REVIEW ARTICLE
Oncology
doi: 10.25005/2074-0581-2025-27-1-136-142
METASTATIC HEAD AND NECK CANCER WITH UNKNOWN PRIMARY: DIAGNOSIS AND TREATMENT

M.I. SOKOLOVA¹, V.I. PAVLOVA²

1Multidisciplinary Clinical Medical Center "Medical City", Tyumen, Russian Federation
2Tyumen State Medical University, Tyumen, Russian Federation

The availability of a wide range of modern diagnostic methods for identifying primary tumors in patients with metastases of unknown origin creates challenges in determining the optimal sequence for their use. This issue can often result in delays in the initiation of treatment. This review article aims to organize contemporary approaches for identifying the primary tumor and provides practical recommendations based on an analysis of current scientific data. The search was conducted in the EMBASE, MEDLINE, PubMed, and CINAHL databases from 2009 to 2023, using keywords such as squamous cell carcinoma, primary focus, metastases to the neck lymph nodes, transoral surgery, and p16 expression. During the preliminary analysis of the available literature, studies that did not address the relevant aspects of this research were excluded. All primary research articles focused on diagnosing and treating patients with metastases of unknown origin were included in the study.

Keywords: Squamous cell carcinoma, primary lesion, metastases to the lymph nodes of the neck, transoral surgery, p16 expression.

Download file:

