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Human papillomavirus in oropharyngeal squamous cell carcinoma in South-Eastern Norway: prevalence, genotype, and survival

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Abstract

The objectives of this study were to assess the prevalence of high-risk human papillomavirus (HR HPV) and survival in all oropharyngeal cancer (OPSCC) patients in a Norwegian population cohort in 2010–2011. Clinical data were retrieved from hospital records. Biopsies from 166 patients were tested for the presence of HR HPV by qualitative polymerase chain reaction (qPCR). p16 immunohistochemistry was performed in 138 cases. Survival was compared between groups of patients with tumors positive for HPV16 and other HR HPV genotypes, and patients with HPV negative tumors. HR HPV was detected in 127 out of 166 cases (77%). HPV16 was the most prevalent genotype (n = 108), followed by HPV33 (n = 12), HPV18 (n = 3), and HPV31/35/56/59 (n = 1). There was a robust and significant association between p16 and HR HPV status. (Chi square 70.8; p < 0.0001). Among p16-positive/HR HPV-positive cases, the distribution of HPV16 and other HR HPV types was not significantly different [91% (88/97) versus 82% (14/17); p = 0.30]. HR HPV-negative patients had reduced overall survival compared to HR HPV-positive patients [hazard ratio 0.30; 95% confidence interval (CI) 0.16–0.56, p < 0.001]. Non-HPV16 HR HPV-positive patients had significantly poorer overall survival than HPV16-positive patients (hazard ratio 0.35; 95% CI 0.14–0.85, p = 0.02). Prevalence of HR HPV in OPSCC in Norway is high, and similar to the level reported in recent years from other countries in Northern Europe and in North America. HPV genoty** may be valuable in future risk-stratification algorithms for treatment of patients with HPV-positive OPSCC.

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References

  1. 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. doi:10.1056/NEJMoa0912217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fakhry C, Psyrri A, Chaturvedhi A (2014) HPV and head and neck cancers: state-of-the-science. Oral Oncol 50(5):353–355. doi:10.1016/j.oraloncology.2014.03.010

    Article  PubMed  Google Scholar 

  3. 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. doi:10.1093/jnci/djn011

    Article  CAS  PubMed  Google Scholar 

  4. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML (2013) Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol Off J Am Soc Clin Oncol 31(36):4550–4559. doi:10.1200/JCO.2013.50.3870

    Article  Google Scholar 

  5. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, **ao 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 Off J Am Soc Clin Oncol 29(32):4294–4301. doi:10.1200/JCO.2011.36.4596

    Article  Google Scholar 

  6. Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparen P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T (2009) Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer (Journal international du cancer) 125(2):362–366. doi:10.1002/ijc.24339

    Article  Google Scholar 

  7. Simard EP, Torre LA, Jemal A (2014) International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol 50(5):387–403. doi:10.1016/j.oraloncology.2014.01.016

    Article  PubMed  Google Scholar 

  8. Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck 35(5):747–755. doi:10.1002/hed.22015

    Article  PubMed  Google Scholar 

  9. Rodrigo JP, Heideman DA, Garcia-Pedrero JM, Fresno MF, Brakenhoff RH, Diaz Molina JP, Snijders PJ, Hermsen MA (2014) Time trends in the prevalence of HPV in oropharyngeal squamous cell carcinomas in northern Spain (1990–2009). Int J Cancer (Journal international du cancer) 134(2):487–492. doi:10.1002/ijc.28355

    Article  Google Scholar 

  10. Nasman A, Nordfors C, Holzhauser S, Vlastos A, Tertipis N, Hammar U, Hammarstedt-Nordenvall L, Marklund L, Munck-Wikland E, Ramqvist T, Bottai M, Dalianis T (2015) Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma? Eur J Cancer (Oxford England: 1950 51(1):55–61. doi:10.1016/j.ejca.2014.10.016

    Article  Google Scholar 

  11. Mork J, Moller B, Dahl T, Bray F (2010) Time trends in pharyngeal cancer incidence in Norway 1981–2005: a subsite analysis based on a reabstraction and recoding of registered cases. Cancer Causes Control CCC 21(9):1397–1405. doi:10.1007/s10552-010-9567-9

    Article  PubMed  Google Scholar 

  12. Goodman MT, Saraiya M, Thompson TD, Steinau M, Hernandez BY, Lynch CF, Lyu CW, Wilkinson EJ, Tucker T, Copeland G, Peters ES, Altekruse S, Unger ER (2015) Human papillomavirus genotype and oropharynx cancer survival in the United States of America. Eur J Cancer (Oxford, England: 1990) 51(18):2759–2767. doi:10.1016/j.ejca.2015.09.005

    Article  Google Scholar 

  13. Mazul AL, Rodriguez-Ormaza N, Taylor JM, Desai DD, Brennan P, Anantharaman D, Gheit T, Tommasino M, Abedi-Ardekani B, Olshan AF, Zevallos JP (2016) Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell carcinoma. Oral Oncol 61:98–103. doi:10.1016/j.oraloncology.2016.08.019

