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Management of Unknown Primary Cancer of the Head and Neck

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Difficult Decisions in Head and Neck Oncologic Surgery

Part of the book series: Difficult Decisions in Surgery: An Evidence-Based Approach ((DDSURGERY))

Abstract

Head and neck cancer with an unknown primary site (CUP) often presents as an asymptomatic, enlarging neck mass, which is then confirmed to represent metastatic nodal disease. These cancers are encountered with increasing frequency in many head and neck surgical oncology practices. The majority of CUP occurs in patients over age 40 years, and is most frequently suspected as having an oropharyngeal primary site, and a causal association with high-risk human papillomavirus infection. The majority of patients diagnosed with CUP on initial presentation, will have a detectable primary tumor after thorough diagnostic evaluation, either within the tongue base or palatine tonsil. A comprehensive diagnostic evaluation and understanding of the advantages and disadvantages of treatment options is essential to serve patients with the best oncologic outcomes and least morbidity possible. In this chapter, we review contemporary research advancing the evaluation and management of CUP. As head and neck squamous cell carcinoma is the most commonly encountered histopathology of CUP, the majority of this chapter focuses on this form of cancer.

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References

  1. Grau C, Johansen LV, Jakobsen J, Geertsen P, Andersen E, Jensen BB. Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiother Oncol. 2000;55(2):121–9.

    Article  CAS  Google Scholar 

  2. Network NCC. NCCN Clinical Practice Guidelines in Oncology (Head and Neck Cancers). 2018;Version 1.2018.

    Google Scholar 

  3. Keller LM, Galloway TJ, Holdbrook T, et al. p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary. Head Neck. 2014;36(12):1677–84.

    Article  Google Scholar 

  4. Motz K, Qualliotine JR, Rettig E, Richmon JD, Eisele DW, Fakhry C. Changes in unknown primary squamous cell carcinoma of the head and neck at initial presentation in the era of human papillomavirus. JAMA Otolaryngol Head Neck Surg. 2016;142(3):223–8.

    Article  Google Scholar 

  5. Nieder C, Gregoire V, Ang KK. Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys. 2001;50(3):727–33.

    Article  CAS  Google Scholar 

  6. Mizuta M, Kitamura M, Tateya I, et al. Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases. Acta Otolaryngol. 2018;138(6):590–6.

    Article  Google Scholar 

  7. Balaker AE, Abemayor E, Elashoff D, St John MA. Cancer of unknown primary: does treatment modality make a difference? Laryngoscope. 2012;122(6):1279–82.

    Article  Google Scholar 

  8. Kamal M, Mohamed ASR, Fuller CD, et al. Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy. Cancer. 2018;124(7):1415–27.

    Article  Google Scholar 

  9. Wallace A, Richards GM, Harari PM, et al. Head and neck squamous cell carcinoma from an unknown primary site. Am J Otolaryngol. 2011;32(4):286–90.

    Article  Google Scholar 

  10. Aslani M, Sultanem K, Voung T, Hier M, Niazi T, Shenouda G. Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: is there a need for neck dissection? Head Neck. 2007;29(6):585–90.

    Article  Google Scholar 

  11. Chen AM, Meshman J, Hsu S, Yoshizaki T, Abemayor E, John MS. Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin. Head Neck. 2018;40(2):227–32.

    Article  Google Scholar 

  12. Galloway TJ, Ridge JA. Management of squamous cancer metastatic to cervical nodes with an unknown primary site. J Clin Oncol. 2015;33(29):3328–37.

    Article  CAS  Google Scholar 

  13. Muraki AS, Mancuso AA, Harnsberger HR. Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology. 1984;152(3):749–53.

    Article  CAS  Google Scholar 

  14. Nakamoto Y, Tatsumi M, Hammoud D, Cohade C, Osman MM, Wahl RL. Normal FDG distribution patterns in the head and neck: PET/CT evaluation. Radiology. 2005;234(3):879–85.

    Article  Google Scholar 

  15. Cianchetti M, Mancuso AA, Amdur RJ, et al. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Laryngoscope. 2009;119(12):2348–54.

    Article  Google Scholar 

  16. Keller F, Psychogios G, Linke R, et al. Carcinoma of unknown primary in the head and neck: comparison between positron emission tomography (PET) and PET/CT. Head Neck. 2011;33(11):1569–75.

    Article  Google Scholar 

  17. Rudmik L, Lau HY, Matthews TW, et al. Clinical utility of PET/CT in the evaluation of head and neck squamous cell carcinoma with an unknown primary: a prospective clinical trial. Head Neck. 2011;33(7):935–40.

