Prospective study of human papillomavirus and risk of cervical adenocarcinoma

• Published in: International journal of cancer Vol. 127; no. 8; pp. 1923 - 1930
• Main Authors: Dahlström, Lisen Arnheim, Ylitalo, Nathalie, Sundström, Karin, Palmgren, Juni, Ploner, Alexander, Eloranta, Sandra, Sanjeevi, Carani B., Andersson, Sonia, Rohan, Thomas, Dillner, Joakim, Adami, Hans‐Olov, Sparén, Pär
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.10.2010; Wiley-Blackwell
• Subjects: 80 and over; Adenocarcinoma; Adenocarcinoma - pathology; Adenocarcinoma - virology; adenocarcinoma in situ; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cancer and Oncology; Cancer och onkologi; Carcinoma in Situ; Carcinoma in Situ - pathology; Carcinoma in Situ - virology; Case-Control Studies; cervical cancer; classification; Clinical Medicine; DNA; DNA, Viral - genetics; Female; Follow-Up Studies; genetics; HPV; Humans; Infectious diseases; isolation & purification; Klinisk medicin; MATEMATIK; MATHEMATICS; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neoplasm Invasiveness; Papillomaviridae; Papillomaviridae - classification; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomavirus Infections; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; pathology; Prognosis; prospective; Prospective Studies; Risk Factors; Sweden; Tumors; Uterine Cervical Neoplasms; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Viral; Viral diseases; virology; Young Adult; Sweden; adenocarcinoma in situ; In situ; adenocarcinoma; Papovaviridae; Malignant tumor; Female genital diseases; HPV; Infection; Papillomavirus; Virus; Prospective; Human papillomavirus; Cancerology; Viral disease; Risk factor; Cervical adenocarcinoma; Uterine cervix diseases; Cervical cancer; Cancer
• DOI: 10.1002/ijc.25408
• ISSN: 0020-7136; 1097-0215

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.