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N Engl J Med. 2003 Feb 6;348(6):518-27.
Epidemiologic classification of human papillomavirus
types associated with cervical cancer.
Mu?z N, Bosch FX, de Sanjos?S, Herrero R, Castellsagu?
X, Shah KV, Snijders PJ, Meijer CJ; International Agency
for Research on Cancer Multicenter Cervical Cancer Study
Group.
International Agency for Research on Cancer, Lyons,
France. cris@ico.scs.es
Background:
Infection with human papilloma virus (HPV)
is the main cause of cervical cancer, but the risk
associated with the various HPV types has not been
ade quately assessed.
Methods:
We pooled data from 11
case-control studies from nine countries involving 1918
women with histologically confirmed squamous-cell
cervical cancer and 1928 control women. A common
protocol and questionnaire were used. Information on
risk factors was obtained by personal interviews, and
cervical cells were collected for detection of HPV DNA
and typing in a central laboratory by
polymerase-chain-reaction-based assays (with MY09/MY11
and GP5+/6+ primers).
Results:
HPV DNA was detected in
1739 of the 1918 patients with cervical cancer (90.7
percent) and in 259 of the 1928 control women (13.4
percent). With the GP5+/6+ primer, HPV DNA was detected
in 96.6 percent of the patients and 15.6 percent of the
controls. The most common HPV types in patients, in
descending order of Frequency, were types 16, 18, 45,
31, 33, 52, 58, and 35. Among control women, types 16,
18, 45, 31, 6, 58, 35, and 33 were the most common. For
studies using the GP5+/6+ primer, the pooled odds ratio
for cervical cancer associated with the presence of any
HPV was 158.2 (95 percent confidence interval, 113.4 to
220.6). The odds ratios were over 45 for the most common
and least common HPV types. Fifteen HPV types were
classified as high-risk types (16, 18, 31, 33, 35, 39,
45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were
classified as probable high-risk types (26, 53, and 66);
and 12 were classified as low-risk types (6, 11, 40, 42,
43, 44, 54, 61, 70, 72, 81, and CP6108). There was good
agreement between our epidemiologic classification and
the classification based on phylogenetic grouping.
Conclusions:
In addition to HPV types 16 and 18, types
31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82
should be considered carcinogenic, or high-risk, types,
and types 26, 53, and 66 should be considered probably
carcinogenic.
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