    Article  Google Scholar 

  18. Patel SA, Magnuson JS, Holsinger FC, et al. Robotic surgery for primary head and neck squamous cell carcinoma of unknown site. JAMA Otolaryngol Head Neck Surg. 2013;139(11):1203–11.

    Article  Google Scholar 

  19. Kuta V, Williams B, Rigby M, et al. Management of head and neck primary unknown squamous cell carcinoma using combined positron emission tomography-computed tomography and transoral laser microsurgery. Laryngoscope. 2018;128(10):2307–11.

    Article  Google Scholar 

  20. Kobayashi K, Saito Y, Omura G, et al. Clinical features of human papilloma virus-related head and neck squamous cell carcinoma of an unknown primary site. ORL J Otorhinolaryngol Relat Spec. 2014;76(3):137–46.

    Article  Google Scholar 

  21. Jensen DH, Hedback N, Specht L, et al. Human papillomavirus in head and neck squamous cell carcinoma of unknown primary is a common event and a strong predictor of survival. PLoS One. 2014;9(11):e110456.

    Article  Google Scholar 

  22. Conscience I, Jovenin N, Coissard C, et al. P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas. Eur J Dermatol. 2006;16(5):518–22.

    CAS  PubMed  Google Scholar 

  23. Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32(5):562–7.

    PubMed  PubMed Central  Google Scholar 

  24. Jannapureddy S, Cohen C, Lau S, Beitler JJ, Siddiqui MT. Assessing for primary oropharyngeal or nasopharyngeal squamous cell carcinoma from fine needle aspiration of cervical lymph node metastases. Diagn Cytopathol. 2010;38(11):795–800.

    Article  Google Scholar 

  25. Beadle BM, William WN Jr, McLemore MS, Sturgis EM, Williams MD. p16 expression in cutaneous squamous carcinomas with neck metastases: a potential pitfall in identifying unknown primaries of the head and neck. Head Neck. 2013;35(11):1527–33.

    Article  Google Scholar 

  26. Coster JR, Foote RL, Olsen KD, Jack SM, Schaid DJ, DeSanto LW. Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys. 1992;23(4):743–9.

    Article  CAS  Google Scholar 

  27. 3311 E. Phase II randomized trial of transoral surgical resection followed by low-dose or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer (E3311).

    Google Scholar 

  28. Patel SA, Parvathaneni A, Parvathaneni U, et al. Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck. Oral Oncol. 2017;72:150–6.

    Article  Google Scholar 

  29. Geltzeiler M, Doerfler S, Turner M, et al. Transoral robotic surgery for management of cervical unknown primary squamous cell carcinoma: updates on efficacy, surgical technique and margin status. Oral Oncol. 2017;66:9–13.

    Article  Google Scholar 

  30. Mehta V, Johnson P, Tassler A, et al. A new paradigm for the diagnosis and management of unknown primary tumors of the head and neck: a role for transoral robotic surgery. Laryngoscope. 2013;123(1):146–51.

    Article  Google Scholar 

  31. Nagel TH, Hinni ML, Hayden RE, Lott DG. Transoral laser microsurgery for the unknown primary: role for lingual tonsillectomy. Head Neck. 2014;36(7):942–6.

    Article  Google Scholar 

  32. Graboyes EM, Sinha P, Thorstad WL, Rich JT, Haughey BH. Management of human papillomavirus-related unknown primaries of the head and neck with a transoral surgical approach. Head Neck. 2015;37(11):1603–11.

    Article  Google Scholar 

  33. Durmus K, Rangarajan SV, Old MO, Agrawal A, Teknos TN, Ozer E. Transoral robotic approach to carcinoma of unknown primary. Head Neck. 2014;36(6):848–52.

    Article  Google Scholar 

  34. Jesse RH, Perez CA, Fletcher GH. Cervical lymph node metastasis: unknown primary cancer. Cancer. 1973;31(4):854–9.

    Article  CAS  Google Scholar 

  35. Mourad WF, Hu KS, Shasha D, et al. Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck. Anticancer Res. 2014;34(1):243–8.

    PubMed  Google Scholar 

  36. Colletier PJ, Garden AS, Morrison WH, Goepfert H, Geara F, Ang KK. Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck. 1998;20(8):674–81.

    Article  CAS  Google Scholar 

  37. Reddy SP, Marks JE. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation. Int J Radiat Oncol Biol Phys. 1997;37(4):797–802.

    Article  CAS  Google Scholar 

  38. Perkins SM, Spencer CR, Chernock RD, et al. Radiotherapeutic management of cervical lymph node metastases from an unknown primary site. Arch Otolaryngol Head Neck Surg. 2012;138(7):656–61.

