Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas

Duray,Anaëlle; Descamps,Géraldine; Decaestecker,Christine; Sirtaine,Nicolas; Gilles,André; Khalifé,Mohamad; Chantrain,Gilbert; Depuydt,Christophe E.; Delvenne,Philippe; Saussez,Sven

doi:10.3892/or.2013.2415

Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas

Authors:
- Anaëlle Duray
- Géraldine Descamps
- Christine Decaestecker
- Nicolas Sirtaine
- André Gilles
- Mohamad Khalifé
- Gilbert Chantrain
- Christophe E. Depuydt
- Philippe Delvenne
- Sven Saussez
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Affiliations: Laboratory of Anatomy, Faculty of Medicine and Pharmacy, University of Mons, Mons, Belgium, Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium, Department of Pathology, Faculty of Medicine, Institut Bordet, Free University of Brussels, Brussels, Belgium, Department of Pathology, RHMS Baudour, Mons, Belgium, Department of Oto-Rhino-Laryngology, CHU Saint-Pierre, Free University of Brussels, Brussels, Belgium, Laboratory for Clinical Pathology and Molecular Biology (LaboLokeren, Campus Riatol), Antwerp, Belgium, Department of Pathology, CHU Sart-Tilman, University of Liège, Liège, Belgium
Published online on: April 22, 2013 https://doi.org/10.3892/or.2013.2415
Pages: 371-376

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Abstract

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.

