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Journal of Cancer Research and Clinical Oncology

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Open Access 01-10-2016 | Original Article – Clinical Oncology

Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients

Authors: Géraldine Descamps, Yasemin Karaca, Jérôme R Lechien, Nadège Kindt, Christine Decaestecker, Myriam Remmelink, Denis Larsimont, Guy Andry, Samantha Hassid, Alexandra Rodriguez, Mohammad Khalife, Fabrice Journe, Sven Saussez

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2016

Abstract

Purpose

Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers.

Methods

Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan–Meier analysis and both univariate and multivariate Cox regression.

Results

Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001).

Conclusion

The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status.

Fact Sheets by Population. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed 25 Mar 2016

Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35. doi:10.1056/NEJMoa0912217 CrossRefPubMedPubMedCentral

Arnson Y, Shoenfeld Y, Amital H (2010) Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun 34:J258–J265. doi:10.1016/j.jaut.2009.12.003 CrossRefPubMed

Bagnardi V, Rota M, Botteri E et al (2015) Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 112:580–593. doi:10.1038/bjc.2014.579 CrossRefPubMed

Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578. doi:10.1056/NEJMoa053422 CrossRefPubMed

Browman GP, Wong G, Hodson I et al (1993) Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328:159–163. doi:10.1056/NEJM199301213280302 CrossRefPubMed

Chen AM, Chen LM, Vaughan A et al (2011) Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome. Int J Radiat Oncol Biol Phys 79:414–419. doi:10.1016/j.ijrobp.2009.10.050 CrossRefPubMed

Chung Y-L, Lee M-Y, Horng C-F et al (2009) Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone. Head Neck 31:9–20. doi:10.1002/hed.20913 CrossRefPubMed

D’Souza G, Kreimer AR, Viscidi R et al (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944–1956. doi:10.1056/NEJMoa065497 CrossRefPubMed

de Jong MC, Pramana J, Knegjens JL et al (2010) HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors. Radiother Oncol J Eur Soc Ther Radiol Oncol 95:365–370. doi:10.1016/j.radonc.2010.02.001 CrossRef

Depuydt CE, Benoy IH, Bailleul EJ et al (2006) Improved endocervical sampling and HPV viral load detection by Cervex-Brush Combi. Cytopathol Off J Br Soc Clin Cytol 17:374–381. doi:10.1111/j.1365-2303.2006.00386.x CrossRef

Depuydt CE, Boulet GV, Horvath CJ et al (2007) Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types. J Cell Mol Med 11:881–891. doi:10.1111/j.1582-4934.2007.00073.x CrossRefPubMedPubMedCentral

Dikshit RP, Boffetta P, Bouchardy C et al (2005) Lifestyle habits as prognostic factors in survival of laryngeal and hypopharyngeal cancer: a multicentric European study. Int J Cancer 117:992–995. doi:10.1002/ijc.21244 CrossRefPubMed

Doll R, Peto R, Boreham J, Sutherland I (2004) Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 328:1519. doi:10.1136/bmj.38142.554479.AE CrossRefPubMedPubMedCentral

Duffy SA, Ronis DL, McLean S et al (2009) Pretreatment health behaviors predict survival among patients with head and neck squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 27:1969–1975. doi:10.1200/JCO.2008.18.2188 CrossRef

Duray A, Descamps G, Decaestecker C et al (2012) Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma. The Laryngoscope 122:1558–1565. doi:10.1002/lary.23298 CrossRefPubMed

Duray A, Descamps G, Decaestecker C et al (2013) Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas. Oncol Rep 30:371–376. doi:10.3892/or.2013.2415 PubMed

Fakhry C, Gillison ML (2006) Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol Off J Am Soc Clin Oncol 24:2606–2611. doi:10.1200/JCO.2006.06.1291 CrossRef

Fakhry C, Westra WH, Li S et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269. doi:10.1093/jnci/djn011 CrossRefPubMed

Fakhry C, Zhang Q, Nguyen-Tan PF et al (2014) Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 32:3365–3373. doi:10.1200/JCO.2014.55.1937 CrossRef