    Article  Google Scholar 

  39. Marcial-Vega VA, Cardenes H, Perez CA, et al. Cervical metastases from unknown primaries: radiotherapeutic management and appearance of subsequent primaries. Int J Radiat Oncol Biol Phys. 1990;19(4):919–28.

    Article  CAS  Google Scholar 

  40. Sinnathamby K, Peters LJ, Laidlaw C, Hughes PG. The occult head and neck primary: to treat or not to treat? Clin Oncol (R Coll Radiol). 1997;9(5):322–9.

    Article  CAS  Google Scholar 

  41. Glynne-Jones RG, Anand AK, Young TE, Berry RJ. Metastatic carcinoma in the cervical lymph nodes from an occult primary: a conservative approach to the role of radiotherapy. Int J Radiat Oncol Biol Phys. 1990;18(2):289–94.

    Article  CAS  Google Scholar 

  42. Weir L, Keane T, Cummings B, et al. Radiation treatment of cervical lymph node metastases from an unknown primary: an analysis of outcome by treatment volume and other prognostic factors. Radiother Oncol. 1995;35(3):206–11.

    Article  CAS  Google Scholar 

  43. Ross RB, Koyfman SA, Reddy CA, et al. A matched comparison of human papillomavirus-induced squamous cancer of unknown primary with early oropharynx cancer. Laryngoscope. 2018;128(6):1379–85.

    Article  Google Scholar 

  44. Ozbay I, Yumusakhuylu AC, Sethia R, et al. One-year quality of life and functional outcomes of transoral robotic surgery for carcinoma of unknown primary. Head Neck. 2017;39(8):1596–602.

    Article  Google Scholar 

  45. Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer. 2004;101(11):2641–9.

    Article  Google Scholar 

  46. A. Argiris, (2003) Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary. Annals of Oncology 14(8):1306–11.

    Google Scholar 

  47. Demiroz C, Vainshtein JM, Koukourakis GV, et al. Head & Neck Squamous Cell Carcinoma of Unknown Primary: Neck Dissection and Radiotherapy or Definitive Radiotherapy. Head&Neck. 2014; 36(11): 1589–95.

    Google Scholar 

  48. Michael Huo, Benedict Panizza, Anne Bernard, Sandro V. Porceddu, (2018) Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer. Oral Oncology 77:43–48.

    Google Scholar 

  49. De Ridder M, Klop M, Hamming-Vrieze O, et al. Unknown primary head and neck squamous cell carcinoma in the era of fluorodeoxyglucosepositron emission tomography/ CT and intensity-modulated radiotherapy. Head & Neck. 2017;39:1382–91.

    Google Scholar 

  50. Lachlan J. McDowell, Richard J. Young, Meredith L. Johnston, Tze-Jian Tan, Stephen Kleid, Chen S. Liu, Mathias Bressel, Vanessa Estall, Danny Rischin, Benjamin Solomon, June Corry, (2016) p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary. Cancer 122 (8):1201–08.

    Google Scholar 

  51. John Cuaron, Shyam Rao, Suzanne Wolden, Michael Zelefsky, Karen Schupak, Borys Mychalczak, Nancy Lee, (2016) Patterns of failure in patients with head and neck carcinoma of unknown primary treated with radiation therapy. Head & Neck 38 (S1):E426-E431.

    Google Scholar 

  52. Hatten KM, O’Malley BW Jr, Bur AM, et al. Transoral robotic surgery-assisted endoscopy with primary site detection and treatment in occult mucosal primaries. JAMA Otolaryngol Head Neck Surg. 2017;143(3):267–73.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Head and Neck Surgery, Orlando Health UF Health Cancer Center, Orlando, FL, USA

    Jennifer Christenson

  2. Department of Otolaryngology—Head and Neck Surgery, Oregon Health & Science University, Portland, OR, USA

    Ryan J. Li

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  1. Jennifer Christenson
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  2. Ryan J. Li
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Correspondence to Ryan J. Li .

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Editors and Affiliations

  1. Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA

    Zhen Gooi

  2. Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA

    Nishant Agrawal

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Christenson, J., Li, R.J. (2019). Management of Unknown Primary Cancer of the Head and Neck. In: Gooi, Z., Agrawal, N. (eds) Difficult Decisions in Head and Neck Oncologic Surgery. Difficult Decisions in Surgery: An Evidence-Based Approach. Springer, Cham. https://doi.org/10.1007/978-3-030-15123-2_9

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  • DOI: https://doi.org/10.1007/978-3-030-15123-2_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-15122-5

  • Online ISBN: 978-3-030-15123-2

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