Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

Yuehan Zhang, Tim Waterboer, Robert I. Haddad, Brett A. Miles, Alicia Wentz, Neil D. Gross, Carole Fakhry, Harry Quon, Jochen H. Lorch, Christine G. Gourin, Daniel Clayburgh, Krzysztof J. Misiukiewicz, Jeremy D. Richmon, Peter Andersen, Marshall R. Posner, Gypsyamber D'Souza

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95%CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalOral Oncology
Volume67
DOIs
StatePublished - Apr 1 2017

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Oropharyngeal Neoplasms
Human papillomavirus 16
Antibodies
Recurrence
Therapeutics
Seroepidemiologic Studies
Standard of Care
In Situ Hybridization
Biomarkers
Immunohistochemistry
Prospective Studies

Keywords

  • Antibodies
  • E6
  • HPV
  • OPSCC
  • Seroprevalence

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment. / Zhang, Yuehan; Waterboer, Tim; Haddad, Robert I.; Miles, Brett A.; Wentz, Alicia; Gross, Neil D.; Fakhry, Carole; Quon, Harry; Lorch, Jochen H.; Gourin, Christine G.; Clayburgh, Daniel; Misiukiewicz, Krzysztof J.; Richmon, Jeremy D.; Andersen, Peter; Posner, Marshall R.; D'Souza, Gypsyamber.

In: Oral Oncology, Vol. 67, 01.04.2017, p. 77-82.

Research output: Contribution to journalArticle

Zhang, Y, Waterboer, T, Haddad, RI, Miles, BA, Wentz, A, Gross, ND, Fakhry, C, Quon, H, Lorch, JH, Gourin, CG, Clayburgh, D, Misiukiewicz, KJ, Richmon, JD, Andersen, P, Posner, MR & D'Souza, G 2017, 'Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment', Oral Oncology, vol. 67, pp. 77-82. https://doi.org/10.1016/j.oraloncology.2017.02.004
Zhang, Yuehan ; Waterboer, Tim ; Haddad, Robert I. ; Miles, Brett A. ; Wentz, Alicia ; Gross, Neil D. ; Fakhry, Carole ; Quon, Harry ; Lorch, Jochen H. ; Gourin, Christine G. ; Clayburgh, Daniel ; Misiukiewicz, Krzysztof J. ; Richmon, Jeremy D. ; Andersen, Peter ; Posner, Marshall R. ; D'Souza, Gypsyamber. / Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment. In: Oral Oncology. 2017 ; Vol. 67. pp. 77-82.
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abstract = "Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85{\%}). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2{\%} and 0{\%} in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95{\%}CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.",
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author = "Yuehan Zhang and Tim Waterboer and Haddad, {Robert I.} and Miles, {Brett A.} and Alicia Wentz and Gross, {Neil D.} and Carole Fakhry and Harry Quon and Lorch, {Jochen H.} and Gourin, {Christine G.} and Daniel Clayburgh and Misiukiewicz, {Krzysztof J.} and Richmon, {Jeremy D.} and Peter Andersen and Posner, {Marshall R.} and Gypsyamber D'Souza",
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T1 - Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

AU - Zhang, Yuehan

AU - Waterboer, Tim

AU - Haddad, Robert I.

AU - Miles, Brett A.

AU - Wentz, Alicia

AU - Gross, Neil D.

AU - Fakhry, Carole

AU - Quon, Harry

AU - Lorch, Jochen H.

AU - Gourin, Christine G.

AU - Clayburgh, Daniel

AU - Misiukiewicz, Krzysztof J.

AU - Richmon, Jeremy D.

AU - Andersen, Peter

AU - Posner, Marshall R.

AU - D'Souza, Gypsyamber

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Y1 - 2017/4/1

N2 - Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95%CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

AB - Objectives Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. Materials and Methods 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. Results At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3 years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p = 0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR] = 1.81, 95%CI = 0.47–6.92). Conclusion This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

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KW - OPSCC

KW - Seroprevalence

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