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

Abstract

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.

• Authors: 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
• Journal: Cancer (Cancer) Vol. 123 Issue 22 Pg. 4382-4390 (Nov 15 2017) ISSN: 1097-0142 [Electronic] United States
• PMID: 28950407 (Publication Type: Journal Article)
• Copyright: © 2017 American Cancer Society.

Chemical References

• Antibodies, Viral
• E6 protein, Human papillomavirus type 16
• Oncogene Proteins, Viral
• Repressor Proteins

Topics

• Antibodies, Viral (blood)
• Cell Transformation, Viral (immunology)
• Female
• Human papillomavirus 16 (immunology)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Oncogene Proteins, Viral (immunology)
• Oropharyngeal Neoplasms (blood, diagnosis, pathology, virology)
• Papillomavirus Infections (blood, complications, diagnosis, pathology)
• Predictive Value of Tests
• Prognosis
• Recurrence
• Repressor Proteins (immunology)
• Sensitivity and Specificity