 
  1. Tulay P, Serakinci N. The role of human papillomaviruses in cancer progression. J Cancer Metasta Treat. 2016;2:201-13. 
  2. Miller DL, Puricelli MD, Stack MS. Virology and Molecular Pathogenesis of Human Papillomavirus (HPV)-Associated Oropharyngeal Squamous Cell Carcinoma. Biochem J. 2012 Apr 15;443(2):339-53.
  3. Human Papillomavirus (HPV) Vaccines. National Cancer Institute. Accessed on May 15, 2018. 
  4. Kao SS, Peters MD, Krishnan SG, Ooi EH. Swallowing outcomes following primary surgical resection and primary free flap reconstruction for oral and oropharyngeal squamous cell carcinomas: A systematic review. Laryngoscope. 2016 Jul;126(7):1572-80.
  5. Albergotti WG, Jordan J, Anthony K, Abberbock S, Wasserman-Wincko T, Kim S, Ferris RL, Duvvuri U. A prospective evaluation of short-term dysphagia after transoral robotic surgery for squamous cell carcinoma of the oropharynx. Cancer. 2017 Aug 15;123(16):3132-3140. 

Basic Science

Learning Objectives 
  1. Recognize mechanisms of tobacco- and HPV-mediated carcinogenesis in head and neck cancer.
  2. Describe role of checkpoint inhibitors in carcinogenesis.
  3. Cite basic principles of antineoplastic molecular targeting. 
References 
  1. Garrett MD, Collins I. Anticancer therapy with checkpoint inhibitors: what, where and when? Trends Pharmacol Sci. 2011 May;32(5):308-16.
  2. Azoury SC, Gilmore RC, Shukla V. Molecularly targeted agents and immunotherapy for the treatment of head and neck squamous cell cancer (HNSCC). Discov Med. 2016 Jun;21(118):507-16.
  3. Faraji F, Zaidi M, Fakhry C, Gaykalova DA. Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer. Microbes Infect. 2017 Sep - Oct;19(9-10):464-475. 
  4. Jethwa AR, Khariwala SS. Tobacco-related carcinogenesis in head and neck cancer. Cancer Metastasis Rev. 2017 Sep;36(3):411-423. 

Incidence

Learning Objectives 
  1. Describe rising incidence of oropharynx HPV-related oropharynx cancer.
  2. Compare and contrast changing incidence for HPV-positive and HPV-negative squamous cell carcinoma of the oropharynx. 
References 
  1. Chaturvedi AK1, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301.
  2. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009 Apr-May;45(4-5):309-16.

Genetics

Learning Objectives 
  1. Recognize the ways in which the HPV virus interacts with cells in order to replicate and incorporate into the host DNA.
References 
  1. Spriggs CC, Laimins LA. Human Papillomavirus and the DNA Damage Response: Exploiting Host Repair Pathways for Viral Replication. Viruses. 2017 Aug 18;9(8). 
  2. Anacker DC, Moody CA. Modulation of the DNA damage response during the life cycle of human papillomaviruses. Virus Res. 2017 Mar 2;231:41-49. 
  3. Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009 Oct 22;461(7267):1071-8. 

Patient Evaluation

Learning Objectives 
  1. List the factors that can impact timely evaluation and diagnosis for persons with OPNs.    
  2. Review pertinent questioning related to symptoms seen with oropharygneal neoplasms.      
  3. Explain the differences in presentation between persons with HPV+ and HPV- OPSCC.
  4. Given the frequency of associated cervical adenopathy, review AAOHNS  recommendations regarding the evaluation of a neck mass.    
  5. Review new AJCC 8th edition staging changes for HPV-associated oropharyngeal carcinomas.
References 
  1. Gilde J, Song B, Masroor F, Darbinian JA, Ritterman Weintraub ML, Salazar J, Yang E, Gurushanthaiah D, Wang KH. The diagnostic pathway of oropharyngeal squamous cell carcinoma in a large U.S. healthcare system. Laryngoscope. 2017 Dec 15. 
  2. Pynnonen MA, Gillespie MB, Roman B, Rosenfeld RM, Tunkel DE, Bontempo L, Brook I, Chick DA, Colandrea M, Finestone SA, Fowler JC, Griffith CC, Henson Z, Levine C, Mehta V, Salama A, Scharpf J, Shatzkes DR, Stern WB, Youngerman JS, Corrigan MD. Clinical Practice Guideline: Evaluation of the Neck Mass in Adults. Otolaryngol Head Neck Surg. 2017 Sep;157(2_suppl):S1-S30.
  3. Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017 Mar;67(2):122-137.

