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

• Published in: Cancer 2017-11, Vol.123 (22), p.4382-4390
• Main Authors: Lang Kuhs, Krystle A., Kreimer, Aimée R., Trivedi, Sumita, Holzinger, Dana, Pawlita, Michael, Pfeiffer, Ruth M., Gibson, Sandra P., Schmitt, Nicole C., Hildesheim, Allan, Waterboer, Tim, Ferris, Robert L.
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies, Viral - blood; Antibody response; antibody sensitivity; Cancer; Cell Transformation, Viral - immunology; Confidence intervals; Deoxyribonucleic acid; Diagnosis; DNA; Female; Hazards; Health risk assessment; Human papillomavirus; human papillomavirus (HPV); human papillomavirus 16 (HPV16) E6 antibodies; Human papillomavirus 16 - immunology; Humans; Immunoglobulins; Immunohistochemistry; Male; Middle Aged; Multiplexing; Oncogene Proteins, Viral - immunology; Oncology; Oropharyngeal cancer; Oropharyngeal Neoplasms - blood; Oropharyngeal Neoplasms - diagnosis; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; Papillomavirus Infections - blood; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; Papillomavirus Infections - pathology; Predictive Value of Tests; Prognosis; Recurrence; Repressor Proteins - immunology; Ribonucleic acid; Risk; RNA; Sensitivity; Sensitivity analysis; Sensitivity and Specificity; Serology; Statistical models; Throat cancer; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30966

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. © 2017 American Cancer Society. Human papillomavirus 16 E6 antibodies may be a marker of the diagnosis and recurrence of human papillomavirus–driven oropharyngeal cancer. The vast majority of patients with human papillomavirus–driven oropharyngeal cancer mount a human papillomavirus 16 E6 antibody response at the time of diagnosis, and those who do not mount an antibody response are at the highest risk of recurre