Abstract
Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 were obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988 to 1997 as the pre-HPV cohort (N = 752), and 1998–2007 as the HPV-predominant cohort (N = 2,755). Comparing the two cohorts, Kaplan–Meier 5-year overall survival (OS) for tonsil SCC improved from 54.0 to 74.3 % (p < 0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9 % (p < 0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7 %, p < 0.0001), two to three (54.2 vs. 75.9 %, p < 0.0001), four to eight (40.3 vs. 68.9 %, p < 0.0001), and greater than eight positive nodes (25.5 vs. 41.9 %, p < 0.0001). While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from “classical” OPC, with unique prognostic features.
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Wisnivesky JP, Arciniega J, Mhango G, Mandeli J, Halm EA (2010) Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer. Thorax. doi:10.1136/thx.2010.148601
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. doi:10.1002/cncr.24631
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. doi:10.1002/hed.21114
Shrime MG, Ma C, Gullane PJ, Gilbert RW, Irish JC, Brown DH, Goldstein DP (2009) Impact of nodal ratio on survival in squamous cell carcinoma of the oral cavity. Head Neck 31(9):1129–1136. doi:10.1002/hed.21073
Olsen KD, Caruso M, Foote RL, Stanley RJ, Lewis JE, Buskirk SJ, Frassica DA, DeSanto LW, O’Fallon WM, Hoverman VR (1994) Primary head and neck cancer. Histopathologic predictors of recurrence after neck dissection in patients with lymph node involvement. Arch Otolaryngol Head Neck Surg 120(12):1370–1374
Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1993) Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer 71(2):452–456
Leemans CR, Tiwari R, Nauta JJP, Vanderwaal I, Snow GB (1994) Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 73(1):187–190
Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J (1994) Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg 168(5):494–498
Hammarstedt L, Lindquist D, Dahlstrand H, Romanitan M, Dahlgren LO, Joneberg J, Creson N, Lindholm J, Ye W, Dalianis T, Munck-Wikland E (2006) Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer 119(11):2620–2623. doi:10.1002/ijc.22177
D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356(19):1944–1956. doi:10.1056/NEJMoa065497
Ernster JA, Sciotto CG, O’Brien MM, Finch JL, Robinson LJ, Willson T, Mathews M (2007) Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. The Laryngoscope 117(12):2115–2128. doi:10.1097/MLG.0b013e31813e5fbb
Chung CH, Gillison ML (2009) Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res 15(22):6758–6762. doi:10.1158/1078-0432.CCR-09-0784
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. JNCI J Natl Cancer Inst 100(4):261–269. doi:10.1093/jnci/djn011
Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM (2001) Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 92(4):805–813
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân 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. doi:10.1056/NEJMoa0912217
Chaturvedi AK, 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 (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301 (Epub 2011 Oct 4293)
National Cancer Institute (2011) About the SEER Program. http://seer.cancer.gov/about/. Accessed February 25 2011
El-Mofty SK, Lu DW (2003) Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients––a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 27(11):1463–1470. doi:10.1097/00000478-200311000-00010
Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME, Wu XC, Chaturvedi AK, Kawaoka K (2008) Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998–2003. Cancer 113(10):2901–2909. doi:10.1002/cncr.23745
Bernier J, Cooper J, Pajak T, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin E, Jacobs J, Jassem J, Ang K, Lefebvre J (2005) Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501). Head Neck 27(10):843–850
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This work was supported by the Doris Duke Charitable Foundation.
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Vila, P.M., Stucken, C.L., Morris, L.G.T. et al. Reduced impact of nodal metastases as a prognostic factor for tonsil cancer in the HPV era. Eur Arch Otorhinolaryngol 271, 2523–2529 (2014). https://doi.org/10.1007/s00405-013-2796-2
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DOI: https://doi.org/10.1007/s00405-013-2796-2