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@ARTICLE{Holzinger:120649,
      author       = {D. Holzinger$^*$ and G. Wichmann and L. Baboci$^*$ and A.
                      Michel$^*$ and D. Höfler$^*$ and M. Wiesenfarth$^*$ and L.
                      Schroeder$^*$ and P. Boscolo-Rizzo and C. Herold-Mende$^*$
                      and G. Dyckhoff and A. Boehm and A. Del Mistro and F. X.
                      Bosch and A. Dietz and M. Pawlita$^*$ and T. Waterboer$^*$},
      title        = {{S}ensitivity and specificity of antibodies against {HPV}16
                      {E}6 and other early proteins for the detection of
                      {HPV}16-driven oropharyngeal squamous cell carcinoma.},
      journal      = {International journal of cancer},
      volume       = {140},
      number       = {12},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-01076},
      pages        = {2748 - 2757},
      year         = {2017},
      abstract     = {To determine the sensitivity and specificity of HPV16
                      serology as diagnostic marker for HPV16-driven oropharyngeal
                      squamous cell carcinoma (OPSCC), 214 HNSCC patients from
                      Germany and Italy with fresh-frozen tumor tissues and sera
                      collected before treatment were included in this study.
                      Hundred and twenty cancer cases were from the oropharynx and
                      94 were from head and neck cancer regions outside the
                      oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx).
                      Serum antibodies to early (E1, E2, E6 and E7) and late (L1)
                      HPV16 proteins were analyzed by multiplex serology and were
                      compared to tumor HPV RNA status as the gold standard. A
                      tumor was defined as HPV-driven in the presence of HPV16 DNA
                      and HPV16 transformation-specific RNA transcript patterns
                      (E6*I, E1(∧) E4 and E1C). Of 120 OPSCC, 66 $(55\%)$ were
                      HPV16-driven. HPV16 E6 seropositivity was the best predictor
                      of HPV16-driven OPSCC (diagnostic accuracy $97\%$ $[95\%CI$
                      $92-99\%],$ Cohen's kappa 0.93 $[95\%CI$ 0.8-1.0]). Of the
                      66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared
                      to only one $(1.8\%)$ among the 54 non-HPV-driven OPSCC,
                      resulting in a sensitivity of $96\%$ $(95\%CI$ 88-98) and a
                      specificity of $98\%$ $(95\%CI$ 90-100). Of 94 HNSCC outside
                      the oropharynx, six $(6\%)$ were HPV16-driven. In these
                      patients, HPV16 E6 seropositivity had lower sensitivity
                      $(50\%,$ $95\%CI$ 19-81), but was highly specific $(100\%,$
                      $95\%CI$ 96-100). In conclusion, HPV16 E6 seropositivity
                      appears to be a highly reliable diagnostic marker for
                      HPV16-driven OPSCC with very high sensitivity and
                      specificity, but might be less sensitive for HPV16-driven
                      HNSCC outside the oropharynx.},
      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:28316084},
      doi          = {10.1002/ijc.30697},
      url          = {https://inrepo02.dkfz.de/record/120649},
}