Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus

Loizou,Christos; Laurell,Göran; Lindquist,David; Öfverman,Charlotte; Stefansson,Kristina; Nylander,Karin; Olofsson,Katarina

doi:10.3892/ol.2015.3775

Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus

Authors:
- Christos Loizou
- Göran Laurell
- David Lindquist
- Charlotte Öfverman
- Kristina Stefansson
- Karin Nylander
- Katarina Olofsson
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Affiliations: Department of Clinical Sciences, Division of Otorhinolaryngology, Umeå University, S‑901 85 Umeå, Sweden, Department of Radiation Sciences, Division of Oncology, Umeå University, S‑901 85 Umeå, Sweden, Department of Medical Biosciences, Division of Pathology, Umeå University, S‑901 85 Umeå, Sweden
Published online on: October 2, 2015 https://doi.org/10.3892/ol.2015.3775
Pages: 3565-3572

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Abstract

The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2‑fold increase between 1990 and 2013; specifically, a 2.7‑fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV‑positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.

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1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Center for Epidemiology: Cancer incidence in Sweden 2011. National Board of Health and Welfare (SocialStyrelsen) (Stockholm, Sweden). 2011.
3	Lind M, Lewin F, Lundgren J, Nathanson ALF and Strander H: Head, neck and oesophageal cancer: Diagnosis, treatment and follow-up of the Stockholm-Gotland region. Karolinska University Hospital (Stockholm). Oncological Centrum. 2001.(In Swedish) Available from. http://www.cancercentrum.se/Global/RCCSthlmGotland/Regionla%20vårdprogram/HuvudhalsEsofaguscancer2001%5B1%5D.pdfAccessed. July 11–2014
4	Panwar A, Batra R, Lydiatt WM and Ganti AK: Human papilloma virus positive oropharyngeal squamous cell carcinoma: A growing epidemic. Cancer Treat Rev. 40:215–219. 2014. View Article : Google Scholar : PubMed/NCBI
5	Hammarstedt L, Lindquist D, Dahlstrand H, Romanitan M, Dahlgren LO, Joneberg J, Creson N, Lindholm J, Ye W, Dalianis T and Munck-Wikland E: Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer. 119:2620–2623. 2006. View Article : Google Scholar : PubMed/NCBI
6	Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH and Ang KK: Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 30:2102–2111. 2012. View Article : Google Scholar : PubMed/NCBI
7	Blomberg M, Nielsen A, Munk C and Kjaer SK: Trends in head and neck cancer incidence in Denmark, 1978-2007: Focus on human papillomavirus associated sites. Int J Cancer. 129:733–741. 2011. View Article : Google Scholar : PubMed/NCBI
8	Olaleye O, Moorthy R, Lyne O, Black M, Mitchell D and Wiseberg J: A 20-year retrospective study of tonsil cancer incidence and survival trends in South East England: 1987-2006. Clin Otolaryngol. 36:325–335. 2011. View Article : Google Scholar : PubMed/NCBI
9	Klussmann JP, Weissenborn SJ, Wieland U, Dries V, Eckel HE, Pfister HJ and Fuchs PG: Human papillomavirus-positive tonsillar carcinomas: A different tumor entity? Med Microbiol Immunol. 192:129–132. 2003.(In Swedish). View Article : Google Scholar : PubMed/NCBI
10	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
11	Haughey BH, Hinni ML, Salassa JR, et al: Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: A United States multicenter study. Head Neck. 33:1683–1694. 2011. View Article : Google Scholar : PubMed/NCBI
12	Richmon JD, Quon H and Gourin CG: The effect of transoral robotic surgery on short-term outcomes and cost of care after oropharyngeal cancer surgery. Laryngoscope. 124:165–171. 2014. View Article : Google Scholar : PubMed/NCBI
13	Nichols AC, Faquin WC, Westra WH, Mroz EA, Begum S, Clark JR and Rocco JW: 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
14	O'Rorke MA, Ellison MV, Murray LJ, Moran M, James J and Anderson LA: Human papillomavirus related head and neck cancer survival: A systematic review and meta-analysis. Oral Oncol. 48:1191–1201. 2012. View Article : Google Scholar : PubMed/NCBI
15	Mellin H, Friesland S, Lewensohn R, Dalianis T and Munck-Wikland E: Human papillomavirus (HPV) DNA in tonsillar cancer: Clinical correlates, risk of relapse and survival. Int J Cancer. 89:300–304. 2000. View Article : Google Scholar : PubMed/NCBI
16	Schiffman M and Castle PE: Human papillomavirus: Epidemiology and public health. Arch Pathol Lab Med. 127:930–934. 2003.PubMed/NCBI
17	D'souza G and Dempsey A: The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med. 55(Suppl 1): S5–S11. 2011. View Article : Google Scholar
