Effects of tobacco abuse on major chromosomal instability in human papilloma virus 16-positive oropharyngeal squamous cell carcinoma

Villepelet,Aude; Hugonin,Sylvain; Atallah,Sarah; Job,Bastien; Baujat,Bertrand; Lacau St. Guily,Jean; Lacave,Roger

doi:10.3892/ijo.2019.4826

Effects of tobacco abuse on major chromosomal instability in human papilloma virus 16-positive oropharyngeal squamous cell carcinoma

Authors:
- Aude Villepelet
- Sylvain Hugonin
- Sarah Atallah
- Bastien Job
- Bertrand Baujat
- Jean Lacau St. Guily
- Roger Lacave
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Affiliations: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Otolaryngology-Head and Neck Surgery, Tenon Hospital, 75020 Paris, France, Assistance Publique-Hôpitaux de Paris (AP-HP), Tumors Genomic Unit, Tenon Hospital, 75020 Paris, France, INSERM US23, Gustave Roussy Cancer Campus, 94805 Villejuif, France, Faculty of Medicine, Sorbonne University, GRC10, 75013 Paris, France
Published online on: June 18, 2019 https://doi.org/10.3892/ijo.2019.4826
Pages: 527-535

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Abstract

A substantial number of patients with oropharyngeal squamous cell carcinoma (OPSCC) have two oncogenic risk factors: Human papilloma virus (HPV) infection and tobacco use. These factors can be competitive or synergistic at the chromosomal and genomic levels, with strong prognostic and therapeutic implications. HPV16 has been shown in vitro to be a high‑risk HPV that induces low rates of chromosomal copy number alterations. However, chromosomal instability can be increased by smoking. Evaluating chromosomal instability in HPV‑positive patients according to their smoking status is therefore critical for assessing the prognosis and therapeutic impact. The aim of this study was to assess chromosomal instability in patients with HPV‑positive OPSCC according to smoking status. Chromosomal instability was investigated with array‑based comparative genomic hybridization (aCGH) in 50 patients with OPSCC. Differences in chromosomal alterations were examined according to the HPV and smoking status of the patients. HPV‑positive tumors (24/26 were HPV16‑positive) had fewer genomic aberrations (P=0.0082) and fewer breakpoints (P=0.048) than HPV‑negative tumors. We confirmed the association between HPV‑positive OPSCC and chromosomal losses at 11q. We verified the association between HPV‑negative OPSCC and losses at 3p and 9p and gains at 7q and 11q13. In the patients with OPSCC who were HPV‑positive, the total number of chromosomal aberrations per tumor was significantly higher in the group of patients who were smokers (P=0.003). However, the cytobands did not differ significantly according to the smoking status. On the whole, the data of this study may help to improve the stratification of HPV‑positive OPSCC patients and must be supplemented by next‑generation sequencing studies in order to describe the mutational and transcriptomic profiles of such patients according to smoking status.