Measurement of Functional Status

Learning Objectives 
  1. Describe normal and abnormal oropharyngeal swallowing physiology.
  2. Distinguish between a Modified Barium Swallow and a Barium Esophagram.
  3. Cite the principles used for Functional Endoscopic Evaluation of Swallow (FEES).
     
References 
  1. Sasegbon A, Hamdy S. The anatomy and physiology of normal and abnormal swallowing in oropharyngeal dysphagia. Neurogastroenterol Motil. 2017 Nov;29(11).

Imaging

Learning Objectives 
  1. Review the indications for, advantages and disadvantages of CT, MRI and FDG-PET imaging in the evaluation of oropharygeal neoplasms and HPV + OPSCC in particular.
  2. Recognize the importance of lateral retropharyngeal lymph node evaluation in HPV positive OPSCC.
References 
  1. Wang SJ. Surveillance radiologic imaging after treatment of oropharyngeal cancer: a review. World J Surg Oncol. 2015 Mar 7;13:94. 
  2. Baxter M, Chan JY, Mydlarz WK, Labruzzo SV, Kiess A, Ha PK, Aygun N, Agrawal N. Retropharyngeal lymph node involvement in human papillomavirus-associated oropharyngeal squamous cell carcinoma. Laryngoscope. 2015 Nov;125(11):2503-8.

Pathology

Learning Objectives 
  1. Cite the range of distinct neoplastic entities within the oropharynx including benign and malignant salivary gland tumors, epithelial malignancies (including squamous cell carcinoma and melanoma), lymphomas, vascular malformations, neurogenic tumors and lingual thyroid.
  2. Recognize the importance of obtaining a histologic diagnosis of any pharyngeal neoplasm before proceeding with therapy.
  3. Describe the differences between p16 IHC, and HPV PCR or ISH.
  4. Obtain awareness of newly described salivary gland neoplasms.
References 
  1. Qin Y, Lu L, Lu Y, Yang K. Hodgkin lymphoma involving the tonsil misdiagnosed as tonsillar carcinoma: A case report and review of the literature. Medicine (Baltimore). 2018 Feb;97(7):e9761.
  2. Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, Moncur JT, Rocco JW, Schwartz MR, Seethala RR, Thomas NE, Westra WH, Faquin WC. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists. Arch Pathol Lab Med. 2018 May;142(5):559-597.
  3. Skalova A, Michal M, Simpson RH. Newly described salivary gland tumors. Mod Pathol. 2017 Aug;41(8):e33-e47.