18	Steinau M, Saraiya M, Goodman MT, Peters ES, Watson M, Cleveland JL, Lynch CF, Wilkinson EJ, Hernandez BY and Copeland G: Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States. Emerg Infect Dis. 20:822–828. 2014. View Article : Google Scholar : PubMed/NCBI
19	Osazuwa-Peters N: Human papillomavirus (HPV), HPV-associated oropharyngeal cancer and HPV vaccine in the United States-do we need a broader vaccine policy? Vaccine. 31:5500–5505. 2013. View Article : Google Scholar : PubMed/NCBI
20	Williams JR: The Declaration of Helsinki and public health. Bull World Health Organ. 86:650–652. 2008. View Article : Google Scholar : PubMed/NCBI
21	de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ and Snijders PJ: The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol. 76:1057–1062. 1995. View Article : Google Scholar : PubMed/NCBI
22	Smits HL, Tieben LM, Tjong-A-Hung SP, Jebbink MF, Minnaar RP, Jansen CL and ter Schegget J: Detection and typing of human papillomaviruses present in fixed and stained archival cervical smears by a consensus polymerase chain reaction and direct sequence analysis allow the identification of a broad spectrum of human papillomavirus types. J Gen Virol. 73:3263–3268. 1992. View Article : Google Scholar : PubMed/NCBI
23	Detre S, Saclani Jotti G and Dowsett M: A ‘quickscore’ method for immunohistochemical semiquantitation: Validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 48:876–878. 1995. View Article : Google Scholar : PubMed/NCBI
24	Sweden Official Statistics: Urban areas 2010. Statistical Central Office (Stockholm, Sweden). 2012.(In Swedish).
25	Sweden Official Statistics: Smaller localities 2010. Statistical Central Office (Stockholm, Sweden). 2012.(In Swedish).
26	Nordlund LA: Trends in smoking habits and lung cancer in Sweden. Eur J Cancer Prev. 7:109–116. 1998.PubMed/NCBI
27	Golas SM: Trends in palatine tonsillar cancer incidence and mortality rates in the United States. Community Dent Oral Epidemiol. 35:98–108. 2007. View Article : Google Scholar : PubMed/NCBI
28	Hammarstedt L, Dahlstrand H, Lindquist D, et al: The incidence of tonsillar cancer in Sweden is increasing. Acta Otolaryngol. 127:988–992. 2007. View Article : Google Scholar : PubMed/NCBI
29	Näsman A, Attner P, Hammarstedt L, et al: Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral-induced carcinoma? Int J Cancer. 125:362–366. 2009. View Article : Google Scholar : PubMed/NCBI
30	Dahlstrand HM and Dalianis T: Presence and influence of human papillomaviruses (HPV) in Tonsillar cancer. Adv Cancer Res. 93:59–89. 2005. View Article : Google Scholar : PubMed/NCBI
31	Syrjänen S: HPV infections and tonsillar carcinoma. J Clin Pathol. 57:449–455. 2004. View Article : Google Scholar : PubMed/NCBI
32	Oguejiofor KK, Hall JS, Mani N, et al: The Prognostic Significance of the Biomarker p16 in Oropharyngeal Squamous Cell Carcinoma. Clin Oncol (R Coll Radiol). 25:630–638. 2013. View Article : Google Scholar : PubMed/NCBI
33	Mellin Dahlstrand H, Lindquist D, Björnestål L, et al: P16(INK4a) correlates to human papillomavirus presence, response to radiotherapy and clinical outcome in tonsillar carcinoma. Anticancer Res. 25:4375–4383. 2005.PubMed/NCBI
34	Weinberger PM, Yu Z, Haffty BG, et al: Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 24:736–747. 2006. View Article : Google Scholar : PubMed/NCBI
35	Lindquist D, Romanitan M, Hammarstedt L, Näsman A, Dahlstrand H, Lindholm J, Onelöv L, Ramqvist T, Ye W, Munck-Wikland E and Dalianis T: Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol. 1:350–355. 2007. View Article : Google Scholar : PubMed/NCBI
36	Fischer CA, Kampmann M, Zlobec I, Green E, Tornillo L, Lugli A, Wolfensberger M and Terracciano LM: p16 expression in oropharyngeal cancer: Its impact on staging and prognosis compared with the conventional clinical staging parameters. Ann Oncol. 21:1961–1966. 2010. View Article : Google Scholar : PubMed/NCBI
37	Goldenberg D, Begum S, Westra WH, Khan Z, Sciubba J, Pai SI, Califano JA, Tufano RP and Koch WM: Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon. Head Neck. 30:898–903. 2008. View Article : Google Scholar : PubMed/NCBI
38	Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J and Overgaard J: Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 27:1992–1998. 2009. View Article : Google Scholar : PubMed/NCBI
39	Marklund L and Hammarstedt L: Impact of HPV in Oropharyngeal Cancer. J Oncol. 2011:5090362011. View Article : Google Scholar : PubMed/NCBI
40	Hemminki K, Dong C and Frisch M: Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. Eur J Cancer Prev. 9:433–437. 2000. View Article : Google Scholar : PubMed/NCBI
41	Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, Graubard BI and Chaturvedi AK: Prevalence of oral HPV infection in the United States, 2009-2010. Jama. 307:693–703. 2012. View Article : Google Scholar : PubMed/NCBI