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Oral Oncol. 2017 Oct;73:77-82. doi: 10.1016/j.oraloncology.2017.08.010. Epub 2017 Aug 18.

Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils.

Author information

1
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.
2
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, P.O. Box 20, 00014 Helsinki, Finland.
3
Department of Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 21, 00014 Helsinki, Finland.
4
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.
5
Department of Virology, University of Helsinki and Helsinki University Hospital Laboratory, P.O. Box 21, 00014 Helsinki, Finland.
6
Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
7
Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 263, 00130 Helsinki, Finland.

Abstract

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.

KEYWORDS:

Cancer gene; Human papillomavirus; Mutation; Squamous cell carcinoma; Tonsil

[Indexed for MEDLINE]

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