title: Prospective study of human papillomavirus and risk of cervical adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. lisen.arnheim.dahlstrom@ki.se
authors.forename: Lisen Arnheim
authors.initials: LA
authors.lastname: Dahlström
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ylitalo
authors.forename: Karin
authors.initials: K
authors.lastname: Sundström
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.forename: Sandra
authors.initials: S
authors.lastname: Eloranta
authors.forename: Carani B
authors.initials: CB
authors.lastname: Sanjeevi
authors.forename: Sonia
authors.initials: S
authors.lastname: Andersson
authors.forename: Thomas
authors.initials: T
authors.lastname: Rohan
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Pär
authors.initials: P
authors.lastname: Sparén
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral
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