title: Human Papillomavirus (HPV) 16 E6 seropositivity is elevated in subjects with oral HPV16 infection.
abstract: Human Papillomavirus (HPV) 16 E6 serum antibodies are common in people with HPV-related oropharyngeal cancers (HPV-OPC), but not the general population. We explored HPV16 seroprevalence in people with and without oral HPV16 infection, the cause of HPV-OPC.
  
  
  
  Oral rinse samples were collected semiannually and tested for 36 types of HPV DNA by PCR. HPV16 E6 serum antibodies were tested at the visit of first oral HPV detection in participants with prevalent (n=54), or incident (n=39) oral HPV16 DNA; or at baseline in matched participants with no oral HPV16 DNA (n=155) using multiplex serology assay. Predictors of seropositivity were examined using logistic regression.
  
  
  
  HPV16 E6 seropositivity (7.5% vs 0.7%; p=0.005) but not seropositivity to the other HPV16 antigens, was significantly more common in those with than without oral HPV16 infection. There were only 8 HPV16 E6 seropositive participants, but oral HPV16 DNA remained a strong predictor of E6 seropositivity after adjustment for other risk factors (aOR=14.6 95%CI, 1.7-122.5). Seroprevalence was similar in those with prevalent (7.4%; 4/54), and incident (7.7%; 3/39) oral HPV16 infection (p=1.00). E6 seroprevalence was associated with reduced oral HPV16 clearance, but was not statistically significant (HR=0.65 95% CI, 0.16-2.70). Seropositive participants were primarily male (87.5%), HIV-positive (75.0%; median CD4 cell-count of 840) and had oral HPV16 DNA (87.5%). History of an HPV-related cancer (0/8) or HPV-related anogenital dysplasia (1/8) was rare, and 4 participants had recent screening showing no anogenital dysplasia.
  
  
  
  HPV16 E6 seropositivity was higher among people with than without oral HPV16 infection, despite no known anogenital disease in these participants.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St., Baltimore, MD 21205, United States.
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St., Baltimore, MD 21205, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sugar
authors.affiliation: Maimonides Medical Center, 4802 Tenth Avenue, Brooklyn, NY 11219, United States.
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.affiliation: University of Pittsburgh, 3520 Fifth Avenue, Pittsburgh, PA 15213, United States.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Cranston
authors.affiliation: University of California, Los Angeles, 2-256 Factor Bldg., Los Angeles, CA 90095-1702, United States.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Wiley
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Burk
authors.affiliation: Northwestern University, 645 N Michigan Ave., Chicago, IL 60611, United States.
authors.forename: Susheel
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St., Baltimore, MD 21205, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Margolick
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, United States.
authors.forename: Howard
authors.initials: H
authors.lastname: Strickler
authors.affiliation: CORE Center at John H. Stroger Jr. Hospital of Cook County, 2225 W Harrison St., Chicago, IL 60612, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Weber
authors.affiliation: Ohio State University Comprehensive Cancer Center, 420 W 12th Ave., Columbus, OH 43210, United States.
authors.forename: Maura
authors.initials: M
authors.lastname: Gillison
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St., Baltimore, MD 21205, United States. Electronic address: gdsouza2@jhu.edu.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D009959:Oropharyngeal Neoplasms; D027383:Papillomaviridae; D030361:Papillomavirus Infections; D016036:Seroepidemiologic Studies
keywords: Antibodies; Biomarker; HPV16 E6; Oral HPV; Seroprevalence