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Ann Oncol. 2019 Aug 1;30(8):1335-1343. doi: 10.1093/annonc/mdz138.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

Author information

1
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
2
Genetic Epidemiology Group (GEP), International Agency for Research on Cancer (IARC), Lyon, France.
3
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
4
Infections and Cancer Epidemiology, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo.
6
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx.
7
Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA.
8
HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
9
Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
10
Cancer Registry of Norway, Institute of Population-Based Cancer Research, Majorstuen, Oslo.
11
Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
12
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
13
Genetic Epidemiology Group, Folkhälsan Research Center, and Faculty of Medicine, Helsinki University, Helsinki, Finland.
14
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
15
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne.
16
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Parkville.
17
School of Public Health and Preventive Medicine, Monash University Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne.
18
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.
19
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, USA.
20
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
21
Navarra Public Health Institute, Pamplona.
22
Navarra Institute for Health Research (IdiSNA), Pamplona.
23
CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
24
Danish Cancer Society Research Center, Copenhagen, Denmark.
25
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
26
Hellenic Health Foundation, Athens, Greece.
27
Institute for Risk Assessment Sciences, Utrecht University; Julius Centre for Public Health Sciences and Primary Care, Utrecht University Medical Centre, Utrecht, the Netherlands.

Abstract

BACKGROUND:

Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown.

PATIENTS AND METHODS:

We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay).

RESULTS:

HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis.

CONCLUSIONS:

The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

KEYWORDS:

HPVC3; OPCSCC; oropharyngeal squamous cell carcinoma

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