Evidence map›Paper›PMID 39658222›Full record

ArticleJournal of the National Cancer Institute2025

Natural history of HPV-16 E6 serology among cancer-free men in a multicenter longitudinal cohort study.

Jaimie Z Shing, Anna R Giuliano, Nicole Brenner, Birgitta Michels, Allan Hildesheim, Sudhir Srivastava, Bradley A Sirak, John Schussler, Danping Liu, Wendy Wang and 2 more

Abstract readMulticenter Study
In one paragraph

Article in Journal of the National Cancer Institute, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jaimie Z ShingDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.ORCID 0000-0001-7064-4424
Anna R GiulianoCenter for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa, FL 33612, United States.ORCID 0000-0002-5440-8859
Nicole BrennerDivision of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Birgitta MichelsDivision of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.ORCID 0000-0001-9948-4567
Allan HildesheimDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.ORCID 0000-0003-0257-2363
Sudhir SrivastavaDivision of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0000-0002-7798-9772
Bradley A SirakCenter for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa, FL 33612, United States.ORCID 0000-0002-5089-3666
John SchusslerInformation Management Services, Silver Spring, MD 20705, United States.ORCID 0000-0002-8793-0766
Danping LiuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.ORCID 0000-0001-5483-6303
Wendy WangDivision of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Tim WaterboerDivision of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.ORCID 0000-0002-0616-6963
Aimée R KreimerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.ORCID 0000-0002-6073-2591

Funding

Natural History of HPV Infection in Men: The HIM StudyR01CA098803 · NCI · H. LEE MOFFITT CANCER CTR &RES INST · PI GIULIANO, ANNA R. · 2004 to 2014
$18.2M
Intramural Research ProgramNCI NIH HHSNIH HHSNIH HHS R01 CA098803
6 · The paper itself

Abstract

backgroundHuman papillomavirus (HPV) type 16 E6 protein seropositivity accurately predicts oropharyngeal squamous cell carcinoma risk decades before diagnosis; but the biomarker's translational potential is unknown. To inform considerations for oropharyngeal squamous cell carcinoma screening, we described HPV-16 E6 seroprevalence, predictors, and kinetics among cancer-free men.

methodsIn a cohort study in Brazil, Mexico, and the United States, we calculated HPV-16 E6 seropositivity (median fluorescence intensity > 1000), measured by multiplex serology, in cancer-free men. We assessed HPV-16 E6 seropositivity predictors using logistic regression, adjusting for country, age, sexual orientation, and lifetime number of sexual partners. Among HPV-16 E6 seropositive men, we retrieved all available retrospective serum samples and described temporal HPV-16 E6 antibody patterns.

resultsOf 3997 men, 14 had HPV-16 E6 antibodies detected (seroprevalence = 0.35%, 95% CI = 0.19% to 0.59%; median fluorescence intensity = 2407 [IQR = 1325-5986]). Older age was associated with increased odds of HPV-16 E6 seropositivity (50-84 years vs 18-29 years odds ratio = 16.61, 95% CI = 2.20 to 417.03). Serum from 11 of the 14 seropositive men retested positive; 6 men had median fluorescence intensity above 5000, of whom 2 had median fluorescence intensity greater than 10 000. Seven men had 3 or more years of follow-up; all were persistently seropositive for 3 years. One man was seropositive for 9 years but seroreverted at his exit visit. Oral HPV-16 DNA (prevalence = 1.13%) was associated with HPV-16 E6 seropositivity (odds ratio = 16.87, 95% CI = 3.35 to 69.55), but oral HPV-16 DNA positivity was not persistent over follow-up, even when HPV-16 E6 antibodies were persistently detected.

conclusionAlthough HPV-16 E6 seropositivity is rare, it is generally stable once detected; thus, HPV-16 E6 antibodies may be an informative biomarker of HPV-driven oropharyngeal squamous cell carcinoma. Few men seroreverted following HPV-16 E6 seropositivity but remained close to the seropositivity cutoff; thus, cancer risk among these men is less clear.

Indexed as

Antibodies, ViralCarcinoma, Squamous CellHuman papillomavirus 16Oncogene Proteins, ViralOropharyngeal NeoplasmsPapillomavirus InfectionsRepressor ProteinsAdultAgedBrazilHumansLongitudinal StudiesMaleMexicoMiddle AgedRetrospective StudiesAntibodies, ViralE6 protein, Human papillomavirus type 16Oncogene Proteins, ViralRepressor Proteins

Identifiers

PMID39658222
PMCPMC12058252

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.