Treatment

Learning Objectives 
  1. Explain the appropriate treatment options for the following categories of oropharyngeal neoplasms:
    • Salivary gland malignancies of the pharynx
    • HPV + OPSCC
    • HPV – OPSCC, and HPV+ OPSCC in smokers
  2. Review NCCN guidelines for oropharygneal carcinomas
  3. Appreciate recent trial results regarding HPV associated OPSCC
  4. Describe the neck levels at risk for nodal metastases in OPSCC and the appropriate type of neck dissection for different clinical scenarios.
  5. Recognize risk of retropharyngeal node metastases in OPSCC and appropriate management.
References 
  1. Wang X, Luo Y, Li M, Yan H, Sun M, Fan T. Management of salivary gland carcinomas - a review. Oncotarget. 2017 Jan 17;8(3):3946-3956. 
  2. Stock GT, Bonadio RRCC, de Castro G Junior. De-escalation treatment of human papillomavirus positive oropharyngeal squamous cell carcinoma: an evidence-based review for the locally advanced disease. Curr Opin Oncol. 2018 May;30(3):146-151.
  3. Samuels SE, Eisbruch A, Beitler JJ, Corry J, Bradford CR, Saba NF, van den Brekel MW, Smee R, Strojan P, Suárez C, Mendenhall WM, Takes RP, Rodrigo JP, Haigentz M Jr, Rapidis AD, Rinaldo A, Ferlito A. Management of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we? Eur Arch Otorhinolaryngol. 2016 Oct; 273(10):2877-94.
  4. Moore EJ, Ebrahimi A, Price DL, Olsen KD. Retropharyngeal lymph node dissection in oropharyngeal cancer treated with transoral robotic surgery. Laryngoscope. 2013 Jul;123(7):1676-81. 
  5. Lim YC, Koo BS, Lee JS, Lim JY, Choi EC. Distributions of cervical lymph node metastases in oropharyngeal carcinoma: therapeutic implications for the N0 neck. Laryngoscope. 2006;116(7):1148–52.
  6. Iyer NG, Dogan S, Palmer F, Rahmati R, Nixon IJ, Lee N, et al. Detailed analysis of clinicopathologic factors demonstrate distinct difference in outcome and prognostic factors between surgically treated HPV-positive and negative oropharyngeal cancer. Ann Surg Oncol. 2015;22(13):4411–21.
  7. Gross et al. Level IIB Lymph Node Metastasis in Oropharyngeal Squamous Cell Carcinoma. Laryngoscope.123:2700–2705.
  8. Chung et al. Pattern of cervical lymph node metastasis in tonsil cancer: Predictive factor analysis of contralateral and retropharyngeal lymph node metastasis. Oral Oncology. 2011 Aug;47(8):758-62.

Medical Therapies

Learning Objectives 
  1. Describe role of HPV in oropharynx cancer and understand.
    • Risk factors for HPV related cancer.
    • Immunization for HPV.
    • Behaviors that are likely to transmit HPV
  2. Describe use of radiotherapy for treatment of oropharyngeal neoplasms.
  3. Explain techniques and principles of IMRT as they apply to treatment of oropharynx cancer.
  4. Review acute and long-term toxicity of radiotherapy in the treatment of oropharynx cancer.
References 
  1. Fuertes MA, Castilla J,  Alonso C, Prez JM. Cisplatin Biochemical Mechanism of Action: From Cytotoxicity to Induction of Cell Death Through Interconnections Between Apoptotic and Necrotic Pathways. In Current Medicinal Chemistry. Vol 10. 2003:257-266.
  2. Mirghani H, Jung AC, Fakhry C. Primary, secondary and tertiary prevention of human papillomavirus-driven head and neck cancers. Eur J Cancer. 2017 Jun;78:105-115. 
  3. Semrau R. The Role of Radiotherapy in the Definitive and Postoperative Treatment of Advanced Head and Neck Cancer. Oncol Res Treat. 2017;40(6):347-352. 
  4. Chao KS, Ozyigit G, Blanco AI, Thorstad WL, Deasy JO, Haughey BH, Spector GJ, Sessions DG. Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume. Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):43-50.
  5. Chera BS, Fried D, Price A, Amdur RJ, Mendenhall W, Lu C, Das S, Sheets N, Marks L, Mavroidis P. Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1022-1027. 
  6. Levendag PC, Teguh DN, Voet P, van der Est H, Noever I, de Kruijf WJ, Kolkman-Deurloo IK, Prevost JB, Poll J, Schmitz PI, Heijmen BJ. Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship. Radiother Oncol. 2007 Oct;85(1):64-73. 
  7. Cartmill B, Cornwell P, Ward E, Davidson W, Nund R, Bettington C, Rahbari RM, Poulsen M, Porceddu S. Emerging understanding of dosimetric factors impacting on dysphagia and nutrition following radiotherapy for oropharyngeal cancer. Head Neck. 2013 Aug;35(8):1211-9. 
  8. Hutcheson KA1, Yuk MM, Holsinger FC, Gunn GB, Lewin JS. Late radiation-associated dysphagia with lower cranial neuropathy in long-term oropharyngeal cancer survivors: video case reports. Head Neck. 2015 Apr;37(4):E56-62.

