A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears
Keng-Ling Chua
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorFredrik Wiklund
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorPer Lenner
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorTord Ångström
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorGöran Hallmans
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorFrank Bergman
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorMartin Sapp
Department of Medical Microbiology, University of Mainz, Germany
Search for more papers by this authorJohn Schiller
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, USA
Search for more papers by this authorGöran Wadell
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorAnders Hjerpe
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorCorresponding Author
Joakim Dillner
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden
Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden. Fax: +46-8-32 67 02Search for more papers by this authorKeng-Ling Chua
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorFredrik Wiklund
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorPer Lenner
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorTord Ångström
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorGöran Hallmans
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorFrank Bergman
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorMartin Sapp
Department of Medical Microbiology, University of Mainz, Germany
Search for more papers by this authorJohn Schiller
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, USA
Search for more papers by this authorGöran Wadell
Departments of Oncology, Clinical Cytology, Nutritional Research, Pathology and Virology, Umeå University, Umeå, Sweden
Search for more papers by this authorAnders Hjerpe
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorCorresponding Author
Joakim Dillner
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden
Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden. Fax: +46-8-32 67 02Search for more papers by this authorAbstract
To estimate the risk of developing cervical intra-epithelial neoplasia (CIN) among women exposed to human papillomavirus (HPV) type 16, we performed a prospective study in a population-based cohort of more than 15,000 women followed for 34.9 months. Seventy-four women developed CIN during follow-up and were matched for age, time of sampling and area of residence with 148 women who remained CIN-free during follow-up. The blood samples taken at enrollment were tested for serum antibodies to HPV types 16, 18 and 33 capsids. Cervical smears or biopsies were analyzed for the presence of HPV DNA by nested PCR using HPV general primers and by HPV 16- and 18-type-specific PCR. HPV serology and HPV-PCR were in good agreement, particularly when the blood sample and the Pap smear were taken less than 6 months apart. HPV DNA was found in 88% of cases and 4% of controls, whereas HPV 16 DNA was present in 44% of cases and in 1 of 142 controls. HPV-16-seropositive women had a 3-fold increased risk of developing CIN. The risk was highest among women younger than 35 years of age, of whom an estimated 3.4% of HPV-16-seropositive and 0.5% of seronegative women developed CIN. Since the risk associated with HPV-16 seropositivity (a measure of past or present infection) was 35-fold lower than that of HPV DNA (present infection), most infections appear to be eliminated before CIN develops. In conclusion, HPV 16 infection does confer an excess risk of CIN development, and HPV DNA detection has a high predictive value for the presence of high-grade CIN. © 1996 Wiley-Liss, Inc.
References
- Andersson-Ellstrom, A., Dillner, J., Hagmar, B., Schiller, J., Sapp, M., Forssman, L. and Milsom, I., Comparison of development of serum antibodies to HPV 16 and HPV 33 and acquisition of cervical HPV DNA among sexually experienced and virginal young girls. A longitudinal cohort study. Sex. transm. Dis., 23, 234–238 (1996).
- Chua, K. L. and Hjerpe, A., Polymerase-chain-reaction (PCR) analysis of human papillomavirus (HPV) in archival smears. Anal. quant Cytol. Histol., 17, 221–229 (1995).
-
Chua, K. L. and
Hjerpe, A.,
Persistence of human-papillomavirus (HPV) infections preceding cervical carcinoma.
Cancer,
77, 121–127
(1996).
10.1002/(SICI)1097-0142(19960101)77:1<121::AID-CNCR20>3.0.CO;2-6 CAS PubMed Web of Science® Google Scholar
- De Roda Husman, A-M., Snijders, P. J. F., Stel, H. V., Van Den Brule, A. J. C., Meijer, C. J. L. M., and Walboomers, J. M. M., Processing of logn stored archival cervical smears for human-papillomavirus detection by the polymerase chain reaction. Brit. J. Cancer, 72, 412–417 (1995a).
- De Roda Husman, A-M., Walboomers, J. M. M., Van den Brule, A. J. C., Meijer, C. J. L. M., and Snijders, P. J. F., The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human-papillomavirus detection by PCR. Gen. VroL, 76, 1057–1062 (1995b).
- Dillner, J., Serology of human papillomavirus. Cancer J., 8, 264–269 (1995).
- Dillner, J., Kallings, I., Brihmer, C., Sikstrom, B., Koskela, P., Lehtinen, M., Schiller, J. T., Sapp, M. and Mardh, P. A., Seropositivity to human papillomavirus types 16, 18 or 33 capsids and to chlamydia trachomatis are markers of sexual behaviour. J. infect Dis., 173, 1394–1398 (1996)
- Dillner, J., Lenner, P., Lehtinen, M., Eklund, C., Heino, P., Wiklund, F., Hallmans, G. and Stendahl, U., A population-basedsero-epidemiological study of cervical cancer. Cancer Res., 54, 134–141 (1994).
- Dillner, J., Wiklund, F., Lenner, P., Eklund, C., Fredriksson Shanazarian, V., Schiller, J. T., Hibma, M., Hallmans, G. and, Stendahi, U., Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer. Int. J. Cancer, 60, 377–382 (1995).
- Evander, M., Boden, E., Bjersing, L., Rylander, E. and Wadell, G., Oligonucleotide primers for DNA amplification of the early regions 1, 6 and 7 from human papillomavirus types 6, 11, 16, 18, 31 and 33. Arch. Virol., 116, 221–233 (1991).