    Article  PubMed  PubMed Central  Google Scholar 

  14. Varier I, Keeley BR, Krupar R, Patsias A, Dong J, Gupta N, Parasher AK, Genden EM, Miles BA, Teng M, Bakst RL, Gupta V, Misiukiewicz KJ, Chiao EY, Scheurer ME, Laban S, Zhang D, Ye F, Cui M, Demicco EG, Posner MR, Sikora AG (2016) Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non-human papillomavirus16 viral subtypes. Head Neck 38(9):1330–1337. doi:10.1002/hed.24442

    Article  PubMed  Google Scholar 

  15. Lindh M, Gorander S, Andersson E, Horal P, Mattsby-Balzer I, Ryd W (2007) Real-time Taqman PCR targeting 14 human papilloma virus types. J Clin Virol Off Publ Pan Am Soc Clin Virol 40(4):321–324. doi:10.1016/j.jcv.2007.09.009

    Article  CAS  Google Scholar 

  16. Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Moller B, Pukkala E, Schiller JT, Youngman L, Lehtinen M, Dillner J (2001) Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344(15):1125–1131. doi:10.1056/NEJM200104123441503

    Article  CAS  PubMed  Google Scholar 

  17. Hannisdal K, Schjolberg A, De Angelis PM, Boysen M, Clausen OP (2010) Human papillomavirus (HPV)-positive tonsillar carcinomas are frequent and have a favourable prognosis in males in Norway. Acta Otolaryngol 130(2):293–299. doi:10.3109/00016480903071377

    Article  CAS  PubMed  Google Scholar 

  18. Garnaes E, Kiss K, Andersen L, Therkildsen MH, Franzmann MB, Filtenborg-Barnkob B, Hoegdall E, Krenk L, Josiassen M, Lajer CB, Specht L, Frederiksen K, Friis-Hansen L, Nielsen FC, Kjaer SK, Norrild B, von Buchwald C (2015) A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000–2010: the largest registry-based study to date. Int J Cancer (Journal international du cancer) 136(9):2196–2203. doi:10.1002/ijc.29254

    Article  CAS  Google Scholar 

  19. Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsague X, Laporte L, Bosch FX, de Sanjose S, Trottier H (2014) HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol 15(12):1319–1331. doi:10.1016/S1470-2045(14)70471-1

    Article  CAS  PubMed  Google Scholar 

  20. IARC (2012) Biological agents. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol 100B. IARC, Lyon, pp 275–276

  21. Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58:295–300

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709–720

    Article  CAS  PubMed  Google Scholar 

  23. O’Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA (2012) Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol 48(12):1191–1201. doi:10.1016/j.oraloncology.2012.06.019

    Article  PubMed  Google Scholar 

  24. Mirghani H, Amen F, Blanchard P, Moreau F, Guigay J, Hartl DM, Lacau St Guily J (2015) Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives. Int J Cancer (Journal international du cancer) 136(7):1494–1503. doi:10.1002/ijc.28847

    Article  CAS  Google Scholar 

  25. Kelly JR, Husain ZA, Burtness B (2016) Treatment de-intensification strategies for head and neck cancer. Eur J Cancer (Oxford, England: 1990) 68:125–133. doi:10.1016/j.ejca.2016.09.006

    Article  Google Scholar 

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Acknowledgements

For statistical support, we are indebted to Leiv Sandvik and Morten Valberg at Oslo Centre for Biostatistics and Epidemiology. Dr. Jan Folkvard Evensen at the Department of Oncology, Oslo University Hospital, provided helpful comments to the manuscript.

Author information

Author notes

  1. Agnes Kathrine Lie

    Present address: Department of Pathology, Kalnes Hospital, Kalnesveien 300, 1714, Grålum, Norway

  2. Lars Erik Sandlie

    Present address: Roche Diagnostics Norway, Etterstad, PO Box 6610, 0607, Oslo, Norway

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Oslo University Hospital, Nydalen, PO Box 4650, 0424, Oslo, Norway

    Guro Haugen Fossum & Jon Mork

  2. Department of Pathology, Oslo University Hospital, Nydalen, PO Box 4650, 0424, Oslo, Norway

    Agnes Kathrine Lie, Peter Jebsen & Lars Erik Sandlie

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  1. Guro Haugen Fossum
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Correspondence to Jon Mork.

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Funding

This study received no external funding.

Conflict of interest

Lars Erik Sandlie presently works for Roche Norway, but had no affiliation with the company, while this study was performed. Guro Fossum Haugen, Agnes Kathrine Lie, Peter Jebsen, and Jon Mork declare that they have no conflict of interest.

Human and animal rights statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Fossum, G.H., Lie, A.K., Jebsen, P. et al. Human papillomavirus in oropharyngeal squamous cell carcinoma in South-Eastern Norway: prevalence, genotype, and survival. Eur Arch Otorhinolaryngol 274, 4003–4010 (2017). https://doi.org/10.1007/s00405-017-4748-8

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  • DOI: https://doi.org/10.1007/s00405-017-4748-8

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