High-risk human papillomavirus associated with incident cervical intraepithelial neoplasia developing in mothers in the Finnish Family HPV Study cohort

Abstract

Background: Cofactors of high-risk (HR) human papillomavirus (HPV) in the progression of cervical intraepithelial neoplasia (CIN) are incompletely characterized. In this study these cofactors were investigated in a longitudinal setting. Methods: A cohort of 329 women (mean age 25.5 y) were enrolled in the Finnish Family HPV Study, and followed-up for 6 y with serial cervical samples for HPV genotyping, virus integration status, and HPV serology. Hospital records were reviewed until March 2010 and linked with HPV detection data. All incident CIN lesions were subjected to HPV genotyping. HPV covariates were studied in an age- and HPV-matched nested case–control (1:4) setting. Results: Twelve of the 329 women developed an incident CIN: 2 CIN1, 3 CIN2, and 7 CIN3. HPV16 was detected most frequently (7/12), followed by HPV58 (2/12), HPV18, HPV31, and HPV42. HPV integration was present in 4/12 cases. Long-lasting persistence of HPV31 and HPV16 preceded incident CIN2 and CIN3. In multivariate conditional logistic regression, the risk for incident CIN increased up to 4-fold with increasing number of deliveries (p = 0.024) and decreased with history of genital warts (p = 0.036). Conclusion: Baseline HR-HPV infections and their persistence precede incident CIN by several years. The 2 independent covariates of HR-HPV were (1) number of deliveries (increasing the risk), and (2) history of genital warts (protective effect).

Keywords::

• CIN
• incident
• HPV
• genotypes
• serology

Acknowledgements

The authors express their special thanks to Dr Tim Waterboer and Dr Michael Pawlita (Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Centre; DKFZ), Heidelberg, Germany, who have conducted all the multiplex HPV serology analyses for this whole cohort. The skilful technical assistance of Tatjana Peskova, Mariia Henttinen and Ketlin Adel is gratefully acknowledged.

Declaration of interest: The authors of this study do not have commercial or other association that may lead to a conflict of interest. This study has been supported by the Academy of Finland, Helsinki, Finland; Cancer Society of Finland, Helsinki, Finland; Päivikki and Sakari Sohlberg Foundation, Helsinki, Finland; the Government Special Foundation (EVO) for Turku University Hospital, Turku, Finland; and South-Western Division of Finnish Cancer Foundation, Turku, Finland.