Fallai C, Perrone F, Licitra L et al (2009) Oropharyngeal squamous cell carcinoma treated with radiotherapy or radiochemotherapy: prognostic role of TP53 and HPV status. Int J Radiat Oncol Biol Phys 75:1053–1059. doi:10.1016/j.ijrobp.2008.12.088 CrossRefPubMed

Flavill E, Fang YV, Miles B et al (2014) Induction chemotherapy followed by concurrent chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma with HPV and P16 testing. Ann Otol Rhinol Laryngol 123:365–373. doi:10.1177/0003489414526685 CrossRefPubMed

Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098. doi:10.1056/NEJMoa031317 CrossRefPubMed

Gama RR, Carvalho AL, Filho AL et al (2016) Detection of human papillomavirus in laryngeal squamous cell carcinoma: systematic review and meta-analysis. Laryngoscope 126:885–893. doi:10.1002/lary.25738 CrossRefPubMed

Gillison ML, Zhang Q, Jordan R et al (2012) Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol Off J Am Soc Clin Oncol 30:2102–2111. doi:10.1200/JCO.2011.38.4099 CrossRef

Giskes K, Kunst AE, Benach J et al (2005) Trends in smoking behaviour between 1985 and 2000 in nine European countries by education. J Epidemiol Community Health 59:395–401. doi:10.1136/jech.2004.025684 CrossRefPubMedPubMedCentral

Gritz ER, Dresler C, Sarna L (2005) Smoking, the missing drug interaction in clinical trials: ignoring the obvious. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 14:2287–2293. doi:10.1158/1055-9965.EPI-05-0224 CrossRef

Hafkamp HC, Manni JJ, Haesevoets A et al (2008) Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer 122:2656–2664. doi:10.1002/ijc.23458 CrossRefPubMed

Hasegawa M, Maeda H, Deng Z et al (2014) Prediction of concurrent chemoradiotherapy outcome in advanced oropharyngeal cancer. Int J Oncol 45:1017–1026. doi:10.3892/ijo.2014.2504 PubMedPubMedCentral

Hilgert E, Bergmann C, Fichtner A et al (2009) Tobacco abuse relates to significantly reduced survival of patients with oropharyngeal carcinomas. Eur J Cancer Prev Off J Eur Cancer Prev Organ ECP 18:120–126. doi:10.1097/CEJ.0b013e32831012a4 CrossRef

Hoff CM, Grau C, Overgaard J (2012) Effect of smoking on oxygen delivery and outcome in patients treated with radiotherapy for head and neck squamous cell carcinoma–a prospective study. Radiother Oncol J Eur Soc Ther Radiol Oncol 103:38–44. doi:10.1016/j.radonc.2012.01.011 CrossRef

Hong AM, Dobbins TA, Lee CS et al (2010) Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer 103:1510–1517. doi:10.1038/sj.bjc.6605944 CrossRefPubMedPubMedCentral

Hu M, Ampil F, Clark C et al (2012) Comorbid predictors of poor response to chemoradiotherapy for laryngeal squamous cell carcinoma. The Laryngoscope 122:565–571. doi:10.1002/lary.22489 CrossRefPubMed

Hu Z, Zhu D, Wang W et al (2015) Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet 47:158–163. doi:10.1038/ng.3178 CrossRefPubMed

Hutcheson KA, Lewin JS (2012) Functional outcomes after chemoradiotherapy of laryngeal and pharyngeal cancers. Curr Oncol Rep 14:158–165. doi:10.1007/s11912-012-0216-1 CrossRefPubMedPubMedCentral

Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M (2012) Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol 6(Suppl 1):S104–S120. doi:10.1007/s12105-012-0368-1 CrossRefPubMed

Kumar B, Cordell KG, Lee JS et al (2007) Response to therapy and outcomes in oropharyngeal cancer are associated with biomarkers including human papillomavirus, epidermal growth factor receptor, gender, and smoking. Int J Radiat Oncol Biol Phys 69:S109–S111. doi:10.1016/j.ijrobp.2007.05.072 CrossRefPubMedPubMedCentral

