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@ARTICLE{Schroeder:132513,
      author       = {L. Schroeder$^*$ and G. Wichmann and M. Willner and A.
                      Michel$^*$ and M. Wiesenfarth$^*$ and C. Flechtenmacher and
                      T. Gradistanac and M. Pawlita$^*$ and A. Dietz and T.
                      Waterboer$^*$ and D. Holzinger$^*$},
      title        = {{A}ntibodies against human papillomaviruses as diagnostic
                      and prognostic biomarker in patients with neck squamous cell
                      carcinoma from unknown primary tumor.},
      journal      = {International journal of cancer},
      volume       = {142},
      number       = {7},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2018-00200},
      pages        = {1361 - 1368},
      year         = {2018},
      abstract     = {Treatment of patients with neck lymph node metastasis of
                      squamous cell carcinoma (SCC) from unknown primary tumor
                      (NSCCUP) is challenging due to the risk of missing occult
                      tumors or inducing toxicity to unaffected sites. Human
                      papillomavirus (HPV) is a promising biomarker given its
                      causal link to oropharyngeal SCC and superior survival of
                      patients with HPV-driven oropharyngeal SCC and NSCCUP.
                      Identification of HPV-driven NSCCUP could focus diagnostic
                      work-up and treatment on the oropharynx. For the first time,
                      we assessed HPV antibodies and their prognostic value in
                      NSCCUP patients. Antibodies against E6 and E7
                      (HPV16/18/31/33/35), E1 and E2 (HPV16/18) were assessed in
                      46 NSCCUP patients in sera collected at diagnosis, and in
                      follow-up sera from five patients. In 28 patients, HPV tumor
                      status was determined using molecular markers (HPV DNA, mRNA
                      and cellular p16INK4a). Thirteen $(28\%)$ NSCCUP patients
                      were HPV-seropositive for HPV16, 18, 31, or 33. Of eleven
                      patients with HPV-driven NSCCUP, ten were HPV-seropositive,
                      while all 17 patients with non-HPV-driven NSCCUP were
                      HPV-seronegative, resulting in $91\%$ sensitivity $(95\%$
                      CI: $59-100\%)$ and $100\%$ specificity $(95\%$ CI:
                      $80-100\%).$ HPV antibody levels decreased after curative
                      treatment. Recurrence was associated with increasing levels
                      in an individual case. HPV-seropositive patients had a
                      better overall and progression-free survival with hazard
                      ratios of 0.09 $(95\%$ CI: 0.01-0.42) and 0.03 $(95\%$ CI:
                      0.002-0.18), respectively. For the first time,
                      seropositivity to HPV proteins is described in NSCCUP
                      patients, and high sensitivity and specificity for
                      HPV-driven NSCCUP are demonstrated. HPV seropositivity
                      appears to be a reliable diagnostic and prognostic biomarker
                      for patients with HPV-driven NSCCUP.},
      cin          = {F020 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)F020-20160331 / 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:29159804},
      doi          = {10.1002/ijc.31167},
      url          = {https://inrepo02.dkfz.de/record/132513},
}