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@ARTICLE{Schroeder:120666,
      author       = {L. Schroeder$^*$ and P. Boscolo-Rizzo and E. Dal Cin and S.
                      Romeo and L. Baboci$^*$ and G. Dyckhoff and J. Hess$^*$ and
                      C. Lucena-Porcel and A. Byl and N. Becker and L. Alemany and
                      X. Castellsagué and M. Quer and X. León and M.
                      Wiesenfarth$^*$ and M. Pawlita$^*$ and D. Holzinger$^*$},
      title        = {{H}uman papillomavirus as prognostic marker with rising
                      prevalence in neck squamous cell carcinoma of unknown
                      primary: {A} retrospective multicentre study.},
      journal      = {European journal of cancer},
      volume       = {74},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2017-01092},
      pages        = {73 - 81},
      year         = {2017},
      abstract     = {Patients with neck squamous cell carcinomas of unknown
                      primary tumour (NSCCUP) present with lymph node metastasis
                      without evidence for a primary tumour. Most patients undergo
                      an aggressive multimodal treatment, which induces severe,
                      potentially unnecessary toxicity. Primary tumours of NSCCUP
                      can be hidden in the oropharynx. Human papillomavirus (HPV)
                      is causally involved in a subgroup of oropharyngeal squamous
                      cell carcinomas (OPSCC) associated with early lymph node
                      metastasis and good prognosis. Detection of markers for HPV
                      transformation in NSCCUP could allow focussing on the
                      oropharynx in primary tumour search and could be of value
                      for choice and extent of treatment. In a retrospective
                      multicentre study (Germany, Italy and Spain), we analysed
                      metastatic lymph nodes from 180 NSCCUP patients for the
                      presence of HPV DNA, HPV E6*I mRNA and cellular p16(INK4a)
                      overexpression, a surrogate marker for HPV-induced
                      transformation. HPV status, defined as positivity for viral
                      mRNA with at least one additional marker, was correlated
                      with clinical parameters and survival outcome. A substantial
                      proportion $(16\%)$ of NSCCUP were HPV-driven, mainly by
                      HPV16 $(89\%).$ HPV prevalence increased with year of
                      diagnosis from $9\%$ during 1998-2004 to $23\%$ during
                      2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly
                      better overall and progression-free survival rates
                      (p ≤ 0.008). Based on this survival benefit, it is
                      contended that HPV RNA status should be included in NSCCUP
                      diagnosis and in therapeutic decision-making.
                      Deintensification of radiation in patients with HPV-driven
                      NSCCUP, while concurrently concentrating on the oropharynx
                      appears to be a promising therapeutic strategy, the efficacy
                      of which should be assessed in prospective trials. To our
                      knowledge, this is the largest study on HPV in NSCCUP.},
      cin          = {F020 / G405 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)F020-20160331 / I:(DE-He78)G405-20160331 /
                      I:(DE-He78)C060-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28335889},
      doi          = {10.1016/j.ejca.2016.12.020},
      url          = {https://inrepo02.dkfz.de/record/120666},
}