PMID- 28939080 OWN - NLM STAT- MEDLINE DCOM- 20180614 LR - 20180708 IS - 1879-0593 (Electronic) IS - 1368-8375 (Linking) VI - 73 DP - 2017 Oct TI - Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils. PG - 77-82 LID - S1368-8375(17)30244-0 [pii] LID - 10.1016/j.oraloncology.2017.08.010 [doi] AB - OBJECTIVES: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils. METHODS: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n=237) and in 2015 (Group B, n=240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types. Tonsillar DNA and peripheral blood leukocyte DNA from the infected individuals were analyzed using Nimblegen SeqCap EZ Comprehensive Cancer Design panel. The panel targets 578 different genes that are relevant in carcinogenesis. HPV negative tonsillar specimens from age- and gender matched individuals were used as controls. All specimens harboring high-risk HPV were analyzed using fluorescence in situ hybridization (FISH). RESULTS: Five of 477 (1.0%) patients tested positive for the following HPV types: HPV16 (two cases), HPV52 (one case), HPV66 (one case), HPV52 and HPV68 (coinfection, one case). FISH analyses showed that the appearance of HPV in specimens infected with HPV 16 was episomal. Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC). CONCLUSIONS: The prevalence of high-risk HPV in nonmalignant tonsils is low. High-risk HPV positive tonsils harbored mutations in genes that are commonly altered in HPV-associated head and neck SCC. The role of these mutations in tonsillar carcinogenesis is an interesting target for future research. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Ilmarinen, Taru AU - Ilmarinen T AD - Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00130 Helsinki, Finland. Electronic address: taru.t.ilmarinen@hus.fi. FAU - Munne, Pauliina AU - Munne P AD - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, P.O. Box 20, 00014 Helsinki, Finland. FAU - Hagstrom, Jaana AU - Hagstrom J AD - Department of Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 21, 00014 Helsinki, Finland. FAU - Haglund, Caj AU - Haglund C AD - Department of Surgery and Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 21, 00014 Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 21, 00014 Helsinki, Finland. FAU - Auvinen, Eeva AU - Auvinen E AD - Department of Virology, University of Helsinki and Helsinki University Hospital Laboratory, P.O. Box 21, 00014 Helsinki, Finland. FAU - Virtanen, Elina I AU - Virtanen EI AD - Department of Virology, University of Helsinki and Helsinki University Hospital Laboratory, P.O. Box 21, 00014 Helsinki, Finland. FAU - Haesevoets, Annick AU - Haesevoets A AD - Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. FAU - Speel, Ernst J M AU - Speel EJM AD - Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. FAU - Aaltonen, Leena-Maija AU - Aaltonen LM AD - Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00130 Helsinki, Finland. LA - eng PT - Journal Article DEP - 20170818 PL - England TA - Oral Oncol JT - Oral oncology JID - 9709118 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Child MH - Child, Preschool MH - Female MH - Human papillomavirus 16/isolation & purification MH - Humans MH - Infant MH - Male MH - Middle Aged MH - *Mutation MH - Palatine Tonsil/*metabolism MH - Prevalence MH - Risk Factors MH - Tonsillar Neoplasms/genetics/virology MH - Young Adult OTO - NOTNLM OT - Cancer gene OT - Human papillomavirus OT - Mutation OT - Squamous cell carcinoma OT - Tonsil EDAT- 2017/09/25 06:00 MHDA- 2018/06/15 06:00 CRDT- 2017/09/24 06:00 PHST- 2017/04/15 00:00 [received] PHST- 2017/08/11 00:00 [revised] PHST- 2017/08/14 00:00 [accepted] PHST- 2017/09/24 06:00 [entrez] PHST- 2017/09/25 06:00 [pubmed] PHST- 2018/06/15 06:00 [medline] AID - S1368-8375(17)30244-0 [pii] AID - 10.1016/j.oraloncology.2017.08.010 [doi] PST - ppublish SO - Oral Oncol. 2017 Oct;73:77-82. doi: 10.1016/j.oraloncology.2017.08.010. Epub 2017 Aug 18.