Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study.
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.
Herrero
Rolando
R
International Agency for Research on Cancer, Lyon, France. rherrero@ amnet.co.cr
Castellsagué
Xavier
X
Pawlita
Michael
M
Lissowska
Jolanta
J
Kee
Frank
F
Balaram
Prabda
P
Rajkumar
Thangarajan
T
Sridhar
Hema
H
Rose
Barbara
B
Pintos
Javier
J
Fernández
Leticia
L
Idris
Ali
A
Sánchez
María José
MJ
Nieto
Adoración
A
Talamini
Renato
R
Tavani
Alessandra
A
Bosch
F Xavier
FX
Reidel
Ulrich
U
Snijders
Peter J F
PJ
Meijer
Chris J L M
CJ
Viscidi
Raphael
R
Muñoz
Nubia
N
Franceschi
Silvia
S
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
D000914:Antibodies, Viral; D004279:DNA, Viral