Objective: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. Methods: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. Results: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). Conclusion: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds): AJCC Cancer Staging Manual, ed 7. New York, Springer, 2010.
Langer CJ: Exploring biomarkers in head and neck cancer. Cancer 2012;118:3882-3892.
Ferreira MB, De Souza JA, Cohen EE: Role of molecular markers in the management of head and neck cancers. Curr Opin Oncol 2011;23:259-264.
Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, Oggionni M, Rossini C, Cantù G, Squadrelli M, Quattrone P, Locati LD, Bergamini C, Olmi P, Pierotti MA, Pilotti S: High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 2006;24:5630-5636.
Knegjens JL, Hauptmann M, Pameijer FA, Balm AJ, Hoebers FJ, de Bois JA, Kaanders JH, van Herpen CM, Verhoef CG, Wijers OB, Wiggenraad RG, Buter J, Rasch CR: Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer. Head Neck 2010;33:375-382.
Pameijer FA, Mancuso AA, Mendenhall WM, Parsons JT, Kubilis PS: Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottis larynx treated with definitive radiotherapy? Int J Radiat Oncol Biol Phys 1997;37:1011-1021.
Kao J, Lavaf A, Teng MS, Huang D, Genden EM: Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage. Int J Radiat Oncol Biol Phys 2008;71:362-370.
Woolgar JA: Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncol 2006;42:229-239.
Grabenbauer GG, Steininger H, Meyer M, Fietkau R, Brunner T, Heinkelmann P, Hornung J, Iro H, Spitzer W, Kirchner T, Sauer R, Distel L: Nodal CT density and total tumor volume as prognostic factors after radiation therapy of stage III/IV head and neck cancer. Radiother Oncol 1998;47:175-183.
Desai PC, Jaglal MV, Gopal P, Ghim SJ, Miller DM, Farghaly H, Jenson AB: Human papillomavirus in metastatic squamous carcinoma from unknown primaries in the head and neck: a retrospective 7 year study. Exp Mol Pathol 2009;87:94-98.
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 Neck Oncology. Radiother Oncol 2000;55:121-129.
Koo JS, Kim H: Hypoxia-related protein expression and its clinicopathologic implication in carcinoma of unknown primary. Tumour Biol 2011;32:893-904.
Nakamura T, Sumi M: Nodal imaging in the neck: recent advances in US, CT and MR imaging of metastatic nodes. Eur Radiol 2007;17:1235-1241.
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;9:322-329.
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;37:797-802.
Park GC, Lee M, Roh JL, Yu MS, Choi SH, Nam SY, Kim SY, Cho KJ: Human papillomavirus and p16 detection in cervical lymph node metastases from an unknown primary tumor. Oral Oncol 2012;48:1250-1256.
Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E: Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 2000;89:300-304.
Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML: Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 2008;100:261-269.
Compton AM, Moore-Medlin T, Herman-Ferdinandez L, Clark C, Caldito GC, Wang XI, Thomas J, Abreo FW, Nathan CO: Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2011;145:51-57.
Vergeer MR, Doornaert P, Leemans CR, Buter J, Slotman BJ, Langendijk JA: Control of nodal metastases in squamous cell head and neck cancer treated by radiation therapy or chemoradiation. Radiother Oncol 2006;79:39-44.
Plataniotis GA, Theofanopoulou ME, Kalogera-Fountzila A, Haritanti A, Ciuleanou E, Ghilezan N, Zamboglou N, Dimitriadis A, Sofroniadis I, Fountzilas G: Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial. Int J Radiat Oncol Biol Phys 2004;59:1018-1026.
Herr HW: Superiority of ratio based lymph node staging bladder cancer. J Urol 2003;169:943-945.
Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, Makowiec F: The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg 2009;13:1337-1344.
Vaccaro CA, Im V, Rossi GL, Quintana GO, Benati ML, Perez de Arenaza D, Bonadeo FA: Lymph node ratio as prognostic factor for colon cancer treated by colorectal surgeons. Dis Colon Rectum 2009;52:1244-1250.
Kim SY, Nam SY, Choi SH, Cho KJ, Roh JL: Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma. Ann Surg Oncol 2011;18:2310-2317.
Ebrahimi A, Clark JR, Zhang WJ, Elliott MS, Gao K, Milross CG, Shannon KF: Lymph node ratio as an independent prognostic factor in oral squamous cell carcinoma. Head Neck 2011;33:1245-1251.
King B, Corry J: Pathology reporting in head and neck cancer-snapshot of current status. Head Neck 2009;31:227-231.
Rödel RM, Matthias C, Blomeyer BD, Wolff HA, Jung K, Christiansen H: Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site. Ann Otol Rhinol Laryngol 2009;118:662-669.
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