Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ:: a nested case-control study

被引:256
作者
Ylitalo, N
Sorensen, P
Josefsson, AM
Magnusson, PKE
Andersen, PK
Pontén, J
Adami, HO
Gyllensten, UB
Melbye, M
机构
[1] Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden
[2] Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark
[3] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden
[4] Univ Copenhagen, Dept Biostat, Copenhagen, Denmark
[5] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA
[6] Harvard Univ, Harvard Ctr Canc Prevent, Boston, MA 02115 USA
关键词
D O I
10.1016/S0140-6736(00)02402-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Persistent infection with certain types of human papillomavirus (HPV) is believed to be a prerequisite for the development of cervical neoplasia. Persistence may depend on certain characteristics, such as viral load, which has so far been given little attention. We investigated the association between HPV 16 viral load and cervical carcinoma in situ. Methods We did a nested case-control study of women participating in cytological screening in Sweden. We used a sensitive quantitative PCR assay to estimate HPV 16 load in multiple smears for each woman, taken during a period of up to 26 years before diagnosis. We calculated C-t values, which decrease as the number of viral DNA copies increases. Findings 2081 smears from 478 cases and 1754 smears from 608 controls were tested. Among cases, we found a consistently increased load of HPV 16 already 13 years or more before diagnosis, and when many smears were still cytologically normal. Women with high HPV 16 viral loads were at least 30 times the relative risk of HPV-16-negative women more than a decade before diagnosis. The increase in relative risk was constant over time. About 25% of women (95% CI 0.12-0.32) infected with a high viral load before age 25 years developed cervical carcinoma in situ within 15 years. Interpretation Cervical carcinoma in situ associated with HPV 16 occurs mainly in HPV-16-positive women who have consistently high viral loads long term. Women at high risk could be identified by use of a quantitative HPV test in addition to cytological screening.
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页码:2194 / 2198
页数:5
相关论文
共 35 条
  • [1] PREVALENCE OF HUMAN PAPILLOMAVIRUS IN CERVICAL-CANCER - A WORLDWIDE PERSPECTIVE
    BOSCH, FX
    MANOS, MM
    MUNOZ, N
    SHERMAN, M
    JANSEN, AM
    PETO, J
    SCHIFFMAN, MH
    MORENO, V
    KURMAN, R
    SHAH, KV
    ALIHONOU, E
    BAYO, S
    MOKHTAR, HC
    CHICAREON, S
    DAUDT, A
    DELOSRIOS, E
    GHADIRIAN, P
    KITINYA, JN
    KOULIBALY, M
    NGELANGEL, C
    TINTORE, LMP
    RIOSDALENZ, JL
    SARJADI
    SCHNEIDER, A
    TAFUR, L
    TEYSSIE, AR
    ROLON, PA
    TORROELLA, M
    TAPIA, AV
    WABINGA, HR
    ZATONSKI, W
    SYLLA, B
    VIZCAINO, P
    MAGNIN, D
    KALDOR, J
    GREER, C
    WHEELER, C
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1995, 87 (11): : 796 - 802
  • [2] Determinants of persistent detection of human papillomavirus DNA in the uterine cervix
    Brisson, J
    Bairati, I
    Morin, C
    Fortier, M
    Bouchard, C
    Christen, A
    Bernard, P
    Roy, M
    Meisels, A
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1996, 173 (04) : 794 - 799
  • [3] CHUA KL, 1995, ANAL QUANT CYTOL, V17, P221
  • [4] Cuzick J, 1997, NEW DEVELOPMENTS IN CERVICAL CANCER SCREENING AND PREVENTION, P364
  • [5] HUMAN PAPILLOMAVIRUS TYPE-16 DNA IN CERVICAL SMEARS AS PREDICTOR OF HIGH-GRADE CERVICAL-CANCER
    CUZICK, J
    TERRY, G
    HO, L
    HOLLINGWORTH, T
    ANDERSON, M
    [J]. LANCET, 1992, 339 (8799) : 959 - 960
  • [6] TYPE-SPECIFIC HUMAN PAPILLOMAVIRUS DNA IN ABNORMAL SMEARS AS A PREDICTOR OF HIGH-GRADE CERVICAL INTRAEPITHELIAL NEOPLASIA
    CUZICK, J
    TERRY, G
    HO, L
    HOLLINGWORTH, T
    ANDERSON, M
    [J]. BRITISH JOURNAL OF CANCER, 1994, 69 (01) : 167 - 171
  • [7] Cuzick J, 1997, NEW DEVELOPMENTS IN CERVICAL CANCER SCREENING AND PREVENTION, P373
  • [8] EFFICIENCY OF ORGANIZED AND OPPORTUNISTIC CYTOLOGICAL SCREENING FOR CANCER IN-SITU OF THE CERVIX
    GUSTAFSSON, L
    SPAREN, P
    GUSTAFSSON, M
    WILANDER, E
    BERGSTROM, R
    ADAMI, HO
    [J]. BRITISH JOURNAL OF CANCER, 1995, 72 (02) : 498 - 505
  • [9] Real time quantitative PCR
    Heid, CA
    Stevens, J
    Livak, KJ
    Williams, PM
    [J]. GENOME RESEARCH, 1996, 6 (10): : 986 - 994
  • [10] Ho GYF, 1998, INT J CANCER, V78, P594, DOI 10.1002/(SICI)1097-0215(19981123)78:5&lt