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The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review

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Abstract

A subset of head and neck squamous cell carcinoma, which mainly arise from the crypt epithelium of the palatine and lingual tonsils, may be caused by high-risk human papillomavirus (HPV) infections. This topographical restriction together with other overlapping clinical features have led investigators to suspect that HPV plays a role in squamous cell carcinoma of unknown primary (SCCUP) site metastatic to neck lymph nodes. We performed a systematic review of articles listed in PubMed to identify studies testing HPV and/or p16INK4a status (p16) in tissue samples from initial and definitive SCCUP. The prevalence of HPV-related (HPV DNA-positive and/or p16 positive) SCCUP was calculated for all the SCCUP, initial SCCUP, suspected definitive SCCUP, and true definitive SCCUP whenever a minimum of 10 cases of each category was identified. In addition, data concerning patients’ diagnostic work-up, the HPV detection methods, and the correlations between HPV-status, the localization of the occult primary tumor, and the clinical outcome were also extracted. Eighteen retrospective cohort studies, assessing a total of 659 patients, met the inclusion criteria. The overall median prevalences of HPV-DNApos, of p16pos, and of positivity for both HPV markers were, respectively, 37.0, 48.5, and 36.0 %. Patients with diagnosis of initial SCCUP had overall median prevalences of HPV-DNApos, of p16pos, and of positivity for both HPV markers, respectively, of 81.8, 86.2, and 80.8 %. The data uncovered by this systematic review confirm that SCCUP is frequently causally associated to HPV-driven oropharyngeal squamous cell carcinomas. This finding supports the view that HPV-status could be routinely assessed in SCCUP patients as it may lead to identifying the primary tumor and the decision to de-escalate treatment.

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Acknowledgments

The authors would like to thank Prof. Annette Kopp-Schneider for her assistance in statistical analysis. Support by the DKFZ light microscopy facility is gratefully acknowledged. PBR has been awarded a scholarship from the DAAD (Deutsche Akademische Austauschdienst). We would also like to express thanks to the authors of the original studies who provided additional information for this review.

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Authors and Affiliations

  1. Department of Neurosciences, Regional Center for Head and Neck Cancer, University of Padua, P.le Ospedale 1, 31100, Treviso, Italy

    Paolo Boscolo-Rizzo

  2. Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection and Cancer, German Cancer Research Center (DKFZ), F020, Heidelberg, Germany

    Lea Schroeder & Michael Pawlita

  3. Department of Pathology, Treviso Regional Hospital, Treviso, Italy

    Salvatore Romeo

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  1. Paolo Boscolo-Rizzo
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Correspondence to Paolo Boscolo-Rizzo.

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Conflict of interest

MP received research funding from cooperation contracts with DKFZ, with Roche and Qiagen. He is also the inventor and receives royalties on patents held by DKFZ in the field of molecular diagnostics for infectious disease.

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Boscolo-Rizzo, P., Schroeder, L., Romeo, S. et al. The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review. Clin Exp Metastasis 32, 835–845 (2015). https://doi.org/10.1007/s10585-015-9744-z

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  • DOI: https://doi.org/10.1007/s10585-015-9744-z

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