Top

European Archives of Oto-Rhino-Laryngology

Published in:

01-02-2018 | Head and Neck

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status

Authors: Christian Jacobi, Josepha Rauch, Jan Hagemann, Thomas Lautz, Maximilian Reiter, Philipp Baumeister

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2018

Abstract

Objective

Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system.

Methods

From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis.

Results

137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143).

Conclusion

The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Takes RP, Rinaldo A, Silver CE, Piccirillo JF, Haigentz M Jr, Suarez C, Van der Poorten V, Hermans R, Rodrigo JP, Devaney KO, Ferlito A (2010) Future of the TNM classification and staging system in head and neck cancer. Head Neck 32(12):1693–1711. https://doi.org/10.1002/hed.21361 CrossRefPubMed

Godeny M (2014) Prognostic factors in advanced pharyngeal and oral cavity cancer; significance of multimodality imaging in terms of 7th edition of TNM. Cancer Imaging 14:15. https://doi.org/10.1186/1470-7330-14-15 PubMedPubMedCentral

Patel SG, Shah JP (2005) TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA: Cancer J Clin 55(4):242–258 (quiz 261-242, 264)

Lydiatt WM, Patel SG, O’Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP (2017) Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA: Cancer J Clin. https://doi.org/10.3322/caac.21389

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 (2017) AJCC cancer staging manual. Springer International Publishing, New YorkCrossRef

Dahlstrom KR, Garden AS, William WN Jr, Lim MY, Sturgis EM (2016) Proposed staging system for patients with HPV-related oropharyngeal cancer based on nasopharyngeal cancer N categories. J Clin Oncol 34(16):1848–1854. https://doi.org/10.1200/JCO.2015.64.6448 CrossRefPubMedPubMedCentral

Dahlstrom KR, Calzada G, Hanby JD, Garden AS, Glisson BS, Li G, Roberts DB, Weber RS, Sturgis EM (2013) An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair. Cancer 119(1):81–89. https://doi.org/10.1002/cncr.27727 CrossRefPubMed

Ward MJ, Mellows T, Harris S, Webb A, Patel NN, Cox HJ, Piper K, Ottensmeier CH, Thomas GJ, King EV (2015) Staging and treatment of oropharyngeal cancer in the human papillomavirus era. Head Neck 37(7):1002–1013. https://doi.org/10.1002/hed.23697 CrossRefPubMed

Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, Ringash J, Bayley A, Kim J, Hope A, Cho J, Giuliani M, Hansen A, Irish J, Gilbert R, Gullane P, Perez-Ordonez B, Weinreb I, Liu FF, O’Sullivan B (2015) Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol 33(8):836–845. https://doi.org/10.1200/JCO.2014.58.6412 CrossRefPubMed

10.

Ebrahimi A, Clark JR, Zhang WJ, Elliott MS, Gao K, Milross CG, Shannon KF (2011) Lymph node ratio as an independent prognostic factor in oral squamous cell carcinoma. Head Neck 33(9):1245–1251. https://doi.org/10.1002/hed.21600 CrossRefPubMed

11.

Gil Z, Carlson DL, Boyle JO, Kraus DH, Shah JP, Shaha AR, Singh B, Wong RJ, Patel SG (2009) Lymph node density is a significant predictor of outcome in patients with oral cancer. Cancer 115(24):5700–5710. https://doi.org/10.1002/cncr.24631 CrossRefPubMed

12.

Shrime MG, Bachar G, Lea J, Volling C, Ma C, Gullane PJ, Gilbert RW, Irish JC, Brown DH, Goldstein DP (2009) Nodal ratio as an independent predictor of survival in squamous cell carcinoma of the oral cavity. Head Neck 31(11):1482–1488. https://doi.org/10.1002/hed.21114 CrossRefPubMed

13.

Reinisch S, Kruse A, Bredell M, Lubbers HT, Gander T, Lanzer M (2014) Is lymph-node ratio a superior predictor than lymph node status for recurrence-free and overall survival in patients with head and neck squamous cell carcinoma? Annals of surgical oncology 21. (6):1912–1918. https://doi.org/10.1245/s10434-014-3634-5

14.

Marres CC, de Ridder M, Hegger I, van Velthuysen ML, Hauptmann M, Navran A, Balm AJ (2014) The influence of nodal yield in neck dissections on lymph node ratio in head and neck cancer. Oral oncology 50(1):59–64. https://doi.org/10.1016/j.oraloncology.2013.09.014 CrossRefPubMed

15.

Medina-Franco H, Cabrera-Mendoza F, Almaguer-Rosales S, Guillen F, Suarez-Bobadilla YL, Sanchez-Ramon A (2013) Lymph node ratio as a predictor of survival in gastric carcinoma. The Am Surgeon 79(3):284–289PubMed

16.