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1	World Health Organization. International Agency for Research on Cancer. Globocan. 2008, Available from: http://globocan.iarc.fr/.
2	Grandis JR, Pietenpol JA, Greenberger JS, Pelroy RA and Mohla S: Head and neck cancer: meeting summary and research opportunities. Cancer Res. 64:8126–8129. 2004. View Article : Google Scholar : PubMed/NCBI
3	Shah JP and Patel SG: Head and Neck Surgery and Oncology. 3rd edition. Mosby; New York: pp. 232–236. 352. 2003
4	Forastiere AA and Trotti A: Radiotherapy and concurrent chemotherapy: a strategy that improves locoregional control and survival in oropharyngeal cancer. J Natl Cancer Inst. 91:2065–2066. 1999. View Article : Google Scholar : PubMed/NCBI
5	Denis F, Garaud P, Bardet E, et al: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 22:69–76. 2004. View Article : Google Scholar
6	Stenson KM, Kunnavakkam R, Cohen EE, et al: Chemoradiation for patients with advanced oral cavity cancer. Laryngoscope. 120:93–99. 2010.PubMed/NCBI
7	Milano MT, Vokes EE, Kao J, et al: Intensity-modulated radiation therapy in advanced head and neck patients treated with intensive chemoradiotherapy: preliminary experience and future directions. Int J Oncol. 28:1141–1151. 2006.
8	Hu M, Ampil F, Clark C, Sonavane K, Caldito G and Nathan CA: Comorbid predictors of poor response to chemoradiotherapy for laryngeal squamous cell carcinoma. Laryngoscope. 122:565–571. 2012. View Article : Google Scholar : PubMed/NCBI
9	Sturgis EM and Cinciripini PM: Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 110:1429–1435. 2007. View Article : Google Scholar : PubMed/NCBI
10	Dahlstrand H, Nasman A, Romanitan M, Lindquist D, Ramqvist T and Dalianis T: Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer. Anticancer Res. 28:1133–1138. 2008.PubMed/NCBI
11	Reimers N, Kasper HU, Weissenborn SJ, et al: Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer. 120:1731–1738. 2007. View Article : Google Scholar : PubMed/NCBI
12	Kumar B, Cordell KG, Lee JS, et al: 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. 69:109–111. 2007. View Article : Google Scholar
13	Rischin D, Young RJ, Fisher R, et al: Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 28:4142–4148. 2010. View Article : Google Scholar : PubMed/NCBI
14	Lill C, Kornek G, Bachtiary B, et al: Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced. Wien Klin Wochenschr. 123:215–221. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hong AM, Dobbins TA, Lee CS, et al: Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 103:1510–1517. 2010. View Article : Google Scholar : PubMed/NCBI
16	Sedaghat AR, Zhang Z, Begum S, et al: Prognostic significance of human papillomavirus in oropharyngeal squamous cell carcinomas. Laryngoscope. 119:1542–1549. 2009. View Article : Google Scholar : PubMed/NCBI
17	Chung YL, Lee MY, Horng CF, et al: Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone. Head Neck. 31:9–20. 2009. View Article : Google Scholar : PubMed/NCBI
18	Nichols AC, Faquin WC, Westra WH, et al: HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. 140:228–234. 2009. View Article : Google Scholar : PubMed/NCBI
19	de Jong MC, Pramana J, Knegjens JL, et al: HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors. Radiother Oncol. 95:365–370. 2010.PubMed/NCBI
20	Fallai C, Perrone F, Licitra L, et al: 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. 2009. View Article : Google Scholar : PubMed/NCBI
21	Pim D, Collins M and Banks L: Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. Oncogene. 7:27–32. 1992.PubMed/NCBI
22	Depuydt CE, Benoy IH, Bailleul EJ, Vandepitte J, Vereecken AJ and Bogers JJ: Improved endocervical sampling and HPV viral load detection by Cervex-Brush Combi. Cytopathology. 17:374–381. 2006. View Article : Google Scholar : PubMed/NCBI
23	Depuydt CE, Boulet GA, Horvath CA, Benoy IH, Vereecken AJ and Bogers JJ: Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types. J Cell Mol Med. 11:881–891. 2007. View Article : Google Scholar
24	Arbyn M, Benoy I, Simoens C, Bogers J, Beutels P and Depuydt C: Prevaccination distribution of human papillomavirus types in women attending at cervical cancer screening in Belgium. Cancer Epidemiol Biomarkers Prev. 18:321–330. 2009. View Article : Google Scholar : PubMed/NCBI
25	Filleul O, Preillon J, Crompot E, Lechien J and Saussez S: Incidence of head and neck cancers in Belgium: comparison with worldwide and French data. Bulletin du Cancer. 98:1173–1183. 2011.
26	Saussez S: Cancer of the upper aero-digestive tract: elevated incidence in Belgium, new risk factors and therapeutic perspectives. Bull Mem Acad R Med Belg. 165:453–461. 2010.PubMed/NCBI
27	Duray A, Descamps G, Decaestecker C, et al: Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma. Laryngoscope. 122:1558–1565. 2012. View Article : Google Scholar : PubMed/NCBI
28	Rosenquist K, Wennerberg J, Annertz K, et al: Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors. Acta Otolaryngol. 127:980–987. 2007. View Article : Google Scholar : PubMed/NCBI
29	Hansson BG, Rosenquist K, Antonsson A, et al: Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta Otolaryngol. 125:1337–1344. 2005. View Article : Google Scholar
30	Clayman GL, Stewart MG, Weber RS, el-Naggar AK and Grimm EA: Human papillomavirus in laryngeal and hypopharyngeal carcinomas. Relationship to survival. Arch Otolaryngol. 120:743–748. 1994. View Article : Google Scholar : PubMed/NCBI
31	Giskes K, Kunst AE, Benach J, et al: Trends in smoking behavior between 1985 and 2000 in nine European countries by education. J Epidemiol Community Health. 59:395–401. 2005. View Article : Google Scholar : PubMed/NCBI
32	Stanley MA: Immune responses to human papillomaviruses. Indian J Med Res. 130:266–276. 2009.PubMed/NCBI
33	Hasan UA, Bates E, Takeshita F, et al: TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16. J Immunol. 178:3186–3197. 2007. View Article : Google Scholar : PubMed/NCBI
34	Lepique AP, Daghastanli KR, Cuccovia IM and Villa LL: HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res. 15:4391–4400. 2009. View Article : Google Scholar : PubMed/NCBI
35	Stanley MA: Immune responses to human papillomavirus. Vaccine. 24:16–22. 2006. View Article : Google Scholar
36	Tung YC, Lin KH, Chu PY, Hsu CC and Kuo WR: Detection of human papillomavirus and Epstein Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction. Kaohsiung J Med Sci. 15:256–262. 1999.PubMed/NCBI
37	Moscicki AB, Hills N, Shiboski S, et al: Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA. 285:2995–3002. 2001. View Article : Google Scholar
38	Kreimer AR, Alberg AJ, Daniel R, et al: Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis. 189:686–698. 2004. View Article : Google Scholar : PubMed/NCBI