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1	Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Møller B, Pukkala E, Schiller JT, Youngman L, et al: Human papil-lomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 344:1125–1131. 2001. View Article : Google Scholar : PubMed/NCBI
2	Gillison ML and Shah KV: Human papillomavirus-associated head and neck squamous cell carcinoma: Mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol. 13:183–188. 2001. View Article : Google Scholar : PubMed/NCBI
3	Kreimer AR, Clifford GM, Boyle P and Franceschi S: Human papillomavirus types in head and neck squamous cell carcinomas worldwide: A systematic review. Cancer Epidemiol Biomarkers Prev. 14:467–475. 2005. View Article : Google Scholar : PubMed/NCBI
4	Moody CA and Laimins LA: Human papillomavirus oncoproteins: Pathways to transformation. Nat Rev Cancer. 10:550–560. 2010. View Article : Google Scholar : PubMed/NCBI
5	Leemans CR, Snijders PJF and Brakenhoff RH: The molecular landscape of head and neck cancer. Nat Rev Cancer. 18:269–282. 2018. View Article : Google Scholar : PubMed/NCBI
6	Lacau St Guily J, Rousseau A, Baujat B, Périé S, Schultz P, Barry B, Dufour X, Malard O, Pretet JL, Clavel C, et al Papillophar Group: Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study. Oral Oncol. 67:29–36. 2017. View Article : Google Scholar : PubMed/NCBI
7	Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, et al: Human papillomavirus and survival of patients with oropha-ryngeal cancer. N Engl J Med. 363:24–35. 2010. View Article : Google Scholar : PubMed/NCBI
8	Gillison ML and Restighini C: Anticipation of the impact of human papillomavirus on clinical decision making for the head and neck cancer patient. Hematol Oncol Clin North Am. 29:1045–1060. 2015. View Article : Google Scholar : PubMed/NCBI
9	Posner MR, Lorch JH, Goloubeva O, Tan M, Schumaker LM, Sarlis NJ, Haddad RI and Cullen KJ: Survival and human papillo-mavirus in oropharynx cancer in TAX 324: A subset analysis from an international phase III trial. Ann Oncol. 22:1071–1077. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ragin CC and Taioli E: Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta-analysis. Int J Cancer. 121:1813–1820. 2007. View Article : Google Scholar : PubMed/NCBI
11	Wittekindt C, Wagner S, Mayer CS and Klussmann JP: Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer. GMS Curr Top Otorhinolaryngol Head Neck Surg. 11:Doc092012.
12	Hong A, Zhang X, Jones D, Veillard AS, Zhang M, Martin A, Lyons JG, Lee CS and Rose B: Relationships between p53 mutation, HPV status and outcome in oropharyngeal squamous cell carcinoma. Radiother Oncol. 118:342–349. 2016. View Article : Google Scholar : PubMed/NCBI
13	Combes JD, Chen AA and Franceschi S: Prevalence of human papillomavirus in cancer of the oropharynx by gender. Cancer Epidemiol Biomarkers Prev. 23:2954–2958. 2014. View Article : Google Scholar : PubMed/NCBI
14	Pytynia KB, Dahlstrom KR and Sturgis EM: Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol. 50:380–386. 2014. View Article : Google Scholar : PubMed/NCBI
15	Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, Ringash J, Bayley A, Kim J, Hope A, et al: 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. 33:836–845. 2015. View Article : Google Scholar : PubMed/NCBI
16	Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, Wolf GT, Prince ME, Moyer JS, Teknos TN, et al: Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 16:1226–1235. 2010. View Article : Google Scholar : PubMed/NCBI
17	Hafkamp HC, Manni JJ, Haesevoets A, Voogd AC, Schepers M, Bot FJ, Hopman AH, Ramaekers FC and Speel EJ: Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer. 122:2656–2664. 2008. View Article : Google Scholar : PubMed/NCBI
18	Weller MA, Ward MC, Berriochoa C, Reddy CA, Trosman S, Greskovich JF, Nwizu TI, Burkey BB, Adelstein DJ and Koyfman SA: Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer. Head Neck. 39:940–946. 2017. View Article : Google Scholar : PubMed/NCBI
19	Smith EM, Rubenstein LM, Haugen TH, Hamsikova E and Turek LP: Tobacco and alcohol use increases the risk of both HPV-associated and HPV-independent head and neck cancers. Cancer Causes Control. 21:1369–1378. 2010. View Article : Google Scholar : PubMed/NCBI
20	Sinha P, Logan HL and Mendenhall WM: Human papillomavirus, smoking, and head and neck cancer. Am J Otolaryngol. 33:130–136. 2012. View Article : Google Scholar
21	Duensing S and Münger K: The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res. 62:7075–7082. 2002.PubMed/NCBI
22	Duensing S and Münger K: Mechanisms of genomic instability in human cancer: Insights from studies with human papillomavirus oncoproteins. Int J Cancer. 109:157–162. 2004. View Article : Google Scholar : PubMed/NCBI
23	Schütze DM, Krijgsman O, Snijders PJ, Ylstra B, Weischenfeldt J, Mardin BR, Stütz AM, Korbel JO, de Winter JP, Meijer CJ, et al: Immortalization capacity of HPV types is inversely related to chromosomal instability. Oncotarget. 7:37608–37621. 2016. View Article : Google Scholar : PubMed/NCBI
