Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma

M. Taberna, C. Resteghini, Benjamin J Swanson, R. K L Pickard, B. Jiang, W. Xiao, M. Mena, P. Kreinbrink, E. Chio, M. L. Gillison

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalOral Oncology
Volume61
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Larynx
Squamous Cell Carcinoma
Messenger RNA
Polymerase Chain Reaction
DNA
Neoplasms
Nucleotides
Immunohistochemistry

Keywords

  • Head and neck cancer
  • Head and neck squamous cell carcinoma
  • HPV DNA PCR
  • HPV E6/E7 mRNA qRT-PCR
  • HPV11
  • Human papillomavirus
  • Larynx cancer
  • p16 immunohistochemistry

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

Taberna, M., Resteghini, C., Swanson, B. J., Pickard, R. K. L., Jiang, B., Xiao, W., ... Gillison, M. L. (2016). Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma. Oral Oncology, 61, 55-61. https://doi.org/10.1016/j.oraloncology.2016.08.009

Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma. / Taberna, M.; Resteghini, C.; Swanson, Benjamin J; Pickard, R. K L; Jiang, B.; Xiao, W.; Mena, M.; Kreinbrink, P.; Chio, E.; Gillison, M. L.

In: Oral Oncology, Vol. 61, 01.10.2016, p. 55-61.

Research output: Contribution to journalArticle

Taberna, M, Resteghini, C, Swanson, BJ, Pickard, RKL, Jiang, B, Xiao, W, Mena, M, Kreinbrink, P, Chio, E & Gillison, ML 2016, 'Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma', Oral Oncology, vol. 61, pp. 55-61. https://doi.org/10.1016/j.oraloncology.2016.08.009
Taberna, M. ; Resteghini, C. ; Swanson, Benjamin J ; Pickard, R. K L ; Jiang, B. ; Xiao, W. ; Mena, M. ; Kreinbrink, P. ; Chio, E. ; Gillison, M. L. / Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma. In: Oral Oncology. 2016 ; Vol. 61. pp. 55-61.
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title = "Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma",
abstract = "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.",
keywords = "Head and neck cancer, Head and neck squamous cell carcinoma, HPV DNA PCR, HPV E6/E7 mRNA qRT-PCR, HPV11, Human papillomavirus, Larynx cancer, p16 immunohistochemistry",
author = "M. Taberna and C. Resteghini and Swanson, {Benjamin J} and Pickard, {R. K L} and B. Jiang and W. Xiao and M. Mena and P. Kreinbrink and E. Chio and Gillison, {M. L.}",
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T1 - Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma

AU - Taberna, M.

AU - Resteghini, C.

AU - Swanson, Benjamin J

AU - Pickard, R. K L

AU - Jiang, B.

AU - Xiao, W.

AU - Mena, M.

AU - Kreinbrink, P.

AU - Chio, E.

AU - Gillison, M. L.

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 - Head and neck cancer

KW - Head and neck squamous cell carcinoma

KW - HPV DNA PCR

KW - HPV E6/E7 mRNA qRT-PCR

KW - HPV11

KW - Human papillomavirus

KW - Larynx cancer

KW - p16 immunohistochemistry

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