References
  1. Meccariello G, Cammaroto G, Ofo E, Calpona S, Parisi E, D'Agostino G, et al. The emerging role of trans-oral robotic surgery for the detection of the primary tumour site in patients with head-neck unknown primary cancers: A metaanalysis. Auris Nasus Larynx. 2019;46(5):663-71. https://doi.org/10.1016/j. anl.2019.04.007
  2. Bhide SP, Katre RY, Joshi SR. Cytological evaluation of fine needle aspiration cytology in lymph node lesions. J Med Sci Clin Res. 2017;5(8):26869-76. https:// doi.org/10.18535/jmscr/v5i8.147
  3. Ferreira VH, Sassi LM, Zanicotti RS, Ramos GA, Jung JE, Schussel JL, et al. Core needle biopsy in the diagnosis of head and neck lesions: A retrospective study of 3 years. Eur Arch Otorhinolaryngol. 2016;273(12):4469-72. https://doi. org/10.1007/s00405-016-4139-6
  4. Faisal M, Le NS, Grasl S, Pammer J, Janik S, Heiduschka G, et al. Survival outcome in true carcinoma of unknown primary (tCUP) with p16+ cervical metastasis. Int Arch Otorhinolaryngol. 2023;27(4):687-93. https://doi.org/10.1055/s-0042-1759575
  5. Maghami E, Ismaila N, Alvarez A, Chernock R, Duwuri U, Geiger J, et al. Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO Guideline. J Clin Oncol. 2020; 38:2570-96. https://doi. org/10.1200/JCO.20.00275
  6. Cheol Park G, Roh JL, Cho KJ, Seung Kim J, Hyeon Jin M, Choi SH, et al. F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors. Cancer. 2017;140(6):1405-12. https://doi.org/10.1002/ijc.30550
  7. Ruhlmann V, Ruhlmann M. Hybrid imaging for detection of carcinoma of unknown primary: A preliminary comparison trial of whole-body PET/MRI versus PET/CT. Eur J Radiol. 2016;85(11):1941-7. https://doi.org/10.1016/j. ejrad.2016.08.020
  8. Gelezhe PV. Modern criteria of radiation diagnostics in assessing the effectiveness of special antitumor treatment. Russian Oncology Journal. 2014;3:39-46.
  9. Meenakkshy M, Noah S. Head and neck squamous cell carcinoma of unknown primary. A diagnostic work-up. The Oncologist. 2024;29(3):192-9. https://doi. org/10.1093/oncolo/oyad311
  10. Keller L, Galloway T, Holdbrook T, Ruth K, Yang D, Dubyk C, et al. Р16 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. https://doi.org/10.1002/hed.23514
  11. Waltonen JD, Ozer E, Hall NC, Schuller DE, Agrawal A. Metastatic carcinoma of the neck of unknown primary origin: Evolution and efficacy of the modern workup. Arch Otolaryngol Head Neck Surg. 2009;135(10):1024-9. https://doi. org/10.1001/archoto.2009.145
  12. Sokoya M, Chowdhury F, Kadakia S, Ducic Y. Combination of panendoscopy and positron emission tomography/computed tomography increases detection of unknown primary head and neck carcinoma. Laryngoscope. 2018;128(11):2573- 5. https://doi.org/10.1002/lary.2726
  13. Abu-Shama Y, Salleron J, Carsuzaa F, Sun XS, Pflumio C, Troussier I, et al. Impact of neck dissection in head and neck squamous cell carcinomas of unknown primary. Cancers (Basel). 2021;13(10):2416. https://doi.org/10.3390/cancers13102416
  14. Demiroz C, Vainshtein JM, Koukourakis GV, Gutfeld O, Prince ME, Bradford CR, et al. Head and neck squamous cell carcinoma of unknown primary: Neck dissection and radiotherapy or definitive radiotherapy. Head Neck. 2014;36(11):1589-95. https://doi.org/10.1002/hed.23479
  15. Balk M, Rupp R, Mantsopoulos K, Sievert M, Gostian M, Allner M, et al. Factors influencing the outcome of head and neck cancer of unknown primary (HNCUP). J Clin Med. 2022;11(10):2689. https://doi.org/10.3390/jcm11102689
  16. Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, et al. Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022;33(2):216-26. https://doi.org/10.1016/j.annonc.2021.11.009
  17. Ofo E, Spiers H, Kim D, Duvvuri U. Transoral robotic surgery and the unknown primary. ORL J Otorhinolaryngol Relat Spec. 2018;80(3-4):148-55. https://doi. org/10.1159/000490596
  18. Mistry R, Walke A, Kim D, Ofo E. Transoral robotic surgery for the benefit of patients with head and neck cancer of unknown primary: Our experience at St George’s University Hospital, London. Ann R Coll Surg Engl. 2020;102(6):442- 450. https://doi.org/10.1308/rcsann.2020.0071
  19. Fu TS, Foreman A, Goldstein DP, de Almeida JR. The role of transoral robotic surgery, transoral laser microsurgery, and lingual tonsillectomy in the identification of head and neck squamous cell carcinoma of unknown primary origin: A systematic review. J Otolaryngol Head Neck Surg. 2016;45(1):28. https://doi.org/10.1186/s40463-016-0142-6
  20. Davies-Husband CR. Tongue base mucosectomy for carcinoma of unknown primary using endoscopic electrocautery: Rationale for wider implementation of an institutionally restricted technique. J Laryngol Otol. 2018;132(12):1138-42. https://doi.org/10.1017/S0022215118002062
  21. Weyers BW, Birkeland AC, Marsden MA, Tam A, Bec J, Frusciante RP, et al. Intraoperative delineation of p16+ oropharyngeal carcinoma of unknown primary origin with fluorescence lifetime imaging: Preliminary report. Head Neck. 2022;44(8):1765-6. https://doi.org/10.3390/cancers15030896
  22. Wong EYT, Lim JFY, Toh HC. A review on paying for advanced cancer therapeutics: Hard truths and realities in Asia. Chinese Clinical Oncology. 2023;12(4):40. https://doi.org/10.21037/cco-23-37
  23. Brandt B, Levin G, Leitao Jr MM. Radical hysterectomy for cervical cancer: The right surgical approach. Current Treatment Options in Oncology. 2022;23(1):1- 14. https://doi.org/10.1007/s11864-021-00919-z
  24. Kokka F, Bryant A, Olaitan A, Brockbank E, Powell M, Oram D. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. The Cochrane Database of Systematic Reviews. 2022;8(8):CD010260. https://doi.org/10.1002/14651858.CD010260.pub3
  25. Pareja R. Surgical staging for locally-advanced cervical cancer: The answer remains 'NO'. International Journal of Gynecological Cancer. 2022;32(7):828-9. https://doi.org/10.1136/ijgc-2022-003713
  26. Llueca A, Escrig J, Gil-Moreno A, Benito V, Hernández A, Díaz-Feijoo B, et al. The extent of aortic lymphadenectomy in locally advanced cervical cancer impacts on survival. Journal of Gynecologic Oncology. 2021;32(1):e4. https://doi. org/10.3802/jgo.2021.32.e4
  27. Niikura H, Tsuji K, Tokunaga H, Shimada M, Ishikawa M, Yaegashi N. Sentinel node navigation surgery in cervical and endometrial cancer: A review. Japanese Journal of Clinical Oncology. 2019;49(6):495-500. https://doi.org/10.1093/jjco/ hyz062
  28. Rema P, Mathew AP, Suchetha S, Ahmed I. Salvage surgery for cervical cancer recurrences. Indian Journal of Surgical Oncology. 2017;8(2):146-9. https://doi. org/10.1007/s13193-015-0472-2

