title: Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study.
abstract: BACKGROUND
  Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries.
  
  
  METHODS
  We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons.
  
  
  RESULTS
  HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oropharynx (OR = 9.2, 95% CI = 4.8 to 17.7).
  
  
  CONCLUSIONS
  HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.
authors.affiliation: International Agency for Research on Cancer, Lyon, France. rherrero@ amnet.co.cr
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Xavier
authors.initials: X
authors.lastname: Castellsagué
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
authors.forename: Prabda
authors.initials: P
authors.lastname: Balaram
authors.forename: Thangarajan
authors.initials: T
authors.lastname: Rajkumar
authors.forename: Hema
authors.initials: H
authors.lastname: Sridhar
authors.forename: Barbara
authors.initials: B
authors.lastname: Rose
authors.forename: Javier
authors.initials: J
authors.lastname: Pintos
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernández
authors.forename: Ali
authors.initials: A
authors.lastname: Idris
authors.forename: María José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Adoración
authors.initials: A
authors.lastname: Nieto
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tavani
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Reidel
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Raphael
authors.initials: R
authors.lastname: Viscidi
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007391:International Cooperation; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012725:Sexual Behavior; D012907:Smoking / Q000009:adverse effects; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral