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Prospective study of human papillomavirus and risk of cervical adenocarcinoma
Author(s) -
Dahlström Lisen Arnheim,
Ylitalo Nathalie,
Sundström Karin,
Palmgren Juni,
Ploner Alexander,
Eloranta Sandra,
Sanjeevi Carani B.,
Andersson Sonia,
Rohan Thomas,
Dillner Joakim,
Adami HansOlov,
Sparén Pär
Publication year - 2010
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.25408
Subject(s) - adenocarcinoma , medicine , odds ratio , cervical cancer , population , oncology , prospective cohort study , cancer , gynecology , environmental health
Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population‐based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow‐up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6–46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8–66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5–192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8–206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.