Pharmacology

Learning Objectives 
  1. Explain the use of cisplatin-based chemotherapy, cetuximab and checkpoint inhibitors in the treatment of oropharynx cancer.
  2. Describe the mechanism of action and most common toxicities of cisplatin, cetuximab and checkpoint inhibitors pembrolizumab and nivolumab.
References 
  1. Medina PJ, Adams VR. PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses. Pharmacotherapy. 2016 Mar;36(3):317-34. 
  2. Mackiewicz J, Rybarczyk-Kasiuchnicz A, Lasinska I, Mazur-Roszak M, Swiniuch D, Michalak M, Kazmierska J, Studniarek A, Krokowicz L, Bajon T. The comparison of acute toxicity in 2 treatment courses: Three-weekly and weekly cisplatin treatment administered with radiotherapy in patients with head and neck squamous cell carcinoma. Medicine (Baltimore). 2017 Dec;96(51):e9151. 
  3. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. Jan;11(1):21-8. 
  4. Ferris RL et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov;375:1856-1867.

Surgical Therapies

Learning Objectives 
  1. Explain transoral techniques for surgical treatment of oropharynx neoplasms (TORS and TLM).
  2. Describe limitations of transoral techniques for management of oropharynx cancer including contraindications to transoral surgery.
  3. Review traditional combined transoral / transcervical approachs to the oropharynx including the mandibular split, lingual release and lateral pharyngtomy approaches.
References 
  1. Moore EJ and Hinni ML. Critical Review: Transoral Laser Microsurgery and Robotic-Assisted Surgery for Oropharynx Cancer Including Human Papilloma virus Related Cancer. Int J Radiation Oncol Biol Phys. 2013 Apr 1; 85(5):1163-1167.
  2. Weinstein et al. Understanding contraindications for transoral robotic surgery (TORS) for oropharyngeal cancer. European Archives of Oto-Rhino-Laryngology. 2015 Jul;272(7):1551–1552.

Rehabilitation

Learning Objectives 
  1. Describe the methods used to rehabilitate swallowing function in patients who have undergone surgical or non-surgical treatment of oropharynx cancer.
  2. Cite the functional complications of external beam radiotherapy for treatment of oropharynx cancer.
References 
  1. Tippett DC, Webster KT. Rehabilitation needs of patients with oropharyngeal cancer. Otolaryngol Clin North Am. 2012 Aug;45(4):863-78. 
  2. Paleri V, Roe JW, Strojan P, Corry J, Grégoire V, Hamoir M, Eisbruch A, Mendenhall WM, Silver CE, Rinaldo A, Takes RP, Ferlito A. Strategies to reduce long-term postchemoradiation dysphagia in patients with head and neck cancer: an evidence-based review. Head Neck. 2014 Mar;36(3):431-43. 
  3. Lazarus CL, Husaini H, Falciglia D, DeLacure M, Branski RC, Kraus D, Lee N, Ho M, Ganz C, Smith B, Sanfilippo N. Effects of exercise on swallowing and tongue strength in patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy. Int J Oral Maxillofac Surg. 2014 May;43(5):523-30. 
     

Staging

Learning Objectives 
  1. Review the most current AJCC staging system for HPV-positive and HPV-negative oropharynx cancer.
References 
  1. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR. (Eds.) AJCC Cancer Staging Manual. Springer International Publishing, New York City; 2017. 

