Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus–driven oropharyngeal cancer and are associated with recurrence

Krystle A. Lang Kuhs, Aimée R. Kreimer, Sumita Trivedi, Dana Holzinger, Michael Pawlita, Ruth M. Pfeiffer, Sandra P. Gibson, Nicole C. Schmitt, Allan Hildesheim, Tim Waterboer, Robert L. Ferris

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


BACKGROUND: Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus–driven oropharyngeal cancer (HPV-OPC). METHODS: This study identified 161 incident oropharyngeal cancer (OPC) cases diagnosed at the University of Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing with p16 immunohistochemistry and HPV in situ hybridization (87 were dual-positive [HPV-OPC], and 25 were dual-negative [HPV-negative]); 62 had at least 1 posttreatment serum sample. Eighty-six of the 161 tumors were available for additional HPV16 DNA/RNA testing (45 were dual-positive [HPV16–OPC], and 19 were dual-negative [HPV16–negative). HPV16 E6 antibody testing was conducted with multiplex serology. The following were evaluated: 1) the sensitivity and specificity of HPV16 E6 serology for distinguishing HPV-OPC and HPV16–OPC from HPV-negative OPC, 2) HPV16 E6 antibody decay after treatment with linear models accommodating correlations in variance estimates, and 3) pre- and posttreatment HPV16 E6 levels and the risk of recurrence with Cox proportional hazards models. RESULTS: Seventy-eight of 87 HPV-OPCs were HPV16 E6–seropositive (sensitivity, 89.7%; 95% confidence interval [CI], 81.3%-95.2%), and 24 of 25 HPV-negative OPCs were HPV16 E6–seronegative (specificity, 96.0%; 95% CI, 79.6%-99.9%). Forty-two of 45 HPV16–OPCs were HPV16 E6–seropositive (sensitivity, 93.3%; 95% CI, 81.7%-98.6%), and 18 of 19 HPV16–negative OPCs were HPV16 E6–seronegative (specificity, 94.7%; 95% CI, 74.0%-99.9%). Posttreatment HPV16 E6 antibody levels did not decrease significantly from the baseline (P =.575; median follow-up, 307 days) and were not associated with the risk of recurrence. However, pretreatment HPV16 E6 seropositivity was associated with an 86% reduced risk of local/regional recurrence (hazard ratio, 0.14; 95% CI, 0.03-0.68; P =.015). CONCLUSIONS: HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-OPC. Cancer 2017;123:4382-90.

Original languageEnglish
Pages (from-to)4382-4390
Number of pages9
Issue number22
StatePublished - Nov 15 2017

Bibliographical note

Publisher Copyright:
© 2017 American Cancer Society


  • antibody sensitivity
  • human papillomavirus (HPV)
  • human papillomavirus 16 (HPV16) E6 antibodies
  • recurrence
  • serology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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