- Evander, M., Edlund, K., Boden, E., Gustafsson, A., Jonsson, M., Karlsson, R., Rylander, E. and Wadell, G., Comparison of a one-step and a two-step Polymerase chain reaction with degenerate general primers in a population-based study of human-papillomavirus infection in young Swedish in young Swedish women. J. clin. Microbiol, 30, 987–992 (1992).
- Evander, M., Edlund, K., Gustafsson, A., Jonsson, M., Karlsson, R., Rylander, E. and Wadell, G., Human-papillomavirus infection is transient in young women: a population-based cohort study. J. infect. Dis., 171, 1026–1030 (1995).
- Fleiss, J. L., Statistical methods for the rates and proportions, pp. 143–147, John Wiley, New York (1973).
- Heino, P., Eklund, C., Fredriksson-Shahnazarian, V., Goldman, S., Schiller, J. T. and Dill, J., Association of serum IgG antibodies against human-apillomavirus-type-16 capsids with anal epidemoid carcinoma. J. nat. cancer Inst., 87, 437–440 (1995).
- Hildesheim, A., Schiffman, M. H., Gravitt, P. E., Glass, A. G., Greer, C. E., Zhang, T., Scott, D. R., Rush, B. B., Lawler, P. and Sherman, M. E., Persistence of type-specific human-papillomavirus infection among cytologically normal women. J. infct. Dis., 169, 235–240 (1994).
- Ho, G. Y., Burk, R. D., Klein, S., Kadish, A. S., Chang, C. J., Palan, P., Basu, J., Tachezy, R., Lewis, R. and Romney, S., Persistent genital human-papillomavirus infection as a risk factor for persistent cervical dysplasia. J. nat. Cancer Inst., 87, 1365–1371 (1995).
- Kirnbauer, R., Hubbert, N. L., Wheller, C. M., Becker, T. M., Low, D. R. and Schiller, J. T., A virus-like particle ELISA detects serum antibodies in a majority of women infected with human papillomavirus type 16. J. nat. Cancer Inst., 86, 494–498 (1994).
- Kirnbauer, R., Taub, J., Greenstone, H., Roden, R., Durst, M., Gissmann, L., Lowy, D. R. and Schiller, J. T., Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J. Virol., 67, 6929–6936 (1993).
- L. G. Koss (ed.), Diagnostic cytology and its histopathologic basis, 3rd ed., Lippincott, Philadelphia, Toronto (1979).
- Ley, C., Bauer, H. M., Reingold, A., Schiffman, M. H., Chambers, J. C., Tashiro, C. J. and Manos, M. M., Determinants of genital human-papillomavirus infection in young women. J. nat. Cancer Inst. 83, 997–1003 (1991).
- Melkert, P. W., Hopman, E., Van den Brule, A. J., Risse, E. K., Van Diest, P. J., Bleker, O. P., Helmerhorst, T., Schipper, M. E., Meijer, C. J. and Walboomers, J. M., Presence of HPV in cytomorphologi cally normal cervical smears, as determined by the Polymerase chain reaction, is age-dependent. Int. J. Cancer, 53, 919–923 (1993).
- Nasiell, K., Nasiell, M. and Vaclavinkova, V., Behaviour of moderate cervical dysplasia during long-term follow-up. Obstet. Gynecol., 61, 609–614 (1983).
- Rhoads, D. D., Dixit, A. and Roufa, D. J., Primary structure of human ribosomal protein S14 and the gene that encodes it. Mol. cell. Biol., 6, 2774–2783 (1986).
- Schiffman, M. H., Recent progress in defining the epidemiology of human-papillomavirus infection and cervical neoplasia. J. nat. Cancer Inst., 84, 394–398 (1992).
- Schiffman, M. H., Bauer, H. M., Hoover, R. N., Glass, A. G., Cadell, D. M., Rush, B. B., Scott, D. R., Sherman, M. E., Kurman, R. J., Wacholder, S., Stanton, C. K. and Manos, M. M., Epidemiologic evidence showing that human-papillomavirus infection causes most cervical intra-epithelial neoplasia. J. nat. Cancer Inst., 85, 959–964 (1993).
-
Ting, Y. and
Manos, M. M.,
Detection and typing of genital human papillomavirus
In: (Eds., M. A. Innis,
D. H. Gelfand,
J. J. Sninsky and
T. J. White)
PCR protocols: a guide to methods and applications,
pp. 356–367,
Academic Press, New York
(1990).
10.1016/B978-0-12-372180-8.50046-9 Google Scholar
- Volpers, C., Schirmacher, P., Streeck, R. E. and Sapp, M., Assembly of the major and minor capsid proteins of HPV 33 into virus-like particles and tubular structures in insect cells. Virology, 200, 504–512 (1994).
- Walboomers, J. M. M., De Roda Husman, A-M., Snijders, P. J. F., Stel, H. V., Risse, E. K. J., Helmerhorst, T. J. M., Voorhorst, F. J. and Meijer, C. J. L. M., Human papillomavirus in false-negative archival cervical smears: implications for screening for cervical cancer. J. Clin. Pathol., 48, 728–732 (1995).
- Wikstrom, A., Van Doornum, G. J. J., Quint, W. G. V., Schiller, J. T. and Dillner, J., Identification of human-papillomavirus seroconver-sions. J. gen. Virol., 76, 529–539 (1995).
- Zur Hausen, H., Viruses in human cancers. Science, 254, 1167–1173 (1991).
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