Authors' information:

Sokolova Maria Ivanovna,
Oncologist of the Department of Head and Neck Tumors, Multidisciplinary Clinical Medical Center "Medical City"
ORCID ID: 0000-0002-9026-1153
SPIN: 6763-2109
E-mail: mascha23.06@mail.ru

Pavlova Valeria Igorevna,
Candidate of Medical Sciences, Associate Professor of the Department of Oncology, Radiology and Radiotherapy, Tyumen State Medical University
ORCID ID: 0000-0002-0899-0809
SPIN: 8525-7207
Аuthor ID: 1173467
E-mail: pavlova.valeria@mail.ru

Information about support in the form of grants, equipment, medications

The authors did not receive financial support from manufacturers of medi- cines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Sokolova Maria Ivanovna
Oncologist of the Department of Head and Neck Tumors, Multidisciplinary Clinical Medical Center "Medical City"

625041, Russian Federation, Tyumen, Barnaulskaya str., 32

Tel.: +7 (904) 4916622

E-mail: mascha23.06@mail.ru


This work is licensed under a Creative Commons Attribution 4.0 International License.

Materials on the topic:
  1. SENTINEL LYMPH NODE BIOPSY IN BREAST CANCER: ONGOING CONSIDERATIONS
  2. ROLE OF RADIATION THERAPY IN COMBINED AND MULTIMODAL TREATMENT OF T3-4N1-2-3M0-1-2 STAGE SKIN CANCER
  3. SURGICAL TREATMENT OF A GIANT RETROPERITONEAL LIPOMA: A CLINICAL CASE
  4. PREOPERATIVE PREDICTION OF WALL INVASION DEPTH OF PRIMARY TUMOR (PT) IN GASTRIC CANCER PATIENTS
  5. CURRENT SURGICAL TREATMENT OPTIONS FOR LATE STAGES OF CERVICAL CANCER
  6. CLINICAL CASE OF BCLC STAGE B HEPATOCELLULAR CARCINOMA WITH A COMBINED TREATMENT
  7. MODERN VIEW ON REHABILITATION OF CANCER PATIENTS
  8. COMPLEX DIAGNOSIS OF CERVICAL INTRAEPITHELIAL NEOPLASIA IN THE REPUBLIC OF TAJIKISTAN
  9. MODERN METHODS OF LOCAL TREATMENT OF PATIENTS WITH UVEAL MELANOMA WITH LIVER METASTASES
  10. FIRST RESULTS OF TREATMENT OF CERVICAL INTRAEPITHELIAL NEOPLASIA IN THE REPUBLIC OF TAJIKISTAN

◄ Back to the list