Human papillomavirus (HPV) DNA has been detected in the great majority of c
ancers of the uterine cervix and anus, whereas the association of HPV DNA w
ith cancer at other anogenital sites has produced less consistent results,
This study was designed to compare HPV exposure among anogenital cancer cas
es and matched controls, Cases (1782) of anogenital cancer diagnosed in the
Seattle area from 1978 to 1998 were identified and interviewed, Their resp
onses were compared with those of 2383 age- and sex-matched controls, Blood
was drawn at interview from both cases and controls and tested fur antibod
ies to HPV-16 and HPV-18, Tissue blocks were tested for HPV DNA for 649 cas
es, Serum antibodies to HPV-16 were associated with in situ and invasive ca
ncer at all sites among men and women with the exception of in situ penile
cancer. Anti-HPV-18 antibodies were associated with cancers at all sites am
ong women. The increased risk of cancer associated with HPV-16 seropositivi
ty ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for aden
ocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-
10.3) for anal canter in men. Associations between seroprevalence and cance
rs were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-pos
itive cases. HPV DNA was detected in >80% of cancers from all sites tested,
HPV-16 DNA was the type most frequently detected at all sites (range, 40.9
-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix
but detected much less often (2.6-18.1%) at other sites. These findings sup
port an important role fur HPV infection in anogenital cancer at all sites.
Differences in the proportion of seropositives among HPV-16 DNA-positive c
ases by site suggest either that the immune response varies by site or that
cancer development may lead to changes in antibody responses in a site-spe
cific fashion.