Case Studies

  1. A 65 year old man referred for a chief complaint of left neck mass.  He states the mass has been present for at least 3 months. Physical exam reveals a pedunculated lesion in the inferior tongue base that does not extend to the vallecula but does cross midline. Additionally, palpable adenopathy in the left level IIA of the neck that is nontender and mobile is appreciated.
      1. What additional testing is appropriate?
      2. Direct laryngoscopy with biopsy versus fine needle aspiration of the left neck node would be appropriate. Excisional or incisional biopsy of the neck should be avoided
      3. CT of the neck with contrast to determine the extent of tongue base involvement and nodal disease.  Assessment of distant metastatic disease is appropriate and either a PET/CT or a CT chest could be obtained.
    2. Imaging reveals ipsilateral necrotic nodes and exophytic tongue base primary tumor. Fine needle aspiration of one the neck nodes reveals p16+ poorly differentiated squamous cell carcinoma.
      1. What is the stage of disease according to AJCC 8th edition 
        1. cT2N1M0 Stage I
    3. What are treatment options?
      1. Multidisciplinary review at a tumor board and/or consultations with colleagues in Medical and Radiation Oncology should be obtained.
      2. Options are surgery or concurrent chemotherapy and radiation. Surgery would involve transoral (TORS or TLM) resection of the primary tumor and bilateral neck dissection to include at least levels II-IV. Bilateral dissection is indicated because the tumor crosses the midline. Non-surgical option with concurrent chemoradiation usually involves IMRT (intensity modulated radiation therapy) to the primary tumor and bilateral necks. The radiation dose to involved areas has typically been 70 Gy. Chemotherapeutic agents used are typically cisplatin or cetuximab.
      3. What are the surgical options if a transoral surgical approach cannot be performed because of issues with exposure (narrow mandible and maxilla, deeply positioned oropharynx, prominent incisors, etc.)? Open surgical approaches to the oropharynx can be performed and one could use either a mandibulotomy with mandible swing approach, lateral pharyngotomy approach or transhyoid pharyngotomy.
    4. Patient opted for surgery and underwent bilateral neck dissections with ligation of the lingual, facial, and distal superior thyroid artery on the left followed by transoral robotic resection of the tongue base. Final pathology revealed a 1.8 cm tumor and nodal disease in ipsilateral levels IIa and III and contralateral level IIa. Margins were negative but 2 of the lymph nodes had gross ENE >5 mm. 
      1. What is the pathological staging according to AJCC 8th edition? pT1N2Mx Stage II
      2. What additional treatment is recommended? Adjuvant radiation with concurrent chemotherapy based on the current treatment guidelines for ENE.
      3. What are some of the indications for adjuvant treatment if a primary surgical approach is taken? Positive margins, extranodal extension, nodes in levels IV or V and contralateral nodal disease. Refer to current version of NCCN guidelines at https://www.nccn.org/professionals/physician_gls/default.aspx#site
    5. Assuming, this patient has impaired renal function and moderate to severe SNHL, would cisplatin or cetuximab be more appropriate for adjuvant chemoradiation?
    6. Since adjuvant radiation is expected to be needed at the outset, why not just use chemoradiation instead of surgery followed by chemoradiation?
      1. Adjuvant radiation dose is lower (typically 60 Gy) than dose used for primary radiation which is 70 Gy. Swallowing dysfunction with radiation is dose dependent.
    7. Follow up of cancer patients is important to detect locoregional recurrence as well as distant disease./ Patients who receive radiation are at risk of hypothyroidism and should have annual TSH screening
  2. 68 year old male with 12 weeks of left-sided throat pain which is sharp and has been progressing. He reports 50 lb weight loss due to significant odynophagia. No dysphonia or hemoptysis. He reports issues with hearing out of his left ear but is not having pain in that ear. He has 40 pack year history of smoking and currently continues to smoke. Physical exam and review of CT neck with contrast reveals a 3 cm ulcerative lesion of the left tonsillar fossa. The adjacent base of tongue and glossotonsillar sulcus are not involved. There is a 2 cm centrally necrotic lymph node appreciated in left level IIa. 
    1. What additional testing and work up would be appropriate?
      1. Direct laryngoscopy with biopsy to confirm a diagnosis and to determine the extent of disease.
      2. Given the patient’s smoking history and the presence of an oropharyngeal malignancy, a metastatic versus secondary primary work-up should be completed with CT chest with contrast or PET/CT.  
      3. Swallow evaluation by speech pathology and dental evaluation are both recommended. 
      4. Nutritional evaluation is important to assess for protein-calorie malnutrition which can impair wound healing and lead to poorer outcomes
    2. Metastatic work up did not reveal any distant metastatic disease or second primaries.  Biopsy of the tonsillar lesion revealed moderately differentiated squamous cell carcinoma that is p16 negative. What is the stage of disease according to AJCC 8th edition?
      1. T2N1M0
      2. AJCC Stage III
    3. What are the treatment options
      1. Multidisciplinary review at a tumor board and/or consultations with colleagues in Medical and Radiation Oncology should be obtained.
      2. Options are surgery or concurrent chemotherapy and radiation. Surgery would involve transoral (TORS or TLM) resection of the primary tumor and ipsilateral neck dissection to include at least levels II-IV.
      3. Non-surgical option would be radiation therapy alone or in combination with either cisplatin or cetuximab. External beam radiation treatment typically involves IMRT (intensity modulated radiation therapy) to the primary tumor and ipsilateral neck. The radiation dose to involved areas is usually 70 Gy. 
      4. The course of the carotid artery should be noted because aberrant retropharyngeal carotid artery course can preclude a safe transoral approach. What surgical approach could one use in such a case? A mandibulotomy mandible swing approach could be used so that the carotid artery is identified in the neck and the primary is excised via an open approach.
    4. Patient opted for surgery and underwent transoral resection with ipsilateral neck dissection.  Final pathology revealed a 2.8 cm ulcerative tumor in the tonsil excised with negative margins. Immnohistochemistry was performed on the tumor specimen and was negative for p16. There was a single 2 cm lymph node positive for metastatic carcinoma in level IIa. There was no ENE, perineural or lymphovascular invasion. 
      1. What is the pathological stage of the disease? pT1N1Mx Stage III
      2. What additional treatment is recommended? Since there were no adverse features on the final pathology, no adjuvant treatment is recommended.
      3. Follow-up of cancer patients such as these is important. To monitor for locoregional recurrence and for development of second primaries
      4. Smoking cessation counseling is important preoperatively and at follow-up visits