Kassouf W, Agarwal PK, Herr HW, Munsell MF, Spiess PE, Brown GA, Pisters L, Grossman HB, Dinney CP, Kamat AM (2008) Lymph node density is superior to TNM nodal status in predicting disease-specific survival after radical cystectomy for bladder cancer: analysis of pooled data from MDACC and MSKCC. J Clin Oncol 26(1):121–126. https://doi.org/10.1200/JCO.2007.12.9247 CrossRefPubMed

17.

Ooki A, Yamashita K, Kobayashi N, Katada N, Sakuramoto S, Kikuchi S, Watanabe M (2007) Lymph node metastasis density and growth pattern as independent prognostic factors in advanced esophageal squamous cell carcinoma. World J Surg 31(11):2184–2191. https://doi.org/10.1007/s00268-007-9198-9 CrossRefPubMed

18.

Kunzel J, Psychogios G, Mantsopoulos K, Grundtner P, Waldfahrer F, Iro H (2014) Lymph node ratio as a predictor of outcome in patients with oropharyngeal cancer. European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies. 271 (5):1171–1180. https://doi.org/10.1007/s00405-013-2513-1 CrossRef

19.

Mallen-St Clair J, Alani M, Wang MB, Srivatsan ES (2016) Human papillomavirus in oropharyngeal cancer: The changing face of a disease. Biochimica et biophysica acta 1866(2):141–150. https://doi.org/10.1016/j.bbcan.2016.07.005 PubMed

20.

Mendelsohn AH, Lai CK, Shintaku IP, Elashoff DA, Dubinett SM, Abemayor E, St John MA (2010) Histopathologic findings of HPV and p16 positive HNSCC. Laryngoscope 120(9):1788–1794. https://doi.org/10.1002/lary.21044 CrossRefPubMed

21.

Kim SY, Nam SY, Choi SH, Cho KJ, Roh JL (2011) Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma. Ann Surg Oncol 18(8):2310–2317. https://doi.org/10.1245/s10434-011-1614-6 CrossRefPubMed

22.

Ong W, Zhao R, Lui B, Tan W, Ebrahimi A, Clark JR, Soo KC, Tan NC, Tan HK, Iyer NG (2016) Prognostic significance of lymph node density in squamous cell carcinoma of the tongue. Head neck 38(Suppl 1):E859–E866. https://doi.org/10.1002/hed.24113 CrossRefPubMed

23.

Lewis JS Jr (2012) p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol 6(Suppl 1):S75–S82. https://doi.org/10.1007/s12105-012-0369-0 CrossRefPubMed

24.

Westra WH (2014) Detection of human papillomavirus (HPV) in clinical samples: evolving methods and strategies for the accurate determination of HPV status of head and neck carcinomas. Oral Oncol 50(9):771–779. https://doi.org/10.1016/j.oraloncology.2014.05.004 CrossRefPubMedPubMedCentral

25.

Jordan RC, Lingen MW, Perez-Ordonez B, He X, Pickard R, Koluder M, Jiang B, Wakely P, Xiao W, Gillison ML (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36(7):945–954. https://doi.org/10.1097/PAS.0b013e318253a2d1 CrossRefPubMed

26.

El-Naggar AK, Westra WH (2012) p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck 34(4):459–461. https://doi.org/10.1002/hed.21974 CrossRefPubMed

27.

Fischer CA, Kampmann M, Zlobec I, Green E, Tornillo L, Lugli A, Wolfensberger M, Terracciano LM (2010) p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters. Ann Oncol Off 21(10):1961–1966. https://doi.org/10.1093/annonc/mdq210 CrossRef

28.

Hong AM, Martin A, Armstrong BK, Lee CS, Jones D, Chatfield MD, Zhang M, Harnett G, Clark J, Elliott M, Milross C, Smee R, Corry J, Liu C, Porceddu S, Vaska K, Veness M, Morgan G, Fogarty G, Veivers D, Rees G, Rose B (2013) Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer. Ann Oncol 24(1):215–219. https://doi.org/10.1093/annonc/mds205 CrossRefPubMed

29.

Keane FK, Chen YH, Neville BA, Tishler RB, Schoenfeld JD, Catalano PJ, Margalit DN (2015) Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era. Cancer 121(15):2594–2602. https://doi.org/10.1002/cncr.29402 CrossRefPubMed

30.

Zaravinos A (2014) An updated overview of HPV-associated head and neck carcinomas. Oncotarget 5(12):3956–3969. https://doi.org/10.18632/oncotarget.1934 CrossRefPubMedPubMedCentral

31.

Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS (2010) Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol 2:15. https://doi.org/10.1186/1758-3284-2-15 CrossRefPubMedPubMedCentral

32.

Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121(8):1813–1820. https://doi.org/10.1002/ijc.22851 CrossRefPubMed

33.

Jacobi C, Ayx I, Fritsche K, Piontek G, Hoffmann D, Weirich G, Knopf A (2015) Potential impact of human papilloma virus on survival of basaloid squamous carcinoma of the head and neck. Oncotarget 6(5):3462–3470. https://doi.org/10.18632/oncotarget.3062 CrossRefPubMed

34.

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35. https://doi.org/10.1056/NEJMoa0912217 CrossRefPubMedPubMedCentral

35.

Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100(4):261–269. https://doi.org/10.1093/jnci/djn011 CrossRefPubMed

36.

Baumeister P, Rauch J, Jacobi C, Kisser U, Betz C, Becker S, Reiter M (2016) Impact of comorbidity and anemia in patients with oropharyngeal cancer primarily treated with surgery in the human papillomavirus era. Head Neck. https://doi.org/10.1002/hed.24528 PubMed

37.

Sayed SI, Sharma S, Rane P, Vaishampayan S, Talole S, Chaturvedi P, Chaukar D, Deshmukh A, Agarwal JP, D’Cruz AK (2013) Can metastatic lymph node ratio (LNR) predict survival in oral cavity cancer patients? J Surgical Oncol 108(4):256–263. https://doi.org/10.1002/jso.23387 CrossRef

38.

Patel SG, Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP, Ebrahimi A, Clark JR, Cernea CR, Brandao SJ, Kreppel M, Zoller J, Fliss D, Fridman E, Bachar G, Shpitzer T, Bolzoni VA, Patel PR, Jonnalagadda S, Robbins KT, Shah JP, Gil Z, International Consortium for Outcome Research in H, Neck C (2013) Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research. Br J Cancer 109(8):2087–2095. https://doi.org/10.1038/bjc.2013.570 CrossRefPubMedPubMedCentral

39.

Wang YL, Feng SH, Zhu J, Zhu GP, Li DS, Wang Y, Zhu YX, Sun GH, Ji QH (2013) Impact of lymph node ratio on the survival of patients with hypopharyngeal squamous cell carcinoma: a population-based analysis. PloS One 8(2):e56613. https://doi.org/10.1371/journal.pone.0056613 CrossRefPubMedPubMedCentral

40.

Lorincz BB, Langwieder F, Mockelmann N, Sehner S, Knecht R (2016) The impact of surgical technique on neck dissection nodal yield: making a difference. Eur Arch Oto-Rhino-Laryngol. 273 (5):1261–1267. https://doi.org/10.1007/s00405-015-3601-1 CrossRef

41.

Norling R, Therkildsen MH, Bradley PJ, Nielsen MB, von Buchwald C (2013) Nodal yield in selective neck dissection. Acta Oto-Laryngologica 133(9):965–971. https://doi.org/10.3109/00016489.2013.799290 CrossRefPubMed

42.

Friedman M, Lim JW, Dickey W, Tanyeri H, Kirshenbaum GL, Phadke DM, Caldarelli D (1999) Quantification of lymph nodes in selective neck dissection. Laryngoscope 109(3):368–370CrossRefPubMed

43.

Upile T, Jerjes W, Nouraei SA, Singh S, Clarke P, Rhys-Evans P, Hopper C, Howard D, Wright A, Sudhoff H, Fisher C, Sandison A (2007) How we do it: a method of neck dissection for histopathological analysis. BMC Surg 7:21. https://doi.org/10.1186/1471-2482-7-21 CrossRefPubMedPubMedCentral

44.

Feng Z, Qin LZ, Huang X, Li JZ, Su M, Han Z (2015) Nodal yield: is it a prognostic factor for head and neck squamous cell carcinoma? J Oral Maxillofacial Surg 73(9):1851–1859. https://doi.org/10.1016/j.joms.2015.03.027 CrossRef

Title: Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status
Authors: Christian Jacobi
Josepha Rauch
Jan Hagemann
Thomas Lautz
Maximilian Reiter
Philipp Baumeister
Publication date: 01-02-2018
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Oto-Rhino-Laryngology / Issue 2/2018
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-017-4833-z

At a glance: The STEP trials

Springer Medicine

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status

Abstract

Objective

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2018

Prosthetic supply of facial defects: long-term experience and retrospective analysis on 99 patients

An evaluation of G-protein coupled membrane estrogen receptor-1 level in stuttering

Epithelial separation theory for post-tonsillectomy secondary hemorrhage: evidence in a mouse model and potential heparin-binding epidermal growth factor-like growth factor therapy

Safety of intranasal corticosteroid sprays during pregnancy: an updated review

Risk factors for intraoperative bradycardia during ear, nose, throat and maxillofacial surgery

Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases