Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study

BMJ 1996;312:537-539 (2 March)

Papers

Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study

Matti Lehtinen, senior research fellow,^a Joakim Dillner, senior investigator,^b Paul Knekt, senior scientist,^c Tapio Luostarinen, research fellow,^d Arpo Aromaa, director of medical research,^c Reinhard Kirnbauer, senior research fellow,^e Pentti Koskela, senior scientist,^a Jorma Paavonen, associate professor of obstetrics and gynaecology,^f Richard Peto, professor of medical statistics,^g John T Schiller, senior investigator,^h Matti Hakama, professor of epidemiology ⁱ

^a National Public Health Institute, Helsinki and Oulu, Finland, ^b Microbiology and Tumorbiology Centre, Karolinska Institute, Sweden, ^c Research and Development Centre, Social Insurance Institution, Helsinki, Finland, ^d Finnish Cancer Registry, Helsinki, Finland, ^e Department of Immunodermatology, University of Vienna Medical School, Vienna, Austria, ^f University of Helsinki, Finland, ^g Clinical Trial Service Unit and ICRF Cancer Studies Unit, University of Oxford, Oxford, ^h Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, maryland, United States, ⁱ Tampere School of Public Health, University of Tampere, Tampere, Finland

Correspondence to: Dr Lehtinen, Department of Chronic Viral Diseases, NPHI, Mannerheimintie 166, FIN-00300 Helsinki, Finland.

Abstract

Objective: To study human papillomavirus type 16 in the aetiologyof cervical carcinoma.
Design: Within a cohort of 18814 Finnish women followed forup to 23 years a nested case-control study was conducted basedon serological diagnosis of past infection with human papillomavirustype 16.
Subjects: 72 women (27 with invasive carcinoma and 45 with insitu carcinoma) and 143 matched controls were identified duringthe follow up.
Main outcome measure: Relative risk of cervical carcinoma inpresence of IgG antibodies to human papillomavirus type 16.
Results: After adjustment for smoking and for antibodies tovarious other agents of sexually transmitted disease, such asherpes simplex virus type 2 and Chlamydia trachomatis, the onlysignificant association was with infection with human papillomavirustype 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57,2P<0.001).
Conclusion: This prospective study provides epidemiologicalevidence that infection with human papillomavirus type 16 confersan excess risk for subsequent development of cervical carcinoma.

Key messages

Key messages
Human papillomavirus type 16 is the main micro-organism linked to the development of cervical cancer
Prospective studies of infection with this virus and cervical cancer have not been reported because of ethical and clinical difficulties and because diagnosis of past infections with the virus has not been possible
In this nested case-control study in over 18000 Finnish women who donated blood to a serum bank 25 years ago we were able to measure past infection with human papillomavirus type 16 with new serological tools
The results show that infection with the virus confers an increased risk of developing cervical cancer

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