24	Mooren JJ, Kremer B, Claessen SM, Voogd AC, Bot FJ, Peter Klussmann J, Huebbers CU, Hopman AH, Ramaekers FC and Speel EJ: Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis. Int J Cancer. 132:1781–1789. 2013. View Article : Google Scholar
25	Morrison LE, Jacobson KK, Friedman M, Schroeder JW and Coon JS: Aberrant EGFR and chromosome 7 associate with outcome in laryngeal cancer. Laryngoscope. 115:1212–1218. 2005. View Article : Google Scholar : PubMed/NCBI
26	Veltman JA, Bot FJ, Huynen FC, Ramaekers FC, Manni JJ and Hopman AH: Chromosome instability as an indicator of malignant progression in laryngeal mucosa. J Clin Oncol. 18:1644–1651. 2000. View Article : Google Scholar : PubMed/NCBI
27	Dahlgren L, Mellin H, Wangsa D, Heselmeyer-Haddad K, Björnestål L, Lindholm J, Munck-Wikland E, Auer G, Ried T and Dalianis T: Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and -negative tumors. Int J Cancer. 107:244–249. 2003. View Article : Google Scholar : PubMed/NCBI
28	Klussmann JP, Mooren JJ, Lehnen M, Claessen SM, Stenner M, Huebbers CU, Weissenborn SJ, Wedemeyer I, Preuss SF, Straetmans JM, et al: Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res. 15:1779–1786. 2009. View Article : Google Scholar : PubMed/NCBI
29	Jung AC, Briolat J, Millon R, de Reyniès A, Rickman D, Thomas E, Abecassis J, Clavel C and Wasylyk B: Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma. Int J Cancer. 126:1882–1894. 2010. View Article : Google Scholar
30	Brierley JD, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours. 8th edition. Wiley-Blackwell; New Jersey: pp. p2722017
31	Picard F, Lebarbier E, Hoebeke M, Rigaill G, Thiam B and Robin S: Joint segmentation, calling, and normalization of multiple CGH profiles. Biostatistics. 12:413–428. 2011. View Article : Google Scholar : PubMed/NCBI
32	Olshen AB, Venkatraman ES, Lucito R and Wigler M: Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 5:557–572. 2004. View Article : Google Scholar : PubMed/NCBI
33	Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R and Getz G: GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 12:R412011. View Article : Google Scholar : PubMed/NCBI
34	Anantharaman D, Muller DC, Lagiou P, Ahrens W, Holcátová I, Merletti F, Kjærheim K, Polesel J, Simonato L, Canova C, et al: Combined effects of smoking and HPV16 in oropharyngeal cancer. Int J Epidemiol. 45:752–761. 2016. View Article : Google Scholar : PubMed/NCBI
35	Chaturvedi AK, D'Souza G, Gillison ML and Katki HA: Burden of HPV-positive oropharynx cancers among ever and never smokers in the U.S. population. Oral Oncol. 60:61–67. 2016. View Article : Google Scholar : PubMed/NCBI
36	Zevallos J, Yim E, Brennan P, Liu AY, Taylor JM, Weissler M, Anantharaman D, Abedi-Ardekani B, Olshan AF and Hayes NN: Molecular profile of human papillomavirus-positive oropharyngeal squamous cell carcinoma stratified by smoking status. Int J Radiat Oncol Biol Phys. 94:8642016. View Article : Google Scholar
37	Mirghani H, Lacroix L, Rossoni C, Sun R, Aupérin A, Casiraghi O, Villepelet A, Lacave R, Faucher G, Marty V, et al: Does smoking alter the mutation profile of human papillomavirus-driven head and neck cancers? Eur J Cancer. 94:61–69. 2018. View Article : Google Scholar : PubMed/NCBI
38	Grønhøj C, Jensen DH, Agander T, Kiss K, Høgdall E, Specht L, Bagger FO, Nielsen FC and von Buchwald C: Deep sequencing of human papillomavirus positive loco-regionally advanced oropha-ryngeal squamous cell carcinomas reveals novel mutational signature. BMC Cancer. 18:6402018. View Article : Google Scholar
39	Masuda A and Takahashi T: Chromosome instability in human lung cancers: Possible underlying mechanisms and potential consequences in the pathogenesis. Oncogene. 21:6884–6897. 2002. View Article : Google Scholar : PubMed/NCBI
40	Hecht SS: Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 3:733–744. 2003. View Article : Google Scholar : PubMed/NCBI
41	Hecht SS: Carcinogenicity studies of inhaled cigarette smoke in laboratory animals: Old and new. Carcinogenesis. 26:1488–1492. 2005. View Article : Google Scholar : PubMed/NCBI
42	Herzog CR, Desai D and Amin S: Array CGH analysis reveals chromosomal aberrations in mouse lung adenocarcinomas induced by the human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone. Biochem Biophys Res Commun. 341:856–863. 2006. View Article : Google Scholar : PubMed/NCBI
43	Saletta F, Matullo G, Manuguerra M, Arena S, Bardelli A and Vineis P: Exposure to the tobacco smoke constituent 4-aminobi-phenyl induces chromosomal instability in human cancer cells. Cancer Res. 67:7088–7094. 2007. View Article : Google Scholar : PubMed/NCBI
44	Hays LE, Zodrow DM, Yates JE, Deffebach ME, Jacoby DB, Olson SB, Pankow JF and Bagby GC: Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. Br J Cancer. 98:1653–1661. 2008. View Article : Google Scholar : PubMed/NCBI