PMID- 27688105 OWN - NLM STAT- MEDLINE DCOM- 20180206 LR - 20220409 IS - 1879-0593 (Electronic) IS - 1368-8375 (Linking) VI - 61 DP - 2016 Oct TI - Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma. PG - 55-61 LID - S1368-8375(16)30137-3 [pii] LID - 10.1016/j.oraloncology.2016.08.009 [doi] AB - BACKGROUND: Human Papillomavirus (HPV) is a cause of oropharyngeal squamous cell carcinoma (OPSCC), but its pathogenic role in larynx squamous cell carcinoma (LSCC) remains unclear. MATERIAL AND METHODS: A single-institutional, retrospective case-series was performed to estimate the etiological fraction (EF) for HPV in LSCC. Eligible cases included 436 consecutive cases of LSCC diagnosed (2005-2014) at The Ohio State University Medical Center. HPV DNA presence was detected by consensus primer PCR (Inno-LiPa) and HPV type-specific qPCR. HPV E6/E7 mRNA expression was detected by type-specific qRT-PCR. Tumor p16 expression was evaluated by immunohistochemistry (IHC). RESULTS: HPV DNA was detected by Inno-LiPa in 54 of 404 (13.4%, 95% CI 10.2-17.1) evaluable samples but was confirmed by HPV type-specific qPCR in only 14 (3.5%, 95% CI 1.9-5.7). Only 7 of 404 (1.7%, 95% CI 0.7-3.5) LSCC were positive for HPV E6/E7 mRNA expression, including HPV16 (n=4) and 1 each for 11, 26 and 33. In the HPV11-positive tumor, Sanger sequencing discovered 6 nucleotide mutations in the upstream regulation region, E6 and E7. Of 404 LSCC, 18 had strong and diffuse p16 expression. In comparison to a gold standard of HPV E6/E7 mRNA expression, p16 expression had a sensitivity of 71.4% (95% CI 29.0-96.3), specificity of 96.7% (95% CI 94.5-98.3), positive-predictive-value (PPV) of 27.8% (95% CI 9.7-53.5) and negative-predictive-value of 99.5% (95% CI 98.1-99.9). CONCLUSION: The EF for HPV in LSCC is low (1.7%) in a geographic region with high EF for OPSCC. Low-risk HPV may rarely cause LSCC. Finally, p16 expression has poor PPV for HPV in LSCC. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Taberna, M AU - Taberna M AD - Department of Medical Oncology, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; University of Barcelona, Barcelona, Spain. FAU - Resteghini, C AU - Resteghini C AD - Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. FAU - Swanson, B AU - Swanson B AD - Department of Pathology, The Ohio State University Medical Center, Columbus, OH, United States. FAU - Pickard, R K L AU - Pickard RK AD - Department of Medicine, The Ohio State University, Columbus, OH, United States. FAU - Jiang, B AU - Jiang B AD - Department of Medicine, The Ohio State University, Columbus, OH, United States. FAU - Xiao, W AU - Xiao W AD - Department of Medicine, The Ohio State University, Columbus, OH, United States. FAU - Mena, M AU - Mena M AD - Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Kreinbrink, P AU - Kreinbrink P AD - Department of Medicine, The Ohio State University, Columbus, OH, United States. FAU - Chio, E AU - Chio E AD - Department of Otolaryngology, The Ohio State University Medical Center, Columbus, OH, United States. FAU - Gillison, M L AU - Gillison ML AD - Department of Medicine, The Ohio State University, Columbus, OH, United States. Electronic address: maura.gillison@osumc.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160831 PL - England TA - Oral Oncol JT - Oral oncology JID - 9709118 SB - IM MH - Alphapapillomavirus/*isolation & purification MH - Carcinoma, Squamous Cell/*virology MH - Female MH - Humans MH - Laryngeal Neoplasms/*virology MH - Male OTO - NOTNLM OT - HPV DNA PCR OT - HPV E6/E7 mRNA qRT-PCR OT - HPV11 OT - Head and neck cancer OT - Head and neck squamous cell carcinoma OT - Human papillomavirus OT - Larynx cancer OT - p16 immunohistochemistry EDAT- 2016/10/01 06:00 MHDA- 2018/02/07 06:00 CRDT- 2016/10/01 06:00 PHST- 2016/06/27 00:00 [received] PHST- 2016/08/08 00:00 [revised] PHST- 2016/08/22 00:00 [accepted] PHST- 2016/10/01 06:00 [entrez] PHST- 2016/10/01 06:00 [pubmed] PHST- 2018/02/07 06:00 [medline] AID - S1368-8375(16)30137-3 [pii] AID - 10.1016/j.oraloncology.2016.08.009 [doi] PST - ppublish SO - Oral Oncol. 2016 Oct;61:55-61. doi: 10.1016/j.oraloncology.2016.08.009. Epub 2016 Aug 31.