Comparison of HPV Antibodies Measured Prior to Diagnosis of Anal, Cervical, Oropharyngeal, Penile and Vaginal Cancers in the HPV Cancer Cohort Consortium

Antibodies against HPV proteins can provide pre-diagnostic information about cancer development. We described the prevalence of antibodies to proteins of oncogenic HPV types prior to diagnosis of HPV-related cancers. We analysed pre-diagnostic blood from 1700 participants with incident HPV-related cancers (anal = 387, cervical = 274, oropharyngeal = 788, penile = 168, vaginal = 83) and 6221 controls from nine prospective cohorts in Europe, North America and Australia in the HPV Cancer Cohort Consortium. We measured antibodies against E6, E7 and L1 proteins for 6 HPV types, and additionally against E1, E2, E4, E6, E7 and L1 proteins of HPV16 and 18. We described seroprevalence by lead time from blood draw to cancer diagnosis (range: 0-43 years). We found that among oropharyngeal cancers, seroprevalence increased approaching diagnosis for HPV16 E1, E2, E4, E6, E7, L1 and HPV18 E1, E2, L1 (HPV16-E6: from 10.4% at > 20 years to 35.8% at 0-5 years, vs. 0.3% in controls). Anal cancer showed similar patterns for HPV16 E1, E2, E4, E6 and L1 and HPV18 E2 (HPV16-E6: from 3.8% at > 20 years to 29.8% at 0-5 years). No trends were observed for cervical, penile, or vaginal cancers. In a multivariable model fit among cases, HPV16-E6 seropositivity was higher at shorter lead times and more recent calendar periods, lower among US non-Hispanic Blacks, and varied by cancer type (highest in oropharyngeal followed by anal, vaginal, penile and cervical) (all p < 0.03). In conclusion, pre-diagnostic HPV antibody responses vary by cancer type, with seroprevalence of 6-9 HPV proteins increasing approaching diagnosis for oropharyngeal and anal cancers, but not cervical, penile or vaginal cancers.

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Journal
International Journal of Cancer
Published
2026-10-30
DOI
https://doi.org/10.1002/ijc.70786
Primary Topic
Cervical Cancer and HPV Research
Type
article
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article

Comparison of HPV Antibodies Measured Prior to Diagnosis of Anal, Cervical, Oropharyngeal, Penile and Vaginal Cancers in the HPV Cancer Cohort Consortium

Sylvia W Wassertheil-Smoller, Qiuyin Cai, Graham G. Giles, Gypsyamber DʼSouza et al.
International Journal of Cancer
Cervical Cancer and HPV Research
article

Comparison of HPV Antibodies Measured Prior to Diagnosis of Anal, Cervical, Oropharyngeal, Penile and Vaginal Cancers in the HPV Cancer Cohort Consortium

Sylvia W Wassertheil-Smoller, Qiuyin Cai, Graham G. Giles, Gypsyamber DʼSouza, Aimée R. Kreimer, Demetrius Albanes, Stephanie J. Weinstein, Ilir Agalliu, Allan Hildesheim, Lesley Fels Tinker, Hilary A. Robbins, Aida Ferreiro-Iglesias, Nicolas F. Schlecht, Mari Nygård, Eivind Ness‐Jensen, Gary M. Clifford, Hilde Langseth, Giske Ursin, Tim Waterboer, Justina Ucheojor Onwuka, Kala Visvanathan, Neal D. Freedman, Kristian Hveem, Wen‐Yi Huang, Lea Schroeder, Roger L. Milne, Mattias Johansson, Wei Zheng, Marie‐Pierre Nobels
article en

Abstract

Antibodies against HPV proteins can provide pre-diagnostic information about cancer development. We described the prevalence of antibodies to proteins of oncogenic HPV types prior to diagnosis of HPV-related cancers. We analysed pre-diagnostic blood from 1700 participants with incident HPV-related cancers (anal = 387, cervical = 274, oropharyngeal = 788, penile = 168, vaginal = 83) and 6221 controls from nine prospective cohorts in Europe, North America and Australia in the HPV Cancer Cohort Consortium. We measured antibodies against E6, E7 and L1 proteins for 6 HPV types, and additionally against E1, E2, E4, E6, E7 and L1 proteins of HPV16 and 18. We described seroprevalence by lead time from blood draw to cancer diagnosis (range: 0-43 years). We found that among oropharyngeal cancers, seroprevalence increased approaching diagnosis for HPV16 E1, E2, E4, E6, E7, L1 and HPV18 E1, E2, L1 (HPV16-E6: from 10.4% at > 20 years to 35.8% at 0-5 years, vs. 0.3% in controls). Anal cancer showed similar patterns for HPV16 E1, E2, E4, E6 and L1 and HPV18 E2 (HPV16-E6: from 3.8% at > 20 years to 29.8% at 0-5 years). No trends were observed for cervical, penile, or vaginal cancers. In a multivariable model fit among cases, HPV16-E6 seropositivity was higher at shorter lead times and more recent calendar periods, lower among US non-Hispanic Blacks, and varied by cancer type (highest in oropharyngeal followed by anal, vaginal, penile and cervical) (all p < 0.03). In conclusion, pre-diagnostic HPV antibody responses vary by cancer type, with seroprevalence of 6-9 HPV proteins increasing approaching diagnosis for oropharyngeal and anal cancers, but not cervical, penile or vaginal cancers.

International Journal of Cancer
Roswell Park Comprehensive Cancer Center (US), National Institutes of Health (US), Albert Einstein College of Medicine (US), Norwegian Institute of Public Health (NO), Montefiore Medical Center (US), Johns Hopkins University (US), The University of Melbourne (AU), German Cancer Research Center (DE), University of Oslo (NO), Cancer Council Victoria (AU), Norwegian University of Science and Technology (NO), Fred Hutch Cancer Center (US), St Olav's University Hospital (NO), Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud (CR), Monash Health (AU), Cancer Registry of Norway (NO), National Cancer Institute (US), Women's Health Initiative (US), Centre international de recherche sur le cancer (FR), Vanderbilt-Ingram Cancer Center (US), Division of Cancer Epidemiology and Genetics (US), Imperial College London (GB), Monash University (AU), University at Buffalo, State University of New York (US), Vanderbilt University Medical Center (US)
Openalex Percentile: Top 12%
Cervical Cancer and HPV Research
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