Epidemiologic classification of human papillomavirus types associated with cervical cancer
Authors: Chris J L M Meijer
Xavier Castellsagué
International Agency for Research on Cancer Multicenter Cervical Cancer Study Group
Keerti V Shah
Rolando Herrero
Nubia Muñoz
Silvia de Sanjosé
Peter J F Snijders
F Xavier Bosch
Journal: New England Journal of Medicine (2003)
Discipline: CLINICAL MEDICINE
Keywords: HPV; cervical cancer; risk factors; DNA detection; polymerase-chain-reaction
Affiliations: International Agency for Research on Cancer, Lyons, France. 

Abstract:  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 adequately 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. 

Retracted: No

PubPeer comments:
 Hi, Thank you for publishing this highly cited paper. In the text and Table 2, you mention HPV58 showing an increased frequency of infection with age. However, I noticed that the HPV58 frequencies are actually higher in the controls than the cases. I think this is because the sums for Table 2 are among infected women (and the number of *uninfected* women should be much higher among control), in addition to the absolute number being lower in controls (which could cause the percent of infected controls to be higher by chance). I found Table 4 to be the most helpful in noticing this. **Would it be possible for you to explain why you calculated percentages with respect to *infected* controls versus total controls in Table 2?** I guess this could help identify low-risk HPV types (with higher percentages in controls), but I found it to be kind of confusing at first. There are certainly a lot of studies citing HPV58 as a high-risk HPV type, but I am wondering if there might be something that I am missing. Thank you very much. Sincerely, Charles ,