Yuehan Zhang1, Tim Waterboer2, Robert I Haddad3, Brett A Miles4, Alicia Wentz1, Neil D Gross5, Carole Fakhry6, Harry Quon7, Jochen H Lorch3, Christine G Gourin6, Daniel Clayburgh8, Krzysztof J Misiukiewicz9, Jeremy D Richmon6, Peter E Andersen8, Marshall R Posner9, Gypsyamber D'Souza10. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. 2. German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. 3. Department of Adult Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. 4. Department of Otolaryngology, Icahn School of Medicine at Mount Sinai Medical Center, 1 Gustave L. Levy Pl, New York, NY 10029, USA. 5. Division of Surgery, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. 6. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA. 7. Department of Radiation Oncology, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA. 8. Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OH 97239, USA. 9. Tisch Cancer Institute, Head and Neck Oncology Center, Icahn School of Medicine at Mount Sinai Medical Center, 1 Gustave L. Levy Pl, New York, NY 10029, USA. 10. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: gdsouza2@jhu.edu.
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 3years 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.
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-OPCpatients for more individualized surveillance intensity and which remain at higher recurrence risk. MATERIALS AND METHODS: 115 HPV-OPCpatients (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 3years 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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