TY - JOUR
T1 - Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus–driven oropharyngeal cancer and are associated with recurrence
AU - Lang Kuhs, Krystle A.
AU - Kreimer, Aimée R.
AU - Trivedi, Sumita
AU - Holzinger, Dana
AU - Pawlita, Michael
AU - Pfeiffer, Ruth M.
AU - Gibson, Sandra P.
AU - Schmitt, Nicole C.
AU - Hildesheim, Allan
AU - Waterboer, Tim
AU - Ferris, Robert L.
N1 - Funding Information:
This study was supported by the Intramural Research Program of the US National Institutes of Health (Division of Cancer Epidemiology and Genetics, National Cancer Institute), by the US National Institutes of Health through grants R01 CA206517, P50 CA097190, and T32 CA060397, and by the Tumor Microenvironment/Virus Oncology Center of the University of Pittsburgh Medical Center.
Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/11/15
Y1 - 2017/11/15
N2 - 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.
AB - 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.
KW - antibody sensitivity
KW - human papillomavirus (HPV)
KW - human papillomavirus 16 (HPV16) E6 antibodies
KW - recurrence
KW - serology
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U2 - 10.1002/cncr.30966
DO - 10.1002/cncr.30966
M3 - Article
C2 - 28950407
AN - SCOPUS:85032792767
SN - 0008-543X
VL - 123
SP - 4382
EP - 4390
JO - Cancer
JF - Cancer
IS - 22
ER -