Kumar B, Cordell KG, Lee JS et al (2008) EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol Off J Am Soc Clin Oncol 26:3128–3137. doi:10.1200/JCO.2007.12.7662 CrossRef

Lazarus CL (2009) Effects of chemoradiotherapy on voice and swallowing. Curr Opin Otolaryngol Head Neck Surg 17:172–178. doi:10.1097/MOO.0b013e32832af12f CrossRefPubMedPubMedCentral

Lee L-A, Huang C-G, Liao C-T et al (2012) Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival. PLoS ONE 7:e40767. doi:10.1371/journal.pone.0040767 CrossRefPubMedPubMedCentral

Lill C, Kornek G, Bachtiary B et al (2011) Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced. Wien Klin Wochenschr 123:215–221. doi:10.1007/s00508-011-1553-z CrossRefPubMed

Lin BM, Wang H, D’Souza G et al (2013) Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer 119:3462–3471. doi:10.1002/cncr.28250 CrossRefPubMedPubMedCentral

Maxwell JH, Kumar B, Feng FY et al (2010) Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res Off J Am Assoc Cancer Res 16:1226–1235. doi:10.1158/1078-0432.CCR-09-2350 CrossRef

Nichols AC, Faquin WC, Westra WH et al (2009) HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol-Head Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg 140:228–234. doi:10.1016/j.otohns.2008.11.025 CrossRef

Nygård M, Aagnes B, Bray F et al (2012) Population-based evidence of increased survival in human papillomavirus-related head and neck cancer. Eur J Cancer Oxf Engl 48:1341–1346. doi:10.1016/j.ejca.2012.03.014 CrossRef

Park SM, Lim MK, Shin SA, Yun YH (2006) Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study. J Clin Oncol Off J Am Soc Clin Oncol 24:5017–5024. doi:10.1200/JCO.2006.07.0243 CrossRef

Rischin D, Young RJ, Fisher R et al (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol Off J Am Soc Clin Oncol 28:4142–4148. doi:10.1200/JCO.2010.29.2904 CrossRef

Rosenquist K, Wennerberg J, Annertz K et al (2007) Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors. Acta Otolaryngol (Stockh) 127:980–987. doi:10.1080/00016480601110162 CrossRef

Rosenthal DI, Harari PM, Giralt J et al (2015) Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol Off J Am Soc Clin Oncol. doi:10.1200/JCO.2015.62.5970

Sawicka M, Pawlikowski J, Wilson S et al (2013) The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding. PLoS ONE 8:e53313. doi:10.1371/journal.pone.0053313 CrossRefPubMedPubMedCentral

Sharp L, McDevitt J, Carsin A-E et al (2014) Smoking at diagnosis is an independent prognostic factor for cancer-specific survival in head and neck cancer: findings from a large, population-based study. Cancer Epidemiol Biomark Prev 23:2579–2590. doi:10.1158/1055-9965.EPI-14-0311 CrossRef

Smeets SJ, Hesselink AT, Speel E-JM et al (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472. doi:10.1002/ijc.22980 CrossRefPubMed

Sturgis EM, Cinciripini PM (2007) Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110:1429–1435. doi:10.1002/cncr.22963 CrossRefPubMed

Tinhofer I, Jöhrens K, Keilholz U et al (2015) Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence. Eur J Cancer Oxf Engl 51:514–521. doi:10.1016/j.ejca.2014.12.018 CrossRef

Tribius S, Hoffmann AS, Bastrop S et al (2012) HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome. Oral Oncol 48:1178–1184. doi:10.1016/j.oraloncology.2012.05.022 CrossRefPubMed

Trotti A, Bellm LA, Epstein JB et al (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol J Eur Soc Ther Radiol Oncol 66:253–262CrossRef

Title: Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients
Authors: Géraldine Descamps
Yasemin Karaca
Jérôme R Lechien
Nadège Kindt
Christine Decaestecker
Myriam Remmelink
Denis Larsimont
Guy Andry
Samantha Hassid
Alexandra Rodriguez
Mohammad Khalife
Fabrice Journe
Sven Saussez
Publication date: 01-10-2016
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2016
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2203-7

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Abstract

Purpose

Methods

Results

Conclusion

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