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Type‐specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ
Author(s) -
Moberg Martin,
Gustavsson Inger,
Gyllensten Ulf
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20480
Subject(s) - viral load , medicine , cervix , dysplasia , papanicolaou stain , odds ratio , carcinoma in situ , population , human papillomavirus , cervical cancer , cervical intraepithelial neoplasia , hpv infection , gynecology , oncology , carcinoma , virology , virus , cancer , environmental health
We have previously shown that high human papillomavirus (HPV) 16 load in Papanicolaou smears negative for dysplasia is strongly associated with risk for carcinoma in situ (CIS) of the cervix. Here we study the amount of HPV DNA for some of the most frequent high‐risk HPV types as determinants of progression to cervical CIS. Real‐time PCR is used to estimate the normalized viral load of HPV 16, 18, 31, 33, 35, 39, 45, 52, 58 and 67 in 457 cases of cervical CIS and 552 matched population controls. A total of 2,747 archival Pap smears from gynecologic health examinations, collected over a period of up to 26 years, were analyzed to assess viral load during the infection history. Cervical smear samples differ widely in amount of DNA, underscoring the need for normalization of HPV load to number of cells in the sample. The risk of developing cervical CIS increases with higher viral load for most of the HPV types studied. The range of copy numbers per cell does not differ between HPV types but the odds ratio for CIS in the percentile with highest viral load is substantially higher for HPV 16 (OR = 36.9; 95% CI = 8.9–153.2) than for HPV 31 (OR = 3.2; 95% CI = 1.1–9.1) or HPV 18/45 (OR = 2.6; 95% CI = 1.0–6.4). Therefore, HPV viral load may be predictive of future risk of cervical CIS at a stage when smears are negative for squamous abnormalities, but differences between HPV types need closer attention. © 2004 Wiley‐Liss, Inc.