Complications

Learning Objectives 
  1. Review the most common complications of surgery of the oropharynx including catastrophic bleeding, trismus, taste alteration, velopharyngeal insufficiency and describe ways to prevent and manage them.
References 
  1. Asher SA, White HN, Kejner AE, Rosenthal EL, Carroll WR, Magnuson JS. Hemorrhage after transoral robotic-assisted surgery. Otolaryngol Head Neck Surg. 2013 Jul;149(1):112-7.
  2. Mandal R, Duvvuri U, Ferris RL, Kaffenberger TM, Choby GW, Kim S. Analysis of post-transoral robotic-assisted surgery hemorrhage: frequency, outcomes, and prevention. Head Neck. 2016;38(1):E776–82. 
  3. Pollei TR, Hinni ML, Moore EJ, Hayden RE, Olsen KD, Casler JD, et al. Analysis of postoperative bleeding and risk factors in transoral surgery of the oropharynx. JAMA Otolaryngol Head Neck Surg. 2013;139(11):1212–8.

Review

Review Questions 
  1. Which is more likely to initially present with a large nodal metastasis without any other symptoms?
    • Mucoepidermoid carcinoma of the base of tongue
    • OPSCC HPV+
    • OPSCC HPV-
    • Lingual thyroid
  2. Which of the following methods can be used to confirm that an OPSCC is HPV-related? Choose all that apply
    • Immunohistochemistry for p16 protein
    • In situ hybridization with HPV DNA probes
    • Serology for HPV-specific IgM antibodies
    • Serology for HPV-specific IgG antibodies
  3. Which of the following vessels should be ligated prior to transoral resection of a T2 OPSCC? Choose all that apply
    • Lingual artery
    • Facial artery
    • Superior thyroid
    • Inferior thyroid
Resources 

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