Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma

Dana Holzinger, Gunnar Wichmann, Lorena Baboci, Angelika Michel, Daniela Höfler, Manuel Wiesenfarth, Lea Schroeder, Paolo Boscolo-Rizzo, Christel Herold-Mende, Gerhard Dyckhoff, Andreas Boehm, Annarosa Del Mistro, Franz X Bosch, Andreas Dietz, Michael Pawlita, Tim Waterboer

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2748-2757
Number of pages10
JournalInternational Journal of Cancer
Issue number12
Publication statusPublished - Jun 15 2017


  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral
  • Carcinoma, Squamous Cell
  • Female
  • Host-Pathogen Interactions
  • Human papillomavirus 16
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral
  • Oropharyngeal Neoplasms
  • Papillomavirus Infections
  • Repressor Proteins
  • Sensitivity and Specificity
  • Journal Article
  • Multicenter Study
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma'. Together they form a unique fingerprint.

Cite this