TY - JOUR
T1 - Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma
AU - Taberna, M.
AU - Resteghini, C.
AU - Swanson, B.
AU - Pickard, R. K.L.
AU - Jiang, B.
AU - Xiao, W.
AU - Mena, M.
AU - Kreinbrink, P.
AU - Chio, E.
AU - Gillison, M. L.
N1 - Funding Information:
MT gratefully acknowledge the Rio Hortega-SEOM (ISCIII: Instituto de Salud Carlos III-Spanish Society of Medical Oncology) grant and the University of Barcelona for their support on her fellowship.
Publisher Copyright:
© 2016
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
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.
KW - HPV DNA PCR
KW - HPV E6/E7 mRNA qRT-PCR
KW - HPV11
KW - Head and neck cancer
KW - Head and neck squamous cell carcinoma
KW - Human papillomavirus
KW - Larynx cancer
KW - p16 immunohistochemistry
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U2 - 10.1016/j.oraloncology.2016.08.009
DO - 10.1016/j.oraloncology.2016.08.009
M3 - Article
C2 - 27688105
AN - SCOPUS:84984638443
SN - 1368-8375
VL - 61
SP - 55
EP - 61
JO - Oral Oncology
JF